tag:theconversation.com,2011:/global/topics/embryo-2837/articlesEmbryo – The Conversation2024-03-08T13:36:46Ztag:theconversation.com,2011:article/2232672024-03-08T13:36:46Z2024-03-08T13:36:46ZRare access to hammerhead shark embryos reveals secrets of its unique head development<figure><img src="https://images.theconversation.com/files/575205/original/file-20240213-26-2257zy.jpeg?ixlib=rb-1.1.0&rect=558%2C0%2C9359%2C6223&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The characteristic hammer-shaped head is just becoming visible in this image of an embryonic bonnethead shark. Scale bar = 1 cm.</span> <span class="attribution"><span class="source">Steven Byrum and Gareth Fraser, Department of Biology, University of Florida</span></span></figcaption></figure><p>Scientists very rarely get access to most sharks, the development of their young or the nursery grounds where they grow. So seeing a <a href="https://www.floridamuseum.ufl.edu/discover-fish/species-profiles/sphyrna-tiburo/">hammerhead shark</a> (<em>Sphyrna tiburo</em>) embryo, halfway through its five-month development, is very unusual.</p>
<p>Access to growing embryos is key for <a href="https://scholar.google.com/citations?user=J5qu-2gAAAAJ&hl=en&oi=ao">developmental biologists like me</a> as we try to understand the diversity of animals on Earth. Usually the fishes I study, including other shark species, lay eggs, which allows us to easily watch development in real time.</p>
<p>Hammerhead sharks don’t lay eggs, though. They gestate their pups in utero. A pregnant shark carries up to 16 embryos, each nourished by an umbilical cord, just like human embryos are. Then the mother gives birth to live young, and these babies are self-sufficient with teeth and jaws, ready to survive on their own.</p>
<p>Access to a hammerhead embryo is very rare, which is what makes this image so special.</p>
<h2>Access to a very rare resource</h2>
<p>In order to make this image, my colleagues and I salvaged embryos from adult female sharks that had been caught as part of population surveys off both the Gulf and Atlantic coasts of Florida. Usually these sharks are tagged and released. But a small number die during this process and are then studied for insights about diet, age, growth, reproduction and toxicology. No sharks were sacrificed just for our study. The embryos would have otherwise been wasted when the mothers died.</p>
<p>For this work, <a href="https://scholar.google.com/citations?user=GAE2Hi8AAAAJ&hl=en">Steven Byrum</a>, a graduate student <a href="https://www.fraser-lab.net/">in my lab</a>, was able to <a href="https://doi.org/10.1002/dvdy.658">document the entire set of developmental stages</a> using a total of 177 bonnethead shark embryos.</p>
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<a href="https://images.theconversation.com/files/579899/original/file-20240305-20-2yce7q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="composite image of six shark embryos at advancing stages of development" src="https://images.theconversation.com/files/579899/original/file-20240305-20-2yce7q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/579899/original/file-20240305-20-2yce7q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=849&fit=crop&dpr=1 600w, https://images.theconversation.com/files/579899/original/file-20240305-20-2yce7q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=849&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/579899/original/file-20240305-20-2yce7q.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=849&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/579899/original/file-20240305-20-2yce7q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1067&fit=crop&dpr=1 754w, https://images.theconversation.com/files/579899/original/file-20240305-20-2yce7q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1067&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/579899/original/file-20240305-20-2yce7q.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1067&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Images of embryos of different ages reveal how the sharks develop in utero.</span>
<span class="attribution"><span class="source">Steven Byrum and Gareth Fraser, Department of Biology, University of Florida</span></span>
</figcaption>
</figure>
<p>We were able to assemble a kind of visual growth chart, from the earliest embryos – they look nothing like hammerheads – to the specific point in development when the hammerhead takes shape, through the rest of development before birth. No scientists had ever before charted the development of hammerhead sharks in this way.</p>
<p>This research allows us to study crucial stages in hammerhead development and, importantly, the precise moments – like this one pictured – when the embryo develops the characteristic head shape.</p>
<h2>Adding to what’s known about hammerheads</h2>
<p>Hammerheads are a peculiar group of <a href="https://doi.org/10.1016/j.ympev.2010.01.037">only eight species of sharks</a> that uniquely develop a hammer-shaped head known as a cephalofoil, named for its hydrodynamic design used for <a href="https://doi.org/10.2307/1446449">quick turns and pinning down prey</a>. This particular species is known as the bonnethead because of its relatively small, rounded “hammer.” </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/579876/original/file-20240305-28-sk4tsz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="view from above of grayish fish swimming just above sandy seafloor" src="https://images.theconversation.com/files/579876/original/file-20240305-28-sk4tsz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/579876/original/file-20240305-28-sk4tsz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=395&fit=crop&dpr=1 600w, https://images.theconversation.com/files/579876/original/file-20240305-28-sk4tsz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=395&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/579876/original/file-20240305-28-sk4tsz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=395&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/579876/original/file-20240305-28-sk4tsz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=497&fit=crop&dpr=1 754w, https://images.theconversation.com/files/579876/original/file-20240305-28-sk4tsz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=497&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/579876/original/file-20240305-28-sk4tsz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=497&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A grown bonnethead shark has sensory advantages from its hammer-shaped head.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/bonnethead-shark-underwater-bahamas-west-indies-royalty-free-image/200351925-001">Tom Brakefield/Stockbyte via Getty Images</a></span>
</figcaption>
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<p>Scientists think the wide, flattened head shape with eyes on each side evolved to enhance the animals’ senses. Wide positioning of the eyes allows for an increased field of vision, and wide, expanded nasal capsules provide enhanced olfactory capability.</p>
<p>The hammer-shaped heads are covered with expanded electric detector organs that support the sharks’ “sixth sense.” They can detect even the smallest electrical signals, such as the pulses from a prey fish’s heartbeat, or the Earth’s <a href="https://doi.org/10.1098/rsif.2004.0021">magnetic fields, which they can use to navigate</a> during migration.</p>
<p>Access to these amazing shark pup embryos allows us to compare their development with other regular-headed sharks and ask how and why hammerheads grow these wonderful noggins.</p>
<p>The ocean hides a wealth of weird and wonderful fishes, most of which are inaccessible, and studies of their development are impossible. My lab continues to uncover insights into the evolution of life on Earth thanks to these fortuitous opportunities.</p><img src="https://counter.theconversation.com/content/223267/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gareth J. Fraser receives funding from the National Science Foundation. </span></em></p>Because hammerhead sharks give birth to live young, studying their embryonic development is much more complicated than harvesting some eggs and watching them develop in real time.Gareth J. Fraser, Associate Professor of Evolutionary Developmental Biology, University of FloridaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2248182024-03-01T18:10:05Z2024-03-01T18:10:05ZWhy a US state court ruling on the rights of children before birth is unjust<p>In 2020, in a medical facility in one of the southern states of the US, a patient wandered into an unsecured nursery for extremely premature children. Unfortunately, the patient managed to accidentally disconnect multiple babies from their life support. Worried that they would get in trouble, they fled the scene. But by the time the children were found, it was too late. Several had already died.</p>
<p>Of course, this event was extremely distressing for the children’s parents. They subsequently sued the medical facility, but to their astonishment, the state court rejected their case. Had the mothers been pregnant at the time of the incident, they would have had a legal claim for damages. But because the children were in the nursery – outside their mothers’ bodies, the court found that the “wrongful death” statute did not apply.</p>
<p>What should we make of this extraordinary case from the point of view of medical ethics?</p>
<p>Some readers will have realised already that the case above relates to <a href="https://publicportal-api.alappeals.gov/courts/68f021c4-6a44-4735-9a76-5360b2e8af13/cms/case/343D203A-B13D-463A-8176-C46E3AE4F695/docketentrydocuments/E3D95592-3CBE-4384-AFA6-063D4595AA1D">a judgment</a> released by <a href="https://www.theguardian.com/us-news/2024/feb/20/alabama-supreme-court-frozen-embryos-children-ruling-ivf">the Alabama Supreme Court earlier this month</a>. The case description <a href="https://www.technologyreview.com/2024/02/23/1088851/alabama-court-embryo-artificial-wombs/">reflects the facts</a>, but perhaps I should clarify.</p>
<p>The nursery was not a newborn intensive care unit, but a <a href="https://www.statnews.com/2024/02/22/alabama-ivf-ruling-science-translocation-fertilized-embryos/">“cryogenic nursery”</a>. The extremely premature children were not 23 weeks gestation, but embryos three to seven days after conception – smaller than a grain of salt. </p>
<p>The wandering patient had removed the embryos from the freezer and dropped them after burning his hand. In a ruling that many have claimed has disturbing implications for fertility treatment, the court found that the parents in the case could sue the medical facility for the death of their unborn children.</p>
<h2>Old laws, new technology</h2>
<p>There are different responses that might be made to the Alabama Supreme Court judgment. For example, we might question whether the court should have applied a <a href="https://law.justia.com/codes/alabama/2022/title-6/chapter-5/article-22/section-6-5-391/">150-year-old piece of Alabama law</a> to a late 20th-century reproductive technology. The lawmakers in 1872 clearly did not have a case like this in mind. </p>
<p>The dissenting judge in the case, Justice Cook, <a href="https://www.nytimes.com/interactive/2024/02/21/us/alabama-supreme-court-embryo-ruling.html">argued</a> that when this law was enacted there was no intention for it to be applied to foetuses, let alone embryos.</p>
<p>Alternatively, we might ask how this ruling applies to IVF more generally. IVF providers in Alabama have apparently <a href="https://www.wsj.com/politics/alabama-ivf-gop-rushes-to-pass-protections-be65fa9c">paused activity</a>, worried that they might become criminally liable if they dispose of unwanted frozen embryos. Many commentators have <a href="https://apnews.com/article/embryos-ivf-abortion-personhood-laws-ffe4f4d326469a97fef999254ca86eea">expressed deep concern</a> about how this ruling might be taken up by campaigners and politicians to further restrict reproductive choice.</p>
<p>But from an ethical perspective, the court did three things that were unquestionably correct. First, it recognised that the parents in this case had suffered a significant loss for which they were owed redress. This loss is more than just a breach of contract. The clinic’s apparent negligence had deprived these parents of future children.</p>
<p>Second, the court recognised that the physical location of an embryo cannot change its intrinsic moral properties. If parents would have had a claim for loss of a five-day-old embryo in the womb, it makes no ethical sense to say that they would have no claim for loss of an embryo that happens to be residing in a freezer.</p>
<p>Third, from a biological point of view, the Alabama Supreme Court was correct to identify these embryos as living human beings, and in so far as they were the genetically unique offspring of their parents – as “children”.</p>
<h2>Two meanings of ‘child’</h2>
<p>But the problem with the ruling (and with an Alabama <a href="https://ballotpedia.org/Alabama_Amendment_2,_State_Abortion_Policy_Amendment_(2018)">constitutional amendment</a> passed in 2018) is the conflation of two ethically distinct meanings of “child”, and hence two different sources of concern.</p>
<p>One sense of a “child” is that of the progeny of parents. Such offspring are (in almost every case) loved and treasured. If a child is harmed or lost it is profoundly distressing to those parents and potentially other family members.</p>
<p>But a second sense of a “child” is of an immature human being, living and growing outside a mother’s body, with a special right to our nurturing, care and protection. If such a child is harmed or dies, there is a significant loss to that child. Even if there were no parents who loved or cared for this child, we should identify this loss as morally significant.</p>
<p>These two different senses of a child can come apart.</p>
<p>The early embryo or foetus is clearly a child in the first sense. Indeed, that is why the parents in the Alabama case have a legitimate claim for damages. However, whether an early embryo or foetus is a “child” in the second sense is deeply contested. </p>
<p>Many philosophers have questioned whether <a href="https://www.jstor.org/stable/24439776">a clump of cells</a> has the same moral status as a six-year-old child or an adult. And indeed most of the wider community, including most religious believers worldwide, share that scepticism. For example, IVF and disposal of unwanted embryos is <a href="https://www.jstor.org/stable/27650544">permitted in Islam</a> because “ensoulment” is not thought to occur until 120 days.</p>
<figure class="align-center ">
<img alt="Human embryo at the very early stages" src="https://images.theconversation.com/files/579190/original/file-20240301-16-jpt089.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/579190/original/file-20240301-16-jpt089.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=479&fit=crop&dpr=1 600w, https://images.theconversation.com/files/579190/original/file-20240301-16-jpt089.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=479&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/579190/original/file-20240301-16-jpt089.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=479&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/579190/original/file-20240301-16-jpt089.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=602&fit=crop&dpr=1 754w, https://images.theconversation.com/files/579190/original/file-20240301-16-jpt089.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=602&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/579190/original/file-20240301-16-jpt089.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=602&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">What is a child?</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/human-cells-egg-208569940">895Studio/Shutterstock</a></span>
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<p>That is why IVF and the use of frozen embryos has been, and continues to be, widely accepted. It is why, in the Alabama case, there were no newspaper headlines at the time, and why there were no calls for criminal prosecution of either the clinic or the wandering patient. It is why the reference to the rights of “unborn children” in conservative laws and rulings is both misleading and mistaken.</p>
<p>There are, of course, different views about when a child (as offspring) becomes a child, with rights and in need of ethical and legal protection. </p>
<p>One problem with laws that refer to “unborn children” is that they simply assume that these two senses of child are the same, when that is open to debate and question. But the other massive problem is that they impose one particular answer to the question, an answer believed by a relatively small number of religious conservatives, on others (religious and non-religious) who do not share that belief. And that is profoundly unjust.</p><img src="https://counter.theconversation.com/content/224818/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Dominic Wilkinson receives funding from the Wellcome Trust. </span></em></p>What constitutes an ‘unborn child’ should not be decided by a relatively small number of religious conservatives.Dominic Wilkinson, Consultant Neonatologist and Professor of Ethics, University of OxfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2107282023-08-13T09:13:34Z2023-08-13T09:13:34ZHow to grow rhinos in a lab: the science that could save an endangered species<figure><img src="https://images.theconversation.com/files/540701/original/file-20230802-27-i9629h.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Najin, one of two northern white rhinos left in the world, grazes in a paddock in Kenya. </span> <span class="attribution"><span class="source">Tony Karumba/AFP via Getty Images</span></span></figcaption></figure><p>There are several parallel projects running across the world to save the northern white rhinoceros (<em>Ceratotherium simum simum</em>), one of Africa’s captivating and iconic wildlife species. With the death of last male in <a href="https://www.bbc.com/news/world-africa-43468066">2018</a> and with only two females alive, the species is functionally extinct.</p>
<p>The most famous of these projects is an international research consortium called <a href="https://biorescue.org/en/home-0">BioRescue</a>. It was founded in 2019 by a team of scientists and conservationists under the leadership of the <a href="https://www.izw-berlin.de/en/mission-vision.html">Leibniz Institute for Zoo & Wildlife Research</a> in Berlin, Germany.</p>
<p>In one of its research lines, the BioRescue team collects mature eggs – scientifically called oocytes – from one of the only two northern white females. They reside in Kenya’s <a href="https://www.olpejetaconservancy.org/">Ol Pejeta Conservancy</a>, a privately run wildlife sanctuary. These eggs will be fertilised with frozen sperm that were collected from several northern white male rhinos before their death. </p>
<p>The two remaining females, Najin and Fatu, are not capable of delivering offspring anymore. Najin’s back legs are too weak to carry a pregnancy and Fatu has problems with her uterus. Therefore, the resulting embryos from the fertilised eggs will be transferred into surrogate mothers. </p>
<p>The most suitable surrogate mother would be a southern white rhino as it is the closest related species. But, placing a northern white rhino embryo in a southern white female rhino isn’t an easy task. However, there was <a href="https://phys.org/news/2023-07-embryos-surrogate-mothers-added-northern.html">promising news</a> in May 2023. Next to the addition of five more northern white embryos – which brings the total to 29 – two wild southern white rhinos were identified as suitable surrogates, as they can still get pregnant and are able to carry the pregnancy through. </p>
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Read more:
<a href="https://theconversation.com/the-case-for-introducing-rhinos-to-australia-99585">The case for introducing rhinos to Australia</a>
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<p>The goal of producing a new northern white rhino calf now seems more realistic than ever before. </p>
<p>Sometimes people <a href="https://theconversation.com/the-northern-white-rhino-should-not-be-brought-back-to-life-94153">question the funding and effort</a> spent on one species, but the science behind the rhinoceros story is much bigger. Any species going extinct has huge consequences on the ecosystem, and people’s survival depends on resources provided by this same ecosystem. As a recognisable, impressive and majestic animal, rhinos certainly have a role as a flagship of conservation efforts. </p>
<p>Further, joint efforts on one species can provide scientific knowledge that allows for a multi-species conservation approach. These techniques would not only save the northern white rhinoceros, but also other rhino species, related species with a common ancestor, and all other creatures in need.</p>
<h2>Different approaches</h2>
<p>Despite the great scientific strides made in efforts to save the northern white rhino, the success rate of embryo transplantation followed by pregnancy to term is <a href="https://raf.bioscientifica.com/view/journals/raf/4/3/RAF-23-0020.xml">extremely low</a>. Parallel initiatives focusing on different conservation approaches are indispensable to ensure the future of this species. </p>
<p>While BioRescue is collecting matured eggs after hormonal stimulation, the <a href="https://www.wrh.ox.ac.uk/research/rhino-fertility-project-1#:%7E:text=Prof%20Suzannah%20Williams%20and%20her,eggs%20in%20a%20laboratory%20setting.">Rhino Fertility Project</a> at the University of Oxford in the UK is focusing on growing follicles, which are structures found in the ovary containing an immature egg surrounded by a few layers of supporting cells. These supporting cells provide signals and components essential for the development of the eggs. The idea is to make use of the much greater potential of the ovary by collecting the very small follicles and growing them all in a petridish in the lab. </p>
<p>This would bypass atresia, which is the degradation of follicles that occurs during a natural hormonal cycle. As member of this project, one of us, Ruth Appeltant, was <a href="https://theconversation.com/only-two-northern-white-rhinos-remain-and-theyre-both-female-heres-how-we-could-make-more-147608">hopeful</a> that this method had the potential to quickly provide a vast number of in vitro-grown oocytes, or mature eggs. </p>
<p>Unfortunately, it became clear that the ovarian tissue of older rhinoceroses contained extremely few to no oocytes. These eggs were needed as the starting material for the project. Without eggs, there is nothing to grow. Ongoing efforts are now looking to establish ways to localise and process the few remaining follicles in old ovarian tissue.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/540161/original/file-20230731-21-xk1xya.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/540161/original/file-20230731-21-xk1xya.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/540161/original/file-20230731-21-xk1xya.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/540161/original/file-20230731-21-xk1xya.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/540161/original/file-20230731-21-xk1xya.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/540161/original/file-20230731-21-xk1xya.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=425&fit=crop&dpr=1 754w, https://images.theconversation.com/files/540161/original/file-20230731-21-xk1xya.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=425&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/540161/original/file-20230731-21-xk1xya.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=425&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">An overview of the focus of different initiatives around the world to save the northern white rhino.</span>
<span class="attribution"><span class="source">Ruth Appeltant</span></span>
</figcaption>
</figure>
<p>This bottleneck led us to the area of <a href="https://blog.uantwerpen.be/fbd/meet-our-researchers-prof-ruth-appeltant/">stem cell technologies</a>. At the <a href="https://www.uantwerpen.be/en/research-groups/veterinary-physiology-biochemistry/research-mission-and-members/research-mission/">Gamete Research Centre</a> of the University of Antwerp in Belgium, our group is aiming to produce eggs outside the body from stem cells. These could be used to conserve endangered species like the rhinoceros.</p>
<p>The BioRescue project and a <a href="https://science.sandiegozoo.org/species/white-rhino">research group at the San Diego Zoo</a> in the US are also aiming to produce artificial eggs from body cells present in tissues. </p>
<p>The common thread is turning cells into <a href="https://www.britannica.com/science/induced-pluripotent-stem-cell">induced pluripotent stem cells</a>, which are immature cells generated from mature cells, and that can in turn differentiate into eggs. In fact, this process can transform a skin cell into an egg. The procedure has so far been <a href="https://www.nature.com/articles/nature20104">completed successfully</a> in mice and could already provide a kind of precursor to oocytes in the northern white rhino. </p>
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Read more:
<a href="https://theconversation.com/even-if-you-were-the-last-rhino-on-earth-why-populations-cant-be-saved-by-a-single-breeding-pair-93733">Even if you were the last rhino on Earth... why populations can't be saved by a single breeding pair</a>
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<p>The collection of oocytes is a really tricky process due to the technical difficulties in reaching the site of the ovaries in living animals. Advanced artificial reproductive techniques using body cells, such as skin cells, introduce a spectrum of new possibilities. Most biological samples stored to date consist of small skin samples, but not of oocytes. </p>
<p>A downside to this approach is the fact that scientists first need to succeed in producing stem cells in the species of interest. </p>
<p>At the University of Antwerp’s <a href="https://www.uantwerpen.be/en/research-groups/veterinary-physiology-biochemistry/research-mission-and-members/research-mission/">Gamete Research Centre</a>, we’re not only interested in developing stem cell technologies based on induced pluripotent stem cells, but are currently establishing the in vitro gametogenesis – or “in vitro oocyte-creation” technique – based on stem cells present in the ovary. Due to a scarcity of tissues from endangered species, we are using the pig as a large animal model. This will give us more in-depth knowledge on how to approach egg creation from stem cells already present in the animal, termed endogenous stem cells. </p>
<h2>What next?</h2>
<p>When we do not have eggs, let’s create them. When we have stem cells, let’s use them. Researchers now know that samples of the northern white rhino individuals currently stored in biobanks have enough genetic variability to establish a viable and sustainable population. </p>
<p>A decade ago, we would have never imagined eggs could be produced from other cells. This is becoming a reality that gives us hope, motivation and energy to save the northern white rhino.</p><img src="https://counter.theconversation.com/content/210728/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ruth Appeltant receives funding from the University of Antwerp.</span></em></p><p class="fine-print"><em><span>Rita L. Sousa receives funding from the University of Antwerp.</span></em></p>Efforts to save one species can provide scientific knowledge that enables us to save other creatures in need.Ruth Appeltant, Assistant research professor, University of AntwerpRita L. Sousa, PhD Candidate, University of AntwerpLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2078572023-06-16T17:34:45Z2023-06-16T17:34:45ZScientists have created embryo models from stem cells – it could help us better understand infertility and miscarriage<figure><img src="https://images.theconversation.com/files/532387/original/file-20230616-19-p8kviv.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C6000%2C3368&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/3d-rendered-illustration-human-embryo-week-2123806805">SciePro/Shutterstock</a></span></figcaption></figure><p>Scientists <a href="https://www.bbc.co.uk/news/health-65914934">recently announced</a> that they have developed embryo models using just stem cells. No sperm or egg cells (oocytes) were involved.</p>
<p>These new research findings were presented by Professor Magdalena Żernicka-Goetz of the University of Cambridge and the California Institute of Technology at the annual meeting of the International Society for Stem Cell Research in Boston. </p>
<p>The work, which is yet to be published in a journal, has prompted a debate about the potential use of embryo models derived from stem cells – known as stem-cell-based embryo models – in research.</p>
<p>So what exactly are these embryo models and how might they advance science?</p>
<p>First, they differ from embryos created by fertilisation, although we don’t yet understand the full extent of the differences from a biological or moral perspective. </p>
<p>Normal embryonic development starts when a sperm fertilises an egg, after which embryos complete a number of cell divisions (cleavage) over about four days. The cells become “squeezed” together in a process called compaction before making a structure called a blastocyst by day five. </p>
<p>The blastocyst is a key stage because it’s around this time that the embryo starts implanting in to the womb – the start of pregnancy. Over the days that follow, the embryo undergoes further development, generating different cells that will ultimately become a fully formed baby.</p>
<p>By about 14 days, the embryo has undergone a process called gastrulation, which forms a structure called the “primitive streak”, setting up the basic pattern of the body.</p>
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Read more:
<a href="https://theconversation.com/scientists-have-created-synthetic-human-embryos-now-we-must-consider-the-ethical-and-moral-quandaries-207911">Scientists have created synthetic human embryos. Now we must consider the ethical and moral quandaries</a>
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<p>By contrast, embryo models are created directly from stem cells – either embryonic stem cells previously isolated from an embryo or pluripotent stem cells (cells that have been reprogrammed under laboratory conditions to become stem cells). </p>
<p>Recent <a href="https://pubmed.ncbi.nlm.nih.gov/29720634/">research</a> from a <a href="https://pubmed.ncbi.nlm.nih.gov/34856602/">number of groups</a> has shown that <a href="https://pubmed.ncbi.nlm.nih.gov/34548496/">stem cells</a> can, under <a href="https://pubmed.ncbi.nlm.nih.gov/35988542/">special laboratory conditions</a>, be persuaded to form a structure that resembles a blastocyst. These structures are what we’ve come to call “stem-cell-based embryo models”.</p>
<p>Żernicka-Goetz described culturing the embryo model to a stage of development just beyond the 14-day stage of gastrulation.</p>
<h2>An exciting prospect for science</h2>
<p>Research with fertilised embryos is a carefully regulated area of science. Notably, research using human embryos must stop no later than the point of <a href="https://www.legislation.gov.uk/ukpga/1990/37/contents">14 days development</a>, before the primitive streak emerges. </p>
<p>This restriction has inevitably limited research into the crucial stage of development when the embryo would implant in to the womb if it was in a body. We know remarkably little about this step in human development. Embryo models could help us understand infertility and early pregnancy loss.</p>
<p>While embryo models are not the same as fertilised embryos, their similarities mean they could be used to study aspects of reproduction that scientists currently can’t investigate.</p>
<p>To realise the potential of these models, we need to discover the similarities – and differences – between embryo models and regular embryos.</p>
<p>For example, the fact that embryo models don’t require eggs or sperm may mean that they are different to fertilised embryos. Also, circumventing the cleavage steps might signify important biological differences between embryo models and fertilised embryos.</p>
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<p>Currently, there is no evidence that these are able to develop in the womb. A <a href="https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00080-2?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1934590923000802%3Fshowall%3Dtrue">recent study</a> in monkeys found that embryo models derived from monkey stem cells were unable to develop beyond a few days in the womb.</p>
<p>We don’t yet know whether this inability to develop is an intrinsic limitation of embryo models or technical limitations that may be overcome by improved understanding and better methods.</p>
<p>But the transfers did elicit a pregnancy-type response in the female animals, indicating the value of embryo models in studying the early stages of implantation.</p>
<h2>Ethics and regulation</h2>
<p>There are robust governance frameworks and laws <a href="https://www.legislation.gov.uk/ukpga/1990/37/contents">in the UK</a> for research with fertilised embryos. However, embryo models don’t fit neatly in to this system because the law was drafted before the technology was developed. They’re not the same as fertilised embryos – and are probably not “embryos” at all under the legislation.</p>
<p>Even though embryo models are not fertilised embryos and don’t have a beating heart or the beginnings of a brain, research must be responsibly conducted and the implications carefully considered. </p>
<p>At an international level, <a href="https://www.isscr.org/guidelines">guidance for research</a> with embryo models has been proposed by the International Society for Stem Cell Research. An important step will be to implement the international guidance at a national level. </p>
<p>In the UK, scientists, lawyers and ethicists are already working on <a href="https://www.cam.ac.uk/research/news/project-launched-to-provide-guidance-on-research-using-human-stem-cell-based-embryo-models">new guidelines</a> on how to work with embryo models, which will hopefully give the public confidence in this work.</p>
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Read more:
<a href="https://theconversation.com/first-working-eggs-made-from-stem-cells-points-to-fertility-breakthrough-67192">First working eggs made from stem cells points to fertility breakthrough</a>
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<p>We have learned from past experience that we need to scan the horizon for potential scientific advances so that we can prepare to introduce them safely and responsibly.</p><img src="https://counter.theconversation.com/content/207857/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Roger Sturmey receives research funding from UKRI, NC3Rs, Tommys, ESHRE, and British Heart Foundation. He serves as Chair of the Guideline Working Group for the "Governing Stem Cell-Based Embryo Models" project led by Cambridge Reproduction. In addition he is Chair of the Scientific Advisory Panel for the UK Association of Reproductive and Clinical Scientists, a committee member of the Association of Embryo technology in Europe, although is not commenting in either capacity. He holds a personal membership of The Labour Party. </span></em></p>These models could help us better understand infertility and early pregnancy loss.Roger Sturmey, Professor of Reproductive Medicine, University of HullLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2079112023-06-16T05:11:13Z2023-06-16T05:11:13ZScientists have created synthetic human embryos. Now we must consider the ethical and moral quandaries<figure><img src="https://images.theconversation.com/files/532335/original/file-20230616-27-q1yird.jpg?ixlib=rb-1.1.0&rect=1%2C0%2C997%2C562&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/embryonic-stem-cell-human-microscope-background-2187993411">Shutterstock</a></span></figcaption></figure><p>Researchers have created synthetic human embryos using stem cells, according to <a href="https://www.bbc.com/news/health-65914934">media</a> <a href="https://www.theguardian.com/science/2023/jun/14/synthetic-human-embryos-created-in-groundbreaking-advance">reports</a>. Remarkably, these embryos have reportedly been created from embryonic stem cells, meaning they do not require sperm and ova.</p>
<p>This development, widely described as a breakthrough that could help scientists learn more about human development and genetic disorders, was revealed this week in Boston at the <a href="https://www.isscr.org/upcoming-programs/isscr-2023">annual meeting</a> of the International Society for Stem Cell Research.</p>
<p>The research, announced by Professor Magdalena Żernicka-Goetz of the University of Cambridge and the California Institute of Technology, has not yet been published in a peer-reviewed journal. But Żernicka-Goetz told the meeting these human-like embryos had been made by reprogramming human embryonic stem cells. </p>
<p>So what does all this mean for science, and what ethical issues does it present?</p>
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Read more:
<a href="https://theconversation.com/worlds-first-synthetic-embryo-why-this-research-is-more-important-than-you-think-188217">World's first 'synthetic embryo': why this research is more important than you think</a>
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<h2>What did the researchers do?</h2>
<p>Each of these synthetic human embryos is created from a single stem cell. Żernicka-Goetz described how her team grew the synthetic embryos to a stage of development called “gastriculation”, which is a stage just beyond the 14-day developmental mark for a human embryo. </p>
<p>The current legal limit to how long a human embryo can be permitted to develop in a lab is 14 days.</p>
<p>This is approximately the length of time from fertilisation of the egg to implantation in the uterine wall, if conception has taken place within a human womb.</p>
<p>So, synthetic embryos have – for the first time – been allowed to develop past this point. </p>
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<p>Initially, the 14-day rule was both a moral and a practical limit; scientists didn’t have the technology to keep embryos alive longer than this. </p>
<p>But the International Society for Stem Cell Research’s 2016 <a href="https://www.sciencealert.com/stem-cell-research-community-drops-14-day-limit-on-human-embryo-research">guidelines</a> also suggested the 14-day limit was morally appropriate, as past this point the cells within the embryo begin to differentiate to form important body systems like the gut, brain and lungs. </p>
<p>The International Society for Stem Cell Research’s updated 2021 <a href="https://www.isscr.org/guidelines/#guidelineskeytopics">guidelines</a> now say we should reconsider the 14-day rule, via public debate, to perhaps allow research on embryos later into development in some cases. </p>
<p>From what has been <a href="https://www.theguardian.com/science/2023/jun/14/synthetic-human-embryos-created-in-groundbreaking-advance">reported</a> about Żernicka-Goetz and her team’s research, the creation of synthetic human-like embryos is a significant advance. </p>
<p>It’s further remarkable they seem to behave, in terms of development, like a human embryo would in some ways. </p>
<p>Żernicka-Goetz reported the human-like embryos began to develop placenta and yolk sacs, but not a beating heart or the beginning of a brain. </p>
<p>Despite the role of the placenta in pregnancy, and its importance to the health of mother and fetus, we know surprisingly little about this vital but temporary <a href="https://www.nichd.nih.gov/research/supported/human-placenta-project/default">organ</a>.</p>
<p>If it was possible to observe placenta in a lab via these synthetic embryos, this could yield valuable knowledge. </p>
<h2>Moral quandaries</h2>
<p>However, just as there are real possibilities for gaining knowledge from synthetic human-like embryos, there are also real moral quandaries.</p>
<p>One of these quandaries arises around whether their creation really gets us away from the use of human embryos. </p>
<p>Robin Lovell-Badge, the head of stem cell biology and developmental genetics at the Francis Crick Institute in London UK, reportedly <a href="https://www.theguardian.com/science/2023/jun/14/synthetic-human-embryos-created-in-groundbreaking-advance">said</a> that if these human-like embryos can really model human development in the early stages of pregnancy, then we will not have to use human embryos for research.</p>
<p>At the moment, it is unclear if this is the case for two reasons.</p>
<p>First, the embryos were created from human embryonic stem cells, so it seems they do still need human embryos for their creation. Perhaps more light will be shed on this when Żernicka-Goetz’s research is published. </p>
<p>Second, there are questions about the extent to which these human-like embryos really can model human development. </p>
<p>At the moment, animal models of similar synthetic embryos suggest they are not capable of developing into a full living being. <a href="https://www.cell.com/cell/fulltext/S0092-8674(22)00981-3?utm_source=STAT+Newsletters&utm_campaign=492bf84a1c-MR_COPY_01&utm_medium=email&utm_term=0_8cab1d7961-492bf84a1c-149563237">Studies</a> in mice and monkeys have so far shown that the synthetic embryos die a short while after being implanted into a female’s womb, which means they are not viable. </p>
<p>There could be significant limits to the usefulness of these synthetic embryos for learning about human developmental issues, if human-like synthetic embryos aren’t capable of developing into full human babies and do not form important body structures like a beating heart and a brain.</p>
<p>One of the reasons researchers want to use these embryos is for research into miscarriage and developmental anomalies. This is very important, but will these synthetic embryos be “close enough” to real human embryos to reveal useful answers?</p>
<p>Scientists may still rely on the use of human embryos if we do need human embryos for the creation of these models, or there are research questions that these synthetic embryos can’t address.</p>
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<h2>Is it morally permissable?</h2>
<p>This leaves us with the important moral question about whether it is permissible to use human embryos for research.</p>
<p>Further, if the human-like synthetic embryos are capable of developing into full living beings, then we must consider whether it is morally permissible to create them just for research. </p>
<p>It could be that they are not currently capable of developing much further than the 14-day mark. </p>
<p>Scientists might decide that this is a problem that needs to be fixed, partly for practical reasons about the limits to their usefulness. Scientists might then fix these synthetic embryos so that they could continue to develop. However, this would create a huge moral quandary. </p>
<p>We should think carefully about whether it is ethical to create living human-like beings only to conduct research on them.</p>
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Read more:
<a href="https://theconversation.com/researchers-have-grown-human-embryos-from-skin-cells-what-does-that-mean-and-is-it-ethical-157228">Researchers have grown 'human embryos' from skin cells. What does that mean, and is it ethical?</a>
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<img src="https://counter.theconversation.com/content/207911/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kathryn MacKay 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 should think carefully about whether it is ethical to create living human-like beings only to conduct research on them.Kathryn MacKay, Senior Lecturer in Bioethics, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2036482023-04-12T17:37:45Z2023-04-12T17:37:45ZCreating and implanting synthetic monkey embryos could pave the way to stem-cell babies<figure><img src="https://images.theconversation.com/files/520569/original/file-20230412-28-ajhtdp.jpg?ixlib=rb-1.1.0&rect=0%2C10%2C7000%2C4977&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Scientists created monkey embryo-like structures and implanted them, although no fetuses formed.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><iframe style="width: 100%; height: 100px; border: none; position: relative; z-index: 1;" allowtransparency="" allow="clipboard-read; clipboard-write" src="https://narrations.ad-auris.com/widget/the-conversation-canada/creating-and-implanting-synthetic-monkey-embryos-could-pave-the-way-to-stem-cell-babies" width="100%" height="400"></iframe>
<p>In January 2017, I met Jiankui He, the now-infamous Chinese scientist who would go on to <a href="https://doi.org/10.1093/jlb/lsz010">create the world’s first genome-edited babies</a>. This was at a meeting in Berkeley, Calif., hosted by Jennifer Doudna who, along with Emmanuelle Charpentier, was awarded the 2020 Nobel Prize in Chemistry for her work on CRISPR genome-editing technology.</p>
<p>At this meeting, geneticist George Church, known for his work to revive the woolly mammoth, described research on “synthetic human embryos” derived from stem cells. Church dubbed these embryo-like structures “<a href="https://doi.org/10.7554/eLife.20674">synthetic human entities with embryo-like features</a>.” </p>
<p>At the time, Church called for <a href="https://doi.org/10.7554/elife.20674">careful sustained dialogue about the moral merits of the 14-day limit on human embryo research</a>.</p>
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<figcaption><span class="caption">George Church’s lecture titled ‘Future, Human, Nature,’ delivered at the Innovative Genomics Institute in January 2017.</span></figcaption>
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<h2>Monkey embryo-like structures</h2>
<p>This month, a team of Chinese scientists created “<a href="https://doi.org/10.1016/j.stem.2023.03.009">synthetic monkey embryos</a>” or, more precisely, synthetic monkey embryo-like structures from stem cells and used these for reproduction. </p>
<p>The reported research involved an <em>in vitro</em> study — meaning it was conducted in the lab — as well as an <em>in vivo</em> study, conducted in the body.</p>
<p>The <em>in vitro</em> study involved the ongoing culture of the monkey embryo-like structures in the lab to see how they might develop after the time at which implantation would typically occur. </p>
<p>Under the microscope, these embryo-like structures initially looked like “natural” early-stage embryos — embryos created using eggs, sperm and fertilization. They became disorganized over time, however, and only five of 484 early-stage synthetic embryos survived to Day 17.</p>
<p>The <em>in vivo</em> study involved the transfer of seven-day-old monkey embryo-like structures to eight female monkeys in the hope of initiating a pregnancy. Implantation occurred in three of the monkeys, but the pregnancies were short-lived. The synthetic monkey embryos stopped developing within 20 days post-transfer and no fetuses formed.</p>
<h2>Initiating pregnancy</h2>
<p>The creation of non-human embryo-like structures is not new. In 2022, two research teams — <a href="https://doi.org/10.1016/j.cell.2022.07.028">one in Israel</a> and <a href="https://doi.org/10.1038/s41586-022-05246-3">another in the United Kingdom</a> — reported on the creation of mouse embryo-like structures from mouse stem cells.</p>
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<span class="caption">A microscopic image of a synthetic mouse embryo with colours added to show brain and heart formation.</span>
<span class="attribution"><span class="source">(Gianluca Amadei, Charlotte Handford via AP)</span></span>
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<p>The attempt to initiate a pregnancy in female monkeys using monkey embryo-like structures is new, however, and suggests that it might one day be possible to attempt the same in humans. Presumably the goal would be to allow scientists to study early human development, including neurodevelopment, and to study pregnancy loss.</p>
<p>This most recent research raises a critical ethical question: Are synthetic human-like embryo structures sufficiently different from human embryos created by fertilization to be exempt from the current limits on human embryo research? </p>
<p>The question is timely as researchers have already <a href="https://doi.org/10.1038/s41586-021-04267-8">used human stem cells</a> to <a href="https://doi.org/10.1038/s41421-021-00316-8">create a human blastocyst model</a>.</p>
<p>Some researchers may argue that “synthetic” and “natural” human embryos are not the same, and that synthetic human embryos should not be subject to the rules governing natural human embryos. Others will disagree. </p>
<p>Presumably the truth of the matter will turn on whether the synthetic embryos can produce a live baby, but the only way to know this is to do the experiment.</p>
<h2>Research guidelines</h2>
<p>Clearly this research, and earlier studies, challenge the current international consensus on the 14-day rule that dictates human embryos cannot be maintained in the laboratory beyond 14 days post-fertilization. The 14-day rule is <a href="https://laws-lois.justice.gc.ca/eng/acts/a-13.4/fulltext.html">the law in Canada</a>, and is a widely accepted research guideline in many countries around the world. It prohibits the development of human embryos outside the human body beyond 14 days.</p>
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Read more:
<a href="https://theconversation.com/stem-cell-research-community-drops-14-day-limit-on-human-embryo-research-161616">Stem cell research community drops 14-day limit on human embryo research</a>
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<p>This limit was introduced in the early 1980s. Up to 14 days, it was possible for one human embryo to split and become twins or for two human embryos to recombine and become a single individual. </p>
<p>On the basis of these biological facts, some reasoned that prior to 14 days, human embryos were not discrete individuals and so they were not protectable human life. They could be used for research in a lab and then discarded. </p>
<p>Others who also supported a 14-day limit on human embryo research focused on a different developmental milestone, <a href="https://doi.org/10.1002/bies.200900038">the primitive streak</a>, which usually appears on Day 15 and signals the development of the nervous system and the brain. </p>
<p>Prior to 14 days, the human embryo could not experience pain and did not have the capacity for human reasoning. On this basis, a similar conclusion was reached: human embryos could be the legitimate subject of research until 14 days.</p>
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<h2>Arbitrary limit?</h2>
<p>For some time now, scientists have argued that <a href="http://dx.doi.org/10.1136/medethics-2020-106406">the 14-day limit is arbitrary and should be changed</a>. Now that it’s possible to maintain natural embryos in culture beyond 14 days, and may be possible to do so as well for synthetic embryos, some members of the scientific community insist that the 14-day limit should be revised or eliminated.</p>
<p>This notion became entrenched in the <a href="https://www.isscr.org/guidelines">2021 research guidelines of the International Society for Stem Cell Research</a>. The 2016 research guidelines prohibited human embryo research beyond 14 days; however, <a href="https://www.technologyreview.com/2021/03/16/1020879/scientists-14-day-limit-stem-cell-human-embryo-research/">the updated guidelines dropped this prohibition</a> and did not propose an alternative — <a href="https://doi.org/10.1038/d41586-021-01697-2">something that colleagues and I have been critical of</a>.</p>
<p>All of this has me wondering if in the not-too-distant future, I (and others) will be commenting on the ethics of the world’s first stem-cell babies. If so, will the commentary be similar to the response to the first genome-edited babies, which was uniformly critical? Or, by that time, will some celebrate this as a creative way to make designer babies?</p><img src="https://counter.theconversation.com/content/203648/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Françoise Baylis is a member of the Governing Board of the International Science Council</span></em></p>In April, scientists implanted synthetic monkey embryos in female monkeys. While none of them developed into fetuses, this is a new development that raises important ethical questions.Françoise Baylis, Distinguished Research Professor, Emerita, Dalhousie UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1905302022-09-14T00:50:43Z2022-09-14T00:50:43ZScientists have mimicked an embryo’s heart to unlock the secrets of how blood cells are born<figure><img src="https://images.theconversation.com/files/484449/original/file-20220913-4701-66g2bb.jpg?ixlib=rb-1.1.0&rect=0%2C1846%2C4019%2C2842&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">UNSW/Jingjing Li</span>, <span class="license">Author provided</span></span></figcaption></figure><p>Stem cells are the starting point for all other cells in our bodies. The <a href="https://www.eurostemcell.org/blood-stem-cells-pioneers-stem-cell-research">first such cells to be found</a> were blood stem cells – as the name suggests, they give rise to different types of blood cells. </p>
<p>But there’s much we don’t know about how these cells develop in the first place. In a study published today in <a href="https://doi.org/10.1016/j.celrep.2022.111339">Cell Reports</a>, we have shown how a lab simulation of an embryo’s beating heart and circulation lead to the development of human blood stem cell precursors.</p>
<p>The tiny device mimics embryonic blood flow, allowing us to directly observe human embryonic blood formation under the microscope. These results may help us understand how we can produce life-saving therapies for patients who need new blood stem cells.</p>
<h2>Growing life-saving therapies in the lab</h2>
<p>To treat aggressive blood cancers such as leukaemia, patients often need extremely high doses of chemotherapy; a <a href="https://www.cancer.nsw.gov.au/myeloma/diagnosis-and-treatment/treatment/types-of-treatment/stem-cell-transplant#:%7E:text=A%20stem%20cell%20transplant%20involves%20killing%20blood%20cells,they%20are%20collected%20beforehand%20and%20kept%20in%20storage.">blood stem cell transplant</a> then regenerates blood after the treatment. These are life-saving therapies but are restricted to patients who have a suitable tissue-matched donor of blood stem cells.</p>
<p>A way around this problem would be to grow more blood stem cells in the lab. Unfortunately, past experiments have shown that harvested adult blood stem cells lose their transplantation potential if grown in the lab. </p>
<p>The discovery of <a href="https://en.wikipedia.org/wiki/Induced_pluripotent_stem_cell">induced pluripotent stem cells</a> – stem cells made out of adult cells – in 2006 led to a promising new approach. Induced pluripotent stem cells are made from the patient’s own cells, so there is no problem with tissue rejection, or the ethical issues surrounding the use of IVF embryos.</p>
<p>These cell lines are similar to embryonic stem cells, so they have the potential to form any tissue or cell type – hence, they are “pluripotent”. In theory, pluripotent stem cell lines could provide an unlimited supply of cells for blood regeneration because <a href="https://en.wikipedia.org/wiki/Immortalised_cell_line">they are immortalised</a> – they can grow in the lab indefinitely.</p>
<p>But the development of processes to allow us to grow particular types of tissues, organs and cell types – such as blood – has been slow and will take decades to advance. One must mimic the complex process of embryogenesis in the dish!</p>
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Read more:
<a href="https://theconversation.com/worlds-first-synthetic-embryo-why-this-research-is-more-important-than-you-think-188217">World's first 'synthetic embryo': why this research is more important than you think</a>
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<h2>Engineering an embryonic heart</h2>
<p>Current understanding of how embryonic blood stem cells develop is based on animal models. Experiments with anaesthetised zebrafish embryos have shown that blood stem cells arise in the wall of <a href="https://pubmed.ncbi.nlm.nih.gov/20154733/">the main blood vessel, the aorta</a>, shortly after the first heartbeat. For ethical reasons, it’s obvious this type of study is not possible in human embryos.</p>
<p>This is why we wanted to engineer an embryonic heart model in the lab. To achieve this, we used <a href="https://www.elveflow.com/microfluidic-reviews/general-microfluidics/a-general-overview-of-microfluidics/">microfluidics</a> – an approach that involves manipulating extremely small volumes of liquids.</p>
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<img alt="A clear chip with colourful tubes coming out on both ends" src="https://images.theconversation.com/files/484242/original/file-20220913-18-2q7zzk.jpg?ixlib=rb-1.1.0&rect=7%2C12%2C698%2C516&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/484242/original/file-20220913-18-2q7zzk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=449&fit=crop&dpr=1 600w, https://images.theconversation.com/files/484242/original/file-20220913-18-2q7zzk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=449&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/484242/original/file-20220913-18-2q7zzk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=449&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/484242/original/file-20220913-18-2q7zzk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=565&fit=crop&dpr=1 754w, https://images.theconversation.com/files/484242/original/file-20220913-18-2q7zzk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=565&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/484242/original/file-20220913-18-2q7zzk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=565&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">The microfluidic device, with cell-seeding channels filled with red food dye; the heart ventricular contraction control channels and circulation valve control channels are filled with blue and green food dye respectively.</span>
<span class="attribution"><span class="source">UNSW/Jingjing Li</span>, <span class="license">Author provided</span></span>
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<p>The first step in generating blood stem cells from pluripotent stem cells is to coax the latter to form the site where blood stem cells start growing. This is known as the AGM region (aorta-gonad-mesonephros) of the embryo.</p>
<p>Our miniature heart pump and circulation (3 by 3 centimetres) mimics the mechanical environment in which blood stem cells form in the human embryo. The device pumps culture media – liquids used to grow cells – around a microfluidic circuit to copy what the embryo heart does.</p>
<h2>A step closer to treatment</h2>
<p>Once we got the cells to form the AGM region by stimulating cells on day two of starting our cell culture, we applied what’s known as pulsatile circulatory flow from day 10 to day 26. Blood precursors entered the artificial circulation from blood vessels lining the microfluidic channels. </p>
<p>Then, we harvested the circulating cells and grew them in culture, showing that they developed into various blood components – white blood cells, red blood cells, platelets, and others. In-depth analysis of gene expression in single cells showed that circulatory flow generated aortic and blood stem precursor cells found in the AGM of human embryos.</p>
<p>This means our study has shown how pulsatile circulatory flow enhances the formation of blood stem cell precursors from pluripotent stem cells. It’s knowledge we can use in the future.</p>
<p>The next step in our research is to scale up the production of blood stem cell precursors, and to test their transplant potential in immune-deficient mice that can accept human transplants. We can do this by using large numbers of pluripotent stem cells grown in bioreactors that also mechanically stimulate blood stem cell formation.</p>
<p>If we can easily produce blood stem cells from pluripotent stem cell lines, it would provide a plentiful supply of these cells to help treatments of cancer or genetic blood diseases.</p>
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Read more:
<a href="https://theconversation.com/gut-bacteria-nurture-the-immune-system-for-cancer-patients-a-diverse-microbiome-can-protect-against-dangerous-treatment-complications-184427">Gut bacteria nurture the immune system – for cancer patients, a diverse microbiome can protect against dangerous treatment complications</a>
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<p class="fine-print"><em><span>This research was funded by Stem Cells Australia (ARC Special Research Initiative in Stem Cell Science) and an internal grant from the Faculty of Engineering, University of New South Wales.</span></em></p><p class="fine-print"><em><span> Jingjing Li received Australia Postgraduate Award (APA) scholarship, Women in Engineering Research Top-Up Award and Engineering Supplementary Award (ESA) from University of New South Wales. </span></em></p>Growing cells we can use to produce blood is key to life-saving therapies after cancer treatment – this device has taken us a step closer.Robert E Nordon, Associate Professor, Biomedical Engineering, UNSW SydneyJingjing Li, Postdoctoral Fellow, Biomedical Engineering, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1879042022-09-01T12:24:52Z2022-09-01T12:24:52ZMost human embryos naturally die after conception – restrictive abortion laws fail to take this embryo loss into account<figure><img src="https://images.theconversation.com/files/482135/original/file-20220831-22-3h2hxf.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1298%2C1029&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The majority of fertilized eggs die and are resorbed into the body.</span> <span class="attribution"><a class="source" href="https://flic.kr/p/JsYKsc">ZEISS Microscopy/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Many state legislatures are seriously considering human embryos at the earliest stages of development for <a href="https://news.bloomberglaw.com/us-law-week/fetal-rights-laws-impact-extends-from-abortion-to-hov-lanes">legal personhood</a>. <a href="https://www.frc.org/blog/2021/07/state-round-total-abortion-bans">Total abortion bans</a> that consider humans to have full rights from the moment of conception have created a <a href="https://www.washingtonpost.com/health/2022/06/28/abortion-ban-roe-doctors-confusion/">confusing legal domain</a> that affects a <a href="https://time.com/6191886/fetal-personhood-laws-roe-abortion/">wide range of areas</a>, including assisted reproductive technologies, contraception, essential medical care and parental rights, among others. </p>
<p>However, an important biological feature of human embryos has been left out of a lot of ethical and even scientific discussion informing reproductive policy – <a href="https://doi.org/10.1007/s10815-020-01749-y">most human embryos die</a> before anyone, including doctors, even know they exist. This embryo loss typically occurs in the first two months after fertilization, before the clump of cells has developed into a <a href="https://bio.libretexts.org/Bookshelves/Human_Biology/Book%3A_Human_Biology_(Wakim_and_Grewal)/23%3A_Human_Growth_and_Development/23.4%3A_Fetal_Stage">fetus</a> with immature forms of the body’s major organs. Total abortion bans that define personhood at conception mean that full legal rights exist for a 5-day-old blastocyst, a hollow ball of cells roughly <a href="https://biologydictionary.net/blastocyst/">0.008 inches (0.2 millimeters)</a> across with a high likelihood of disintegrating within a few days.</p>
<p>As an <a href="https://scholar.google.com/citations?user=ijKRO44AAAAJ&hl=en">evolutionary biologist</a> whose career has focused on how embryos develop in a wide variety of species over the course of evolution, I was struck by the extraordinarily high likelihood that most human embryos die due to random genetic errors. Around <a href="https://doi.org/10.1186/1741-7015-11-154">60% of embryos disintegrate</a> before people may even be aware that they are pregnant. Another 10% of pregnancies end in miscarriage, after the person knows they’re pregnant. These losses make clear that the vast majority of human embryos don’t survive to birth.</p>
<p>The emerging scientific consensus is that high rate of early embryo loss is a common and normal occurrence in people. Research on the causes and evolutionary reasons for early embryo loss provides insight into this fundamental feature of human biology and its implications for reproductive health decisions.</p>
<h2>Intrinsic embryo loss is common in mammals</h2>
<p>Intrinsic embryo loss, or embryo death due to internal factors like genetics, is common in <a href="https://doi.org/10.1007/978-94-009-5038-2_2">many mammals</a>, such as <a href="https://doi.org/10.1095/biolreprod60.6.1273">cows</a> and <a href="https://doi.org/10.2527/1994.72suppl_316x">sheep</a>. This persistent “<a href="https://doi.org/10.1007/978-94-009-5038-2_1">reproductive wastage</a>” has <a href="https://doi.org/10.1093/jas/skaa288">frustrated breeders</a> attempting to increase livestock production but who are unable to eliminate high embryonic mortality. </p>
<p>In contrast, most embryo loss in animals that lay eggs like <a href="https://doi.org/10.1023/A:1011069126615">fish</a> and <a href="http://www.jstor.org/stable/25599224">frogs</a> is due to external factors, such as predators, disease or other environmental threats. These lost embryos are effectively “<a href="https://worldcat.org/en/title/752304487">recycled” in the ecosystem as food</a>. These egg-laying animals have <a href="https://doi.org/10.1016/j.aquaculture.2021.737352">little to</a> <a href="https://doi.org/10.1017/S0266467406003506">no</a> intrinsic embryo loss.</p>
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<figcaption><span class="caption">Each square shows the first 24 hours of embryo development in a different animal species. From left to right: 1. zebrafish (<em>Danio rerio</em>), 2. sea urchin (<em>Lytechinus variegatus</em>), 3. black widow spider (<em>Latrodectus</em>), 4. tardigrade (<em>Hypsibius dujardini</em>), 5. sea squirt (<em>Ciona intestinalis</em>), 6. comb jelly (<em>Ctenophore</em>, <em>Mnemiopsis leidyi</em>), 7. parchment tube worm (<em>Chaetopterus variopedatus</em>), 8. roundworm (<em>Caenorhabditis elegans</em>), and 9. slipper snail (<em>Crepidula fornicata</em>).</span></figcaption>
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<p>In people, the <a href="https://doi.org/10.1007/s10815-020-01749-y">most common outcome</a> of reproduction by far is embryo loss due to random genetic errors. An estimated <a href="https://www.verywellfamily.com/making-sense-of-miscarriage-statistics-2371721">70% to 75%</a> of human conceptions fail to survive to birth. That number includes both embryos that are <a href="https://doi.org/10.1002/uog.21922">reabsorbed into the parent’s body</a> before anyone knows an egg has been fertilized and miscarriages that happen later in the pregnancy.</p>
<h2>An evolutionary drive for embryo loss</h2>
<p>In humans, an evolutionary force called <a href="https://doi.org/10.1371/journal.pbio.3001671">meiotic drive</a> plays a role in early embryo loss. Meiotic drive is a type of competition within the genome of unfertilized eggs, where variations of different genes can manipulate the cell division process to favor their own transmission to the offspring over other variations.</p>
<p><a href="https://doi.org/10.1073/pnas.95.5.2361">Statistical models</a> attempting to explain why most human embryos fail to develop usually start by observing that a massive number of random genetic errors occur in the mother’s eggs even before fertilization.</p>
<p>When sperm fertilize eggs, the resulting embryo’s DNA is packaged into 46 chromosomes – 23 from each parent. This genetic information guides the embryo through the <a href="https://doi.org/10.1016/j.cell.2020.11.003">development process</a> as its cells divide and grow. When <a href="https://doi.org/10.1038/ejhg.2011.272">random mistakes</a> occur during chromosome replication, fertilized eggs can inherit cells with these errors and result in a condition called <a href="https://www.nature.com/scitable/topicpage/chromosomal-abnormalities-aneuploidies-290/">aneuploidy</a>, which essentially means “the wrong number of chromosomes.” With the instructions for development now disorganized due to mixed-up chromosomes, embryos with aneuploidy are <a href="https://www.verywellfamily.com/aneuploidy-definition-2371596">usually doomed</a>.</p>
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<a href="https://images.theconversation.com/files/482144/original/file-20220831-3577-zgrz7f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Microscopy image of four early human embryos" src="https://images.theconversation.com/files/482144/original/file-20220831-3577-zgrz7f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/482144/original/file-20220831-3577-zgrz7f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=477&fit=crop&dpr=1 600w, https://images.theconversation.com/files/482144/original/file-20220831-3577-zgrz7f.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=477&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/482144/original/file-20220831-3577-zgrz7f.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=477&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/482144/original/file-20220831-3577-zgrz7f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=600&fit=crop&dpr=1 754w, https://images.theconversation.com/files/482144/original/file-20220831-3577-zgrz7f.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=600&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/482144/original/file-20220831-3577-zgrz7f.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=600&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">As many as three out of four human embryos naturally die in the development process.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/human-egg-royalty-free-image/509171917">Red Hayabusa/iStock via Getty Images Plus</a></span>
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<p>Because human and other mammal embryos are highly protected from environmental threats – unlike animals that lay eggs outside their bodies – researchers have theorized that these early losses have <a href="https://doi.org/10.1371/journal.pbio.3001671">little effect</a> on the reproductive success of the parent. This may allow humans and other mammals to <a href="https://www.jstor.org/stable/2458433">tolerate meiotic drive</a> over evolutionary time.</p>
<p>Counterintuitively, there may even be benefits to the high rates of genetic errors that result in embryo loss. Early loss of aneuploid embryos can direct maternal resources to <a href="https://doi.org/10.1371/journal.pbio.3001671">healthier single newborns</a> rather than twins or multiples. Also, in the deeper evolutionary history of a species, having a huge pool of genetic variants could occasionally provide a beneficial <a href="https://doi.org/10.1038/s41467-019-13669-2">new adaptation</a> that could aid in human survival in changing environments.</p>
<h2>Spontaneous abortion is natural</h2>
<p>Biological data on human embryos brings new questions to consider for <a href="https://www.guttmacher.org/state-policy/explore/overview-abortion-laws">abortion policies</a>.</p>
<p>Although <a href="https://www.guttmacher.org/state-policy/explore/overview-abortion-laws">required in some states</a>, early embryo loss is typically not documented in the medical record. This is because it occurs before the person knows they are pregnant and often coincides with the next menstrual period. Until relatively recently, researchers were unaware of the extremely high rate of early embryo loss in people, and “conception” was an imagined moment <a href="https://doi.org/10.1017/9781107705647">estimated from last menstruation</a>.</p>
<p>How does naturally built-in, massive early embryo loss affect legal protections for human embryos?</p>
<p>Errors that occur during chromosomal replication are <a href="https://www.nature.com/scitable/topicpage/mitosis-meiosis-and-inheritance-476/">essentially random</a>, which means development can be disrupted in different ways in different embryos. However, while both early embryos and <a href="https://doi.org/10.1056/NEJMoa1201569">late fetuses</a> can become inviable due to genetic errors, early and late abortions are <a href="https://www.guttmacher.org/state-policy/explore/overview-abortion-laws">regulated very differently</a>. Some states still require doctors to wait until the health of the pregnant person is endangered before allowing induced abortion of nonviable fetuses.</p>
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<figcaption><span class="caption">In the wake of anti-abortion laws, doctors have refused to treat patients with miscarriages because it uses the same procedures as abortions.</span></figcaption>
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<p>Since so many pregnancies end naturally in their very earliest days, early embryo loss is exceedingly common, though most people won’t know they’ve experienced it. I believe that new laws ignoring this natural occurrence lead to a slippery slope that can put lives and livelihoods at risk.</p>
<p>Between 1973 and 2005, <a href="https://doi.org/10.1215/03616878-1966324">over 400 women were arrested</a> for miscarriage in the U.S. With the current shift toward restrictive abortion policies, the continued criminalization of pregnancies that don’t result in birth, despite how common they are, is a <a href="https://www.brennancenter.org/our-work/analysis-opinion/miscarriage-justice-danger-laws-criminalizing-pregnancy-outcomes">growing concern</a>.</p>
<p>I believe that acknowledging massive early embryo loss as a normal part of human life is one step forward in helping society make rational decisions about reproductive health policy.</p><img src="https://counter.theconversation.com/content/187904/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kathryn Kavanagh 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>Human embryos are far more likely to die than come to term, an evolutionary trait seen across species. Laws granting personhood at conception ignore built-in embryo loss, with potentially grave consequences.Kathryn Kavanagh, Associate Professor of Biology, UMass DartmouthLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1883822022-08-11T16:21:38Z2022-08-11T16:21:38ZFirst synthetic embryos: the scientific breakthrough raises serious ethical questions<figure><img src="https://images.theconversation.com/files/478093/original/file-20220808-22-vk1y8l.jpg?ixlib=rb-1.1.0&rect=1%2C5%2C958%2C462&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">synthetic mouse</span> <span class="attribution"><span class="source">Weizmann Institute of Sciences</span></span></figcaption></figure><p>Children, even some who are too young for school, know you can’t make a baby without sperm and an egg. But a team of researchers in Israel have called into question the basics of what we teach children about the birds and the bees, and created a mouse embryo using <a href="https://www.cell.com/cell/fulltext/S0092-8674%2822%2900981-3">just stem cells</a>. </p>
<p>It lived for eight days, about half a mouse’s gestation period, inside a bioreactor in the lab. </p>
<p><a href="https://pubmed.ncbi.nlm.nih.gov/33731940/">In 2021</a> the research team used the same artificial womb to grow natural mouse embryos (fertilised from sperm and eggs), which lived for 11 days. The lab-created womb, or external uterus, was a breakthrough in itself as embryos could not survive in petri dishes. </p>
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Read more:
<a href="https://theconversation.com/worlds-first-synthetic-embryo-why-this-research-is-more-important-than-you-think-188217">World's first 'synthetic embryo': why this research is more important than you think</a>
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<p>If you’re picturing a kind of silicone womb, think again. The external uterus is a rotating device filled with glass bottles of nutrients. This movement simulates how blood and nutrients flow to the placenta. The device also replicates the atmospheric pressure of a mouse uterus. </p>
<p>Some of the cells were treated with chemicals, which switched on genetic programmes to develop into placenta or yolk sac. Others developed into organs and other tissues without intervention. While most of the stem cells failed, about 0.5% were very similar to a natural eight-day-old embryo with a beating heart, basic nervous system and a yolk-sac. </p>
<p>These new technologies raise several <a href="https://academic.oup.com/medlaw/article/28/2/342/5680368">ethical and legal concerns</a>.</p>
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<h2>Artificial wombs</h2>
<p>In the latest study, the scientists started with collections of stem cells. The conditions created by the external uterus triggered the developmental process that makes a fetus. Although the scientists said we are a long way off synthetic human embryos, the experiment brings us closer to a future where some humans gestate their babies artificially. </p>
<p>Each year <a href="https://www.theguardian.com/global-development/2018/sep/24/why-do-women-still-die-giving-birth#:%7E:text=According%20to%20the%20latest%20UN,roughly%20one%20every%20two%20minutes.">over 300,000 women worldwide die in childbirth</a> or as a result of pregnancy complications, many because they lack basic care. Even in wealthy countries, pregnancy and childbirth is risky and healthcare providers are criticised for <a href="https://www.independent.co.uk/news/health/maternity-failings-negligence-costs-b2129390.html">failing mothers</a>. </p>
<p>There is an urgent need to make healthcare more accessible across the planet, provide better mental health support for mothers and make pregnancy and childbirth safer. In an ideal world every parent should expect excellent care in all aspects of motherhood. This technology could help <a href="https://www.sciencedaily.com/releases/2017/08/170817141714.htm">treat premature babies</a> and give at least some women a different option: a choice of whether to carry their child or use an external uterus. </p>
<p>Some philosophers say <a href="https://www.cambridge.org/core/journals/cambridge-quarterly-of-healthcare-ethics/article/moral-imperative-for-ectogenesis/B88576CE3AF545DF15E977212B709D5B">there is a moral imperative to develop artificial wombs</a> to help remedy the unfairness of parenting roles. But other researchers say artificial wombs would <a href="https://onlinelibrary.wiley.com/doi/10.1111/bioe.12331">threaten a women’s legal right</a> to terminate a pregnancy. </p>
<h2>Synthetic embryos and organs</h2>
<p>In the last few years, scientists have learned more about how to coax stem cells to develop into increasingly sophisticated structures, including ones that mimic the structure and function of human organs (<a href="https://www.nature.com/articles/nmeth.4576.pdf?origin=ppub">organoids</a>). Artificial human <a href="https://www.sciencedaily.com/releases/2022/02/220201074530.htm">kidneys</a>, <a href="https://www.newscientist.com/article/mg25533962-300-what-lab-grown-mini-brains-are-revealing-about-this-mysterious-organ/">brains</a>, <a href="https://www.cell.com/cell/fulltext/S0092-8674(21)00537-7">hearts</a> and more have all been created in a lab, though they are still too rudimentary for medical use. </p>
<p>The issue of whether there are moral differences between using stem cells to produce models of human organs for research and using stem cells to create a synthetic embryo are already <a href="https://www.nature.com/articles/480291b">playing out</a> in law courts.</p>
<p>One of the key differences between organoids and synthetic embryos is their potential. If a synthetic embryo can develop into a living creature, it should have more protection than those which don’t. </p>
<p>Synthetic embryos do not currently have potential to actually create a living mouse. If scientists did make human synthetic embryos, but without the potential to form a living being, they should arguably be treated similarly to organoids. </p>
<p>Some countries (for example <a href="https://www.nhmrc.gov.au/about-us/news-centre/nhmrc-statement-iblastoids">Australia</a>) have taken the position that synthetic embryos such as “blastoids” (which resemble five-to-six-day-old embryos) should be treated like natural embryos, because of similarities in structure. Other countries (such as the <a href="https://www.progress.org.uk/scientists-call-for-new-ethical-guidelines-for-synthetic-embryos/">UK</a>, the <a href="https://www.nature.com/articles/d41586-020-00127-z">US</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8610011/">Japan</a>) treat synthetic embryos as different from embryos because they can’t currently produce a live baby. </p>
<p>Another important legal issue is the source of stem cells and <a href="https://theconversation.com/worlds-first-synthetic-embryo-why-this-research-is-more-important-than-you-think-188217">consent</a>. The synthetic mouse embryo creators used stem cells from early embryos. </p>
<p>However, in the future it might be possible to make synthetic embryos from <a href="https://stemcell.ucla.edu/induced-pluripotent-stem-cells">induced pluripotent stem cells</a> (IPS). The worst case scenario would be a person donates a skin cell to research into producing organs to cure disease but this is used without their knowledge or consent to produce synthetic embryos.</p>
<h2>Cloning</h2>
<p>IPS cells are created by taking a mature cell (such as a skin cell) from a living or dead person and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3584308/">applying treatments </a> which drive it backwards to a more immature state. If the cell could be driven all the way back to an embryonic stem cell, it may one day be possible to use IPS cells to make viable embryos. </p>
<p>That embryo would be a clone of the cell donor. <a href="https://www.pewresearch.org/fact-tank/2017/02/22/20-years-after-dolly-the-sheeps-debut-americans-remain-skeptical-of-cloning/">The public</a> and <a href="https://www.sciencedirect.com/science/article/pii/S0960982203007255">scientists </a> have huge concerns about human cloning. </p>
<p>But it has been possible to clone a human being using a different process called nuclear transfer, for 25 years. Nuclear transfer created <a href="https://dolly.roslin.ed.ac.uk/facts/the-life-of-dolly/index.html">Dolly the Sheep</a> in 1997 and <a href="https://www.nature.com/articles/d41586-019-00292-w">a monkey</a> in 2018. In the late 90s and early 2000s, a flurry of laws introduced <a href="https://archive.nytimes.com/www.nytimes.com/imagepages/2007/11/19/science/20071120_TIER_GRAPHIC.html?action=click&module=RelatedCoverage&pgtype=Article&region=Footer">around the world successfully banned human cloning</a>. </p>
<p>We should not let our fears about cloning stand in the way of crucial research. The benefits could make <a href="https://www.timesofisrael.com/from-just-skin-cells-israeli-lab-makes-synthetic-mouse-embryos-with-beating-hearts/">organ donor waiting lists</a> a thing of the past, save premature babies and give women an option to have children a different way. Cloning, or any other unethical use of the technology, can be prevented by regulation.</p><img src="https://counter.theconversation.com/content/188382/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Julian Savulescu is a a Bioethics Committee consultant for Bayer. He is a Partner Investigator on an Australian Research Council Linkage award (LP190100841, Oct 2020-2023) which involves industry partnership from Illumina. He does not personally receive any funds from Illumina. He receives funding from the Uehiro Foundation on Ethics and Education and the Wellcome Trust. Via his affiliation with the Murdoch Children's Research Institute he received funding from the Victorian State Government via the Operational Infrastructure Support Program. He also receives funding from the Medical Research Future Fund
</span></em></p><p class="fine-print"><em><span>Christopher Gyngell via his affiliation with the Murdoch Children's Research Institute received funding from the Victorian State Government via the Operational Infrastructure Support Program. He also receives funding from the Medical Research Future Fund.</span></em></p><p class="fine-print"><em><span>Tsutomu Sawai receives funding from the AMED Grant Number JP21wm0425021, the JSPS KAKENHI Grant 21K12908, and the Mitsubishi Foundation. He is an Associate Investigator of the Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University.</span></em></p>Adults today may have grown up dreaming they would live to see working jet packs and robot assistants but few people imagined it would be possible to create life without reproductive cells.Julian Savulescu, Visiting Professor in Biomedical Ethics, Murdoch Children's Research Institute; Distinguished Visiting Professor in Law, University of Melbourne; Uehiro Chair in Practical Ethics, University of OxfordChristopher Gyngell, Research Fellow in Biomedical Ethics, The University of MelbourneTsutomu Sawai, Associate Professor, Graduate School of Humanities and Social Sciences, Hiroshima UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1882932022-08-11T04:02:22Z2022-08-11T04:02:22ZSurprise discovery shows you may inherit more from your mum than you think<figure><img src="https://images.theconversation.com/files/478492/original/file-20220810-667-mqu3i1.jpg?ixlib=rb-1.1.0&rect=2%2C0%2C1914%2C1276&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://unsplash.com/photos/QQqXgcPyYec">leah hetteberg/unsplash</a></span></figcaption></figure><p>What if we could inherit more than our parents’ genes? What if we could inherit the ability to turn genes on and off?</p>
<p>These possibilities have come to light after our <a href="https://www.nature.com/articles/s41467-022-32057-x">recent study</a>, published in Nature Communications. We found information in addition to our genes was passed down from mum to offspring to affect how their skeleton develops. That’s the “epigenetic” information that’s normally reset between generations. </p>
<p>Our research was in mice, the first case of its kind in mammals where a long-lasting epigenetic effect from the mother’s egg is carried down to the next generation. This has lifelong consequences for that generation’s health.</p>
<p>However, we cannot be certain the equivalent epigenetic changes are also inherited in humans, including the implications for how our skeleton develops and potential impact on diseases.</p>
<h2>Hold up, what’s epigenetics again?</h2>
<p>Our genes (packages of DNA) tell our body to make certain proteins. But our cells also need instructions to know whether a gene should be used (switched on) or not (switched off). </p>
<p>These instructions come in the form of chemical or “epigenetic” tags (small molecules) that sit on top of the DNA. You accumulate these tags throughout your life.</p>
<p>Think of how punctuation marks help a reader understand a sentence. Epigenetic tags allow the cell to understand a DNA sequence.</p>
<p>Without these epigenetic tags, the cell might make a protein at the wrong time or not at all.</p>
<p>Timing is crucial in how embryos develop. If certain genes are expressed (switched on to produce a protein) too early or too late, an embryo will not develop properly.</p>
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<figcaption><span class="caption">What is epigenetics?</span></figcaption>
</figure>
<h2>What did we find?</h2>
<p>We were interested in understanding the function of a protein in mouse eggs (ova) called SMCHD1. </p>
<p>By removing SMCHD1 from mouse eggs, we found mice that developed from eggs lacking SMCHD1 had an altered skeleton, with some vertebrae in the spine being disrupted.</p>
<p>This could only be explained by an epigenetic change due to the loss of SMCHD1 in the egg.</p>
<p>In particular, we looked at a set of genes known as <em>Hox</em> genes. These encode a series of proteins known to control how mammals’ skeletons develop. </p>
<p><em>Hox</em> genes are found in all animals, from flies to humans, and are crucial for setting up our spine. Evolution has finely tuned the timing of the expression of <em>Hox</em> genes during embryonic development to ensure the skeleton is assembled correctly.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1551709619361239040"}"></div></p>
<p>Our study showed that epigenetic tags established by the mother’s SMCHD1 in her egg can impact how these <em>Hox</em> genes are expressed in her offspring. </p>
<p>The findings are a big surprise because almost all epigenetic tags in the egg are erased shortly after conception. Think of this a bit like a factory reset.</p>
<p>This means it’s unusual to have epigenetic information from the mother’s egg carried on to her offspring to shape how they grow.</p>
<h2>What does this mean for us?</h2>
<p>Our findings suggest even the genes you don’t inherit from your mother can still influence your development.</p>
<p>This may have implications for the children of women with variants in their SMCHD1 gene. Variations in SMCHD1 cause human diseases such as a form of <a href="https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/muscular-dystrophy">muscular dystrophy</a>.</p>
<p>In the future, SMCHD1 might be a target for new medicines to alter how the protein functions and help patients with diseases caused by variations in SMCHD1. So it’s important to understand what consequences the disruption of SMCHD1 in the egg might have on future generations.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/kids-learning-and-health-is-shaped-by-genes-they-dont-inherit-as-well-as-genes-they-do-90852">Kids' learning and health is shaped by genes they don't inherit, as well as genes they do</a>
</strong>
</em>
</p>
<hr>
<h2>How about other diseases?</h2>
<p>Scientists are now beginning to understand that the epigenetic tags added to our genes are sensitive to changes in the environment. This can mean
environmental variations, such as our diet or level of physical activity, can affect how our genes are expressed. However, these changes do not alter the DNA itself. </p>
<p>The epigenetic state undergoes the most changes when the egg is developing and during very early embryonic development, due to the “factory reset” between generations. This means the embryo is more vulnerable to epigenetic, including environmental, changes during this developmental window. </p>
<p>As we discover more cases where epigenetic information is inherited from the mother, there may be instances where the diet or other environmental changes the mother experiences could impact the next generation.</p>
<p>Given that scientists can now study what happens in a single egg, we are well placed to determine how that might happen and work out what exactly we could be inheriting.</p><img src="https://counter.theconversation.com/content/188293/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Marnie Blewitt receives funding from The National Health and Medical Research Council of Australia and has previously received funding from the Bellberry-Viertel Senior Medical Research Fellowship. </span></em></p><p class="fine-print"><em><span>Natalia Benetti receives funding from an Australian Government Research Training Program Scholarship. </span></em></p>Our study in mice shows epigenetic changes in the mother can be passed to her offspring to influence a critical time in how the spine develops.Marnie Blewitt, Head, Molecular Medicine Laboratory, Walter and Eliza Hall InstituteNatalia Benetti, PhD Student, Epigenetics and Development Division, Walter and Eliza Hall InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1637922021-08-23T18:37:26Z2021-08-23T18:37:26ZThe fertility industry is poorly regulated – and would-be parents can lose out on having children as a result<figure><img src="https://images.theconversation.com/files/416106/original/file-20210813-22-wv89iu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Louise Brown, who was the world's first baby to be born from in vitro fertilization (IVF) in 1978, poses with equipment used in early IVF treatments.
</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/louise-brown-who-in-1978-became-the-worlds-first-baby-to-be-news-photo/1004176610?adppopup=true"> Daniel Leal-Olivas/ Getty</a></span></figcaption></figure><p>When embryologist <a href="https://www.courthousenews.com/lab-workers-were-devastated-by-tank-failure-that-destroyed-human-embryos/">Joseph Conaghan arrived at work</a> at San Francisco’s Pacific Fertility Center on March 4, 2018, nothing seemed awry. He did routine inspections of the facility’s cryogenic tanks, which store frozen embryos and eggs for clients who hope to someday have biological children. </p>
<p>But what he found was not routine; it was an emergency. Almost all of the liquid nitrogen inside Tank 4 had drained out. Conaghan and his staff tried to save 80 metal boxes of frozen reproductive material, but it was too late. The contents had warmed, damaging or destroying 1,500 eggs and 2,500 embryos. </p>
<p>Some belonged to a couple who traveled cross-country from their farm in Ohio, hoping to build their family from frozen embryos. A single woman in her early 40s was hoping to soon use her preserved eggs with “Mr. Right.”</p>
<p>For many, infertility is a significant challenge: In 2018, 12.7% of American women sought infertility services, according to a <a href="https://www.cdc.gov/nchs/nsfg/key_statistics/i_2015-2017.htm#infertilityservices">U.S. Centers for Disease Control and Prevention report</a>. As experts on regulation of the fertility industry, we are concerned about protecting those who need these interventions. There is little oversight in the U.S. of the industry, with <a href="https://www.fertstertreports.org/action/showPdf?pii=S2666-3341%2820%2930039-8">no requirement</a> that clinics report problems – including tank failures. As Professor Dov Fox of the University of San Diego Law School told a reporter: “<a href="https://www.washingtonpost.com/health/2021/06/11/fertility-clinic-egg-embryo-verdict/">These tanks specifically, they’re not regulated any better than kitchen appliances or farm tools</a>.”</p>
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<figcaption><span class="caption">The science behind making a baby in a lab.</span></figcaption>
</figure>
<h2>Reproductive innovations</h2>
<p>The current age of reproductive technology dates to 1944, when lab technician <a href="https://www.bbc.com/future/article/20200103-the-female-scientist-who-changed-human-fertility-forever">Miriam Menkin</a> successfully fertilized a human egg in a petri dish. She made history, creating a new method of human conception.</p>
<p>That year, 30 fertility experts founded the <a href="https://www.asrm.org/about-us/history-of-asrm/">American Society for Reproductive Medicine</a>. Today it is a global organization of <a href="https://www.asrm.org/news-and-publications/news-and-research/announcements/asrm-task-force-on-diversity-equity-and-inclusion-issues-statement-recommendations/">about 8,000</a>, including doctors, nurses, health care professionals and others.</p>
<p>But it wasn’t until 1978 that in vitro fertilization emerged as a groundbreaking and controversial technology. That year marked the birth of <a href="https://time.com/5344145/louise-brown-test-tube-baby/">Louise Brown</a>, the first “test tube baby.”</p>
<p>Since then, the procedure has produced more than <a href="https://www.sciencedaily.com/releases/2018/07/180703084127.htm">8 million children</a> worldwide. Some <a href="https://www.cdc.gov/art/artdata/index.html">80,000 children</a> are born yearly in the U.S. through IVF, accounting for <a href="https://www.cdc.gov/art/artdata/index.html">1.9% of births.</a></p>
<h2>Little regulation</h2>
<p>Assisted reproduction is now a multibillion-dollar industry, with more than <a href="https://www.cdc.gov/art/nass/index.html">440 U.S. clinics</a>. In other industrialized nations, including the U.K., fertility treatment is <a href="https://www.hfea.gov.uk/about-us/">monitored</a> by independent, comprehensive regulators. In the U.S., government regulation is so light that the U.S. fertility industry has been called the “<a href="https://www.nytimes.com/roomfordebate/2011/09/13/making-laws-about-making-babies/fertility-industry-is-a-wild-west">Wild West</a>.” U.S. lawmakers have largely steered clear: The contentious battle over abortion has created a political minefield around any issue concerning conception or embryos.</p>
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<p>Minimal <a href="https://www.asrm.org/globalassets/asrm/asrm-content/about-us/pdfs/oversiteofart.pdf">regulations</a> are scattered among <a href="https://www.today.com/health/lack-oversight-regulations-may-lead-ivf-mishaps-t157872">federal, state and professional entities</a>. Meanwhile, the U.S. Centers for Disease Control and Prevention offers limited oversight, <a href="https://www.cdc.gov/art/nass/index.html">auditing or inspecting</a> only a sample of clinics each year, mostly to validate data. </p>
<p>Under a 1992 <a href="https://www.govinfo.gov/content/pkg/STATUTE-106/pdf/STATUTE-106-Pg3146.pdf">U.S. federal law</a>, clinics must <a href="https://www.cdc.gov/art/nass/index.html">report assisted reproduction success rates</a> to the CDC. Labs can be <a href="https://www.pewtrusts.org/en/research-and-analysis/blogs/stateline/2015/3/18/states-not-eager-to-regulate-fertility-industry">certified</a> by <a href="https://www.cap.org/laboratory-improvement/accreditation/reproductive-accreditation-program">one</a> of <a href="https://www.jointcommission.org">two</a> <a href="https://www.cdc.gov/art/nass/policy.html">accrediting, nonprofit organizations</a>. While some states <a href="https://www.washingtonpost.com/news/to-your-health/wp/2018/03/14/faq-are-my-frozen-embryos-safe-everything-you-need-to-know-given-two-fertility-clinics-recent-problems/">require fertility labs to be accredited,</a> others do not; certification <a href="https://www.asrm.org/globalassets/asrm/asrm-content/news-and-publications/practice-guidelines/for-non-members/cryostorage_of_reproductive_tissues.pdf">requires the monitoring of tanks</a>.</p>
<p>Without comprehensive monitoring, there is little known about problems within this industry. Some of the most complete information on frozen embryo mishaps comes from a <a href="https://www.google.com/url?sa=D&q=https://www.fertstertreports.org/action/showPdf%3Fpii%3DS2666-3341%252820%252930039-8&ust=1627324440000000&usg=AOvVaw3blyWRCntiDd2el33sY9SB&hl=en&source=gmail">study</a> analyzing lawsuits from 2009 through 2019. </p>
<p>The authors reported 133 cases of embryo loss. More than half were related to two catastrophic freezer failures, including the San Francisco event and another that occurred, in a bizarre coincidence, on the same day at Ohio’s <a href="https://www.cleveland.com/news/2019/09/uh-freezer-malfunction-update-more-than-150-families-settle-lawsuits-in-loss-of-embryos.html">Ahuja Medical Center</a>. The Ohio malfunction thawed 4,000 eggs, affecting more than 900 women or families.</p>
<p>But this study only includes cases that can be tracked because of legal filings. Clinics often require patients to sign arbitration agreements that keep cases out of court and out of the public eye. </p>
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<h2>The Pacific Fertility Center case</h2>
<p>Cryogenic tank failures should never happen. Although they store often irreplaceable genetic material, this equipment is minimally regulated. </p>
<p>The <a href="https://www.ecfr.gov/cgi-bin/text-idx?SID=13f55385af12d02f3c7cf85f833911fb&mc=true&node=se21.8.884_16120&rgn=div8">U.S. Food and Drug Administration</a> categorizes these tanks as Class II devices and exempts them from <a href="https://www.fda.gov/medical-devices/premarket-submissions/premarket-notification-510k">premarket</a> scientific and regulatory <a href="https://www.fda.gov/medical-devices/premarket-submissions/premarket-approval-pma">review</a> on safety and effectiveness. </p>
<p>There is also little oversight on the equipment while it’s in use. The American Society for Reproductive Medicine issued <a href="https://www.asrm.org/globalassets/asrm/asrm-content/news-and-publications/practice-guidelines/for-non-members/cryostorage_of_reproductive_tissues.pdf">guidance</a> on best practices for cryopreservation in 2020, noting that a “known” source of potential mishaps included “human errors,” such as a “lack of quality control including liquid nitrogen filling schedule” and “inadequate inventory records.”</p>
<p>Basic federal standards for the manufacturing and use of cryopreservation tanks would prevent future storage tank failures and the loss of frozen eggs and embryos. In lieu of federal action, New Jersey became the <a href="https://abovethelaw.com/2020/03/new-jersey-is-the-first-state-to-regulate-the-storage-of-human-embryos/">first state</a> to regulate embryo storage through a law enacted in December 2019. </p>
<p>But ultimately, we believe only federal regulations can ensure uniformity so that standards don’t vary from state to state. Clinics also need greater government oversight to ensure prompt communication about errors. </p>
<p>Many who hope to someday have a genetically related child — like the couple from Ohio and that single woman looking for the right partner — must place their trust in fertility specialists, clinics and equipment manufacturers that provide needed services and devices. Even minimal regulation would help ensure that others are spared from devastating losses in the future. </p>
<p>[<em>Get our best science, health and technology stories.</em> <a href="https://theconversation.com/us/newsletters/science-editors-picks-71/?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=science-best">Sign up for The Conversation’s science newsletter</a>.]</p><img src="https://counter.theconversation.com/content/163792/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Dena Sharp's law firm, Girard Sharp, worked on the cases relating to the tank failure at Pacific Fertility that are discussed in this article. </span></em></p><p class="fine-print"><em><span>Naomi Cahn 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>An unknown number of people have lost their dreams of parenthood because of storage disasters at fertility clinics. These experts note poor government oversight and the need for stronger regulation.Naomi Cahn, Professor of Law, University of VirginiaDena Sharp, Guest lecturer, University of California College of the Law, San FranciscoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1616162021-05-27T16:00:53Z2021-05-27T16:00:53ZStem cell research community drops 14-day limit on human embryo research<figure><img src="https://images.theconversation.com/files/403003/original/file-20210526-17-rsjl91.jpg?ixlib=rb-1.1.0&rect=0%2C16%2C3600%2C2376&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Human embryo research is used to understand foetal development and its applications in treating or eliminating disease.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>The International Society for Stem Cell Research (ISSCR), which bills itself as “<a href="https://www.isscr.org/about-isscr">the voice of the stem cell research community</a>,” has announced that it no longer endorses the prevailing international standard limiting human embryo research to 14 days after fertilization. </p>
<p>Human embryo research has long been a thorny ethical issue because of <a href="https://scholarsarchive.library.albany.edu/cgi/viewcontent.cgi?article=1001&context=cas_philosophy_scholar">competing views about the moral status of the developing embryo</a>. Some people argue that human embryos have the moral status of persons and are considered protectable human life — that embryos should not be used for research, especially research that results in their destruction. </p>
<p>Other people reject such claims, highlighting the potential scientific and therapeutic benefits of research involving human embryos. These benefits include investigation of human development, cancer cell growth, congenital diseases and the causes of miscarriages. Applications of this research include <a href="https://doi.org/10.1002/9781444367072.wbiee691">developing contraceptives, diagnosing genetic diseases, treating infertility and other maladies</a>.</p>
<p>The earlier <a href="https://www.isscr.org/docs/default-source/all-isscr-guidelines/guidelines-2016/isscr-guidelines-for-stem-cell-research-and-clinical-translationd67119731dff6ddbb37cff0000940c19.pdf">ISSCR guidelines from 2016</a> prohibit the cultivation and use of embryos beyond 14 days.</p>
<p>The <a href="https://www.isscr.org/policy/guidelines-for-stem-cell-research-and-clinical-translation">updated guidelines</a> announced May 26 eliminate this prohibition. Instead, the ISSCR recommends that “national academies of science, academic societies, funders and regulators” engage the public in conversation about the scientific, societal and ethical issues associated with the 14-day limit, and whether this should be extended depending on the research objectives.</p>
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<p><a href="https://theconversation.com/growing-human-embryos-in-the-lab-and-why-scientists-just-tweaked-the-rules-podcast-161611"><img src="https://images.theconversation.com/files/403160/original/file-20210527-15-1crjmoe.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=212&fit=crop&dpr=1" alt="Promotional image for podcast" width="100%"></a>
<br></p>
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<h2>A history of the 14-day rule</h2>
<p>The 14-day rule, also known as the 14-day limit, “<a href="https://www.nature.com/news/embryology-policy-revisit-the-14-day-rule-1.19838">became a standard part of embryo-research oversight through the convergence of deliberations of various national committees over decades</a>.”</p>
<p>Today, different countries have different rules more or less closely aligned with one of the competing perspectives on the moral status of human embryos. Some countries — such as <a href="https://www.ris.bka.gv.at/GeltendeFassung.wxe?Abfrage=Bundesnormen&Gesetzesnummer=10003046">Austria</a>, <a href="https://www.gesetze-im-internet.de/eschg/">Germany</a>, <a href="https://www.camera.it/parlam/leggi/04040l.htm">Italy</a>, <a href="http://www.gratanet.com/up_files/biomedical_cell_products_russia_june2016_eng.pdf">Russia</a> and <a href="https://www.mevzuat.gov.tr/mevzuat?MevzuatNo=20085&MevzuatTur=7&MevzuatTertip=5">Turkey</a> — do not permit research involving human embryos. </p>
<p>Other countries — including <a href="https://www.laws-lois.justice.gc.ca/eng/acts/A-13.4/FullText.html">Canada</a>, <a href="https://drive.google.com/file/d/1hYFmm2rRnhRdvxPiWR5vQh7Y5I9BCwxk/view">China</a>, <a href="http://dbtindia.gov.in/sites/default/files/National_Guidelines_StemCellResearch-2017.pdf">India</a>, <a href="https://www.lifescience.mext.go.jp/files/pdf/n743_00.pdf">Japan</a>, <a href="https://www.boe.es/buscar/pdf/2007/BOE-A-2007-12945-consolidado.pdf">Spain</a> and the <a href="https://www.legislation.gov.uk/ukpga/1990/37/contents">United Kingdom</a> — permit limited human embryo research up to (and not beyond) 14 days. Still other countries permit such research without stipulating any kind of time limit, for example, <a href="http://www.planalto.gov.br/ccivil_03/_Ato2004-2006/2005/Lei/L11105.htm">Brazil</a> and <a href="https://www.legifrance.gouv.fr/codes/id/LEGISCTA000006171138/">France</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/403005/original/file-20210526-15-o38mcc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="An illustration of a foetus floating in a bubble on a blue background" src="https://images.theconversation.com/files/403005/original/file-20210526-15-o38mcc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/403005/original/file-20210526-15-o38mcc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/403005/original/file-20210526-15-o38mcc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/403005/original/file-20210526-15-o38mcc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/403005/original/file-20210526-15-o38mcc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/403005/original/file-20210526-15-o38mcc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/403005/original/file-20210526-15-o38mcc.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">A 3D illustration of a one-month-old fetus. The primitive streak is the precursor to the spinal cord.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>In 1979, following extensive public consultation, the Ethics Advisory Board of the United States Department of Health, Education and Welfare issued a report in support of limited human embryo research. The board concluded that research involving human embryos should be allowed, provided the embryos were not “<a href="https://repository.library.georgetown.edu/bitstream/handle/10822/559350/HEW_IVF_report.pdf">sustained in vitro beyond the stage normally associated with the completion of implantation (14 days after fertilization)</a>.”</p>
<p>Five years later, also following extensive public consultation, the <a href="https://www.hfea.gov.uk/media/2608/warnock-report-of-the-committee-of-inquiry-into-human-fertilisation-and-embryology-1984.pdf">Warnock Report of the Committee of Inquiry into Human Fertilisation and Embryology</a> in the U.K. reached a similar conclusion. The emphasis in this report, however, was on a different biological phenomenon: the appearance of the primitive streak (a precursor to the brain and spinal cord), which appears on the 14th or 15th day after fertilization.</p>
<p>The first national law entrenching the proposed ethical limit of 14 days was introduced in the U.K. in the <a href="https://www.legislation.gov.uk/ukpga/1990/37/contents">Human Fertilisation and Embryology Act of 1990</a>. Since then other countries (but not the U.S.) have followed suit and introduced similar legislation. </p>
<p>In Canada, the <a href="https://laws-lois.justice.gc.ca/eng/acts/a-13.4/fulltext.html">Assisted Human Reproduction Act of 2004</a> stipulates that no person shall knowingly “maintain an embryo outside the body of a female person after the 14th day of its development following fertilization or creation, excluding any time during which its development has been suspended.”</p>
<p>Until now, the ISSCR guidelines have been in lockstep with laws, regulations and guidelines endorsing the 14-day limit. No more.</p>
<h2>Merits of the prohibition</h2>
<p>The decision to jettison the established 14-day rule is a mistake. <a href="https://dx.doi.org/10.1002/hast.1215">There is good reason</a> to recommend public discussion and debate on the merits of this rule. There is no legitimate reason, however, for this discussion to focus narrowly on extending the research time limit. For example, an equally legitimate public conversation could be had about shortening instead of lengthening the time frame for permitted research. </p>
<p>More importantly, there is no legitimate reason to have removed the 14-day rule in advance of any public engagement that might endorse the existing limit or advocate an alternative policy. Doing so changes the facts on paper and potentially also in practice.</p>
<p>For example, countries without relevant legislation, regulations or guidelines risk becoming havens for ethically controversial human embryo research beyond 14 days.</p>
<p>Indeed, the authors of the 2021 ISSCR guidelines boast that in jurisdictions where there is no legislation or where there are “substantial gaps and ambiguities” in the legislation “carefully constructed guidelines can play a critical role, for scientists and clinicians conducting research and treating patients.” The revised guidelines can no longer play this role for embryo research beyond 14 days.</p>
<h2>Changing science, limits</h2>
<p>Until recently, researchers were not able to maintain the human embryo in the lab beyond 14 days, and so the established limit had no practical effect. But in 2016, two research teams — one at the <a href="https://www.nature.com/articles/ncb3347">University of Cambridge in the U.K.</a> and the other at <a href="https://www.nature.com/articles/nature17948">Rockefeller University in the U.S.</a> — succeeded in maintaining human embryos in vitro for 12 to 13 days. They could have continued their experiments, but ended them in accordance with the 14-day rule. </p>
<p>The research conducted in the U.K. referenced the relevant legislation as the reason for concluding the experiments. The research conducted in the United States, where there is no relevant legislation, explicitly referenced the ISSCR guidelines. </p>
<p>Since then, debate in academic circles about the merits of the 14-day rule have intensified. Now that it is possible to overcome the technical limitations, some are intent on shifting the ethical limitations.</p>
<p>One suggestion is to “<a href="https://www.nature.com/articles/d41586-018-05586-z">keep the 14-day rule in place and have a special petition to make an exception</a>.” Another suggestion is to <a href="https://dx.doi.org/10.15252/emmm.201809437">extend the time limit to 28 days</a> to allow researchers to learn more about embryonic developmental processes.</p>
<p>My suggestion, as an ethicist who works at the intersection of policy and practice, is to have <a href="https://impactethics.ca/2016/05/05/pushing-the-14-day-limit-on-human-embryo-research/">project specific time limits</a> based on the minimum amount of time required to address the stated research objectives. This could mean that some human embryo research would not be allowed to continue to day 14, while other research might be allowed to continue beyond day 14. </p>
<p>Research categories with different time limits might be described in international or national research ethics guidelines and entrenched in national legislation. Alternatively, national regulations and guidelines might only stipulate the general intent, and project-specific decision-making might be at the discretion of a national specialized research ethics committee.</p>
<p>These suggestions for ethical limits on human embryo research — and others — require the public’s input. And while it is good to see the ISSCR promote public engagement, it is disappointing that this support should come at the price of the established international norm.</p><img src="https://counter.theconversation.com/content/161616/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Françoise Baylis is a member of the WHO Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing, a member of a Working Group to inform the development of the WHO Global Guidance Framework to Harness the Responsible Use of the Life Sciences, May to July 2021, and a member of Planning Committee for the Third International Summit on Human Genome Editing’, London, 7-9 March 2022.</span></em></p>In most countries, scientific research that uses human embryos has to halt after the 14th day. New guidelines recommend the public’s input in extending the time period.Françoise Baylis, Research Professor, Philosophy, Dalhousie UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1616112021-05-27T10:38:23Z2021-05-27T10:38:23ZGrowing human embryos in the lab and why scientists just tweaked the rules – podcast<figure><img src="https://images.theconversation.com/files/402947/original/file-20210526-21-1u5rsa0.jpg?ixlib=rb-1.1.0&rect=0%2C52%2C4865%2C3540&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Illustration of an early stage human embryo. </span> <span class="attribution"><span class="source">nobeastsofierce via Shutterstock</span></span></figcaption></figure><p>In this week’s episode of <a href="https://theconversation.com/uk/topics/the-conversation-weekly-98901">The Conversation Weekly</a>, as new scientific guidelines are released on embryo research and the use of stem cells, we talk to experts about what’s changed – including a recommendation to relax the 14-day time limit for human embryo research. And we hear about a wave of romantic comedy films emerging from South Africa that are re-imagining the city of Johannesburg. </p>
<iframe src="https://embed.acast.com/60087127b9687759d637bade/60af6da2a7e7e20012444626?cover=true" frameborder="0" allow="autoplay" width="100%" height="110"></iframe>
<p><iframe id="tc-infographic-561" class="tc-infographic" height="100" src="https://cdn.theconversation.com/infographics/561/4fbbd099d631750693d02bac632430b71b37cd5f/site/index.html" width="100%" style="border: none" frameborder="0"></iframe></p>
<p>It’s been five years since the last set of guidelines from the International Society for Stem Cell Research (ISSCR) were published. Since then, scientists have made significant developments in stem cell and embryo research – including the creation of <a href="https://theconversation.com/researchers-have-grown-human-embryos-from-skin-cells-what-does-that-mean-and-is-it-ethical-157228">human embryo models</a> and the <a href="https://theconversation.com/first-human-monkey-embryos-created-a-small-step-towards-a-huge-ethical-problem-159355">first human-monkey embryos</a>. </p>
<p>Now, <a href="https://www.isscr.org/policy/guidelines-for-stem-cell-research-and-clinical-translation">new ISSCR guidelines</a> have just been published. One of the most significant shifts concerns what’s called the 14-day rule. This has prohibited researchers – by law in some countries, <a href="https://www.legislation.gov.uk/ukpga/2008/22">such as the UK</a> – from growing human embryos in the lab for more than 14 days. The revised guidelines no longer strictly prohibit this, rather they recommend that a panel of experts should approve research proposals on a case-by-case basis. And they also call on countries to start national conversations about the issue and whether such research should be allowed.</p>
<p>The ISSCR guidelines are not international law, but their recommendations are used by countries around the world to guide their own national regulations and legislation. And also by countries that don’t have laws governing this kind of research using embryos and stem cells. </p>
<p>For this episode, we talk to Megan Munsie, deputy director for the Centre for Stem Cell Systems at the University of Melbourne and one of the scientists who sat on the panel that reviewed the guidelines. She tells us there have been advances that mean that we can now grow sperm-egg embryos for more than 14 days, “and the guideline is calling for consideration about whether we should”. She says that in a very small number of cases there may be justification for doing so.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/new-global-guidelines-for-stem-cell-research-aim-to-drive-discussions-not-lay-down-the-law-161578">New global guidelines for stem cell research aim to drive discussions, not lay down the law</a>
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</em>
</p>
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<p>The guidelines stress that doing research using human embryos should be a last resort – only turned to if there is no other way to get the same information. And this is where human embryo models come in. We speak to Jun Wu, assistant professor in molecular biology at the University of Texas Southwestern Medical Center, whose lab recently <a href="https://www.nature.com/articles/s41586-021-03356-y%C2%A0">made a breakthrough</a> by creating a human embryo model, called a blastoid, using human pluripotent stem cells. He explains how he did it and why this kind of research is so important to help understand what happens in the earliest stages of pregnancy, when the embryo implants into the womb lining. “This process of implantation is essentially a black box,” Wu says. “We don’t know much about it.” </p>
<p>And we speak to César Palacios-González senior research fellow in practical ethics at the Uehiro Centre for Practical Ethics at the University of Oxford, about some of the moral dilemmas that the 14-day rule and research using human embryos provoke. “Philosophers like myself love thinking about these things,” he told us. “The main ethical question that people have in mind is the moral value that human embryos have, and if actually we should even be carrying out this particular type of research.” He explains the arguments on both sides. </p>
<p>In our second story (at 25:20), we head to South Africa, where a wave of romantic comedies has hit the big screen in recent years. Many of these films are set in Johannesburg – a city that’s had a violent portrayal in film. Pier Paolo Frassinelli, professor of communication and media studies at the University of Johannesburg has <a href="https://www.tandfonline.com/doi/abs/10.1080/02533952.2021.1899734?journalCode=rsdy20">just published new research</a> looking at the way Black South African filmmakers are now portraying Joburg in a different light through these romcoms. “Even though the films try to present a certain image of upper-middle-class Johannesburg, the films cannot quite push away the tensions, the contradictions, the complexities of the city,” Frassinelli tells us. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/south-africas-romcom-revolution-and-how-it-reimagines-joburg-159255">South Africa's romcom revolution and how it reimagines Joburg</a>
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</em>
</p>
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<p>And Wale Fatade, commissioning editor at The Conversation in Lagos, Nigeria, gives us his recommended reading. </p>
<p>The Conversation Weekly is produced by Mend Mariwany and Gemma Ware, with sound design by Eloise Stevens. Our theme music is by Neeta Sarl. You can find us on Twitter <a href="https://twitter.com/TC_Audio">@TC_Audio</a>, on Instagram at <a href="https://www.instagram.com/theconversationdotcom/?hl=en">theconversationdotcom</a>. or via email on podcast@theconversation.com. You can also sign up to <a href="https://theconversation.com/newsletter?utm_campaign=PodcastTCWeekly&utm_content=newsletter&utm_source=podcast">The Conversation’s free daily email here</a>.</p>
<p>A transcript of this episode will be available soon. </p>
<p>News clips in this episode are from <a href="https://www.youtube.com/watch?v=GF1ZoSLMZVo">ABC News Australia</a>, <a href="https://www.youtube.com/watch?v=C9V3mqswbv0">AP News</a>, <a href="https://www.youtube.com/watch?v=oBMDMXDftnM">Rififi Pictures Trailer: Tell me Sweet Something</a>, <a href="https://www.youtube.com/watch?v=teS_BiLulVs">Showmax, Trailer: Happiness is a Four Letter Word</a>, <a href="https://www.youtube.com/watch?v=9gcty69_R74">Mrs Right Guy Official, Trailer: Mrs Right Guy</a>, <a href="https://www.youtube.com/watch?v=DyLUwOcR5pk">Sony Picture Entertainment: District 9 - Official Trailer</a> and <a href="https://www.youtube.com/watch?v=t6EohBg3QoY">Movieclips Classic Trailers, Trailer: Jerusalema</a>. </p>
<p><em>You can listen to The Conversation Weekly via any of the apps listed above, our <a href="https://feeds.acast.com/public/shows/60087127b9687759d637bade">RSS feed</a>, or find out how else to <a href="https://theconversation.com/how-to-listen-to-the-conversations-podcasts-154131">listen here</a>.</em></p><img src="https://counter.theconversation.com/content/161611/count.gif" alt="The Conversation" width="1" height="1" />
Plus, how a new wave of South African romcoms is reimagining Johannesburg. Listen to episode 17 of The Conversation Weekly podcast.Gemma Ware, Head of AudioDaniel Merino, Associate Breaking News Editor and Co-Host of The Conversation Weekly PodcastLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1578432021-04-22T12:25:43Z2021-04-22T12:25:43ZLab-grown embryos and human-monkey hybrids: Medical marvels or ethical missteps?<figure><img src="https://images.theconversation.com/files/396376/original/file-20210421-23-1cklx15.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1198%2C808&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Researchers have grown mammal embryos later into development than ever before in an artificial womb.</span> <span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Geometric_Progression.jpg#/media/File:Geometric_Progression.jpg">Vitalii Kyryk/WikimediaCommons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>In Aldous Huxley’s 1932 novel “<a href="https://www.oxfordreference.com/view/10.1093/oi/authority.20110803095525181">Brave New World</a>,” people aren’t born from a mother’s womb. Instead, embryos are grown in artificial wombs until they are brought into the world, a process called ectogenesis. In the novel, technicians in charge of the hatcheries manipulate the nutrients they give the fetuses to make the newborns fit the desires of society. Two recent scientific developments suggest that Huxley’s imagined world of functionally manufactured people is no longer far-fetched.</p>
<p>On March 17, 2021, an Israeli team announced that it had grown mouse embryos for 11 days – about half of the gestation period – in <a href="https://doi.org/10.1038/s41586-021-03416-3">artificial wombs</a> that were essentially bottles. Until this experiment, no one had grown a mammal embryo outside a womb this far into pregnancy. Then, on April 15, 2021, a U.S. and Chinese team announced that it had successfully grown, for the first time, <a href="https://doi.org/10.1016/j.cell.2021.03.020">embryos that included both human and monkey cells</a> in plates to a stage where organs began to form. </p>
<p>As both a <a href="https://scholar.google.com/citations?hl=en&user=wQsQxFoAAAAJ">philosopher and a biologist</a> I cannot help but ask how far researchers should take this work. While creating chimeras – the name for creatures that are a mix of organisms – might seem like the more ethically fraught of these two advances, ethicists think the medical benefits far outweigh the ethical risks. However, ectogenesis could have far-reaching impacts on individuals and society, and the prospect of babies grown in a lab has not been put under nearly the same scrutiny as chimeras.</p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/tNb2npuiF3Q?wmode=transparent&start=7" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Mouse embryos were grown in an artificial womb for 11 days, and organs had begun to develop.</span></figcaption>
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<h2>Growing in an artificial womb</h2>
<p>When in vitro fertilization first emerged in the late 1970s, the press called IVF embryos “test-tube babies,” though they are nothing of the sort. These embryos are implanted into the uterus within a day or two after doctors fertilize an egg in a petri dish.</p>
<p>Before the Israeli experiment, researchers had not been able to grow mouse embryos outside the womb for more than four days – providing the embryos with enough oxygen had been too hard. The team spent <a href="https://doi.org/10.1126/science.abi5734">seven years</a> creating a system of slowly spinning glass bottles and controlled atmospheric pressure that simulates the placenta and provides oxygen.</p>
<p>This development is a major step toward ectogenesis, and scientists expect that it will be possible to extend mouse development further, possibly <a href="https://www.technologyreview.com/2021/03/17/1020969/mouse-embryo-grown-in-a-jar-humans-next/">to full term outside the womb</a>. This will likely require new techniques, but at this point it is a problem of scale – being able to accommodate a larger fetus. This appears to be a <a href="http://hdl.handle.net/10822/547926">simpler challenge to overcome</a> than figuring out something totally new like supporting organ formation.</p>
<p>The Israeli team plans to <a href="https://www.technologyreview.com/2021/03/17/1020969/mouse-embryo-grown-in-a-jar-humans-next/">deploy its techniques on human embryos</a>. Since mice and humans have similar developmental processes, it is likely that the team will succeed in growing human embryos in artificial wombs. </p>
<p>To do so, though, members of the team need permission from their ethics board. </p>
<p>CRISPR – a technology that can cut and paste genes – already allows scientists to manipulate an embryo’s genes after fertilization. Once fetuses can be grown outside the womb, as in Huxley’s world, researchers will also be able to modify their growing environments to further influence what <a href="https://doi.org/10.1093/jn/134.9.2169">physical and behavioral qualities these parentless babies exhibit</a>. Science still has a way to go before fetus development and births outside of a uterus become a reality, but researchers are getting closer. The question now is how far humanity should go down this path.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/396377/original/file-20210421-21-17un52t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A drawing of a half–eagle, half–horse griffin." src="https://images.theconversation.com/files/396377/original/file-20210421-21-17un52t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/396377/original/file-20210421-21-17un52t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=634&fit=crop&dpr=1 600w, https://images.theconversation.com/files/396377/original/file-20210421-21-17un52t.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=634&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/396377/original/file-20210421-21-17un52t.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=634&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/396377/original/file-20210421-21-17un52t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=797&fit=crop&dpr=1 754w, https://images.theconversation.com/files/396377/original/file-20210421-21-17un52t.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=797&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/396377/original/file-20210421-21-17un52t.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=797&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Chimeras evoke images of mythological creatures of multiple species – like this 15th-century drawing of a griffin – but the medical reality is much more sober.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Martin_Schongauer,_The_griffin_(15th_century).jpg#/media/File:Martin_Schongauer,_The_griffin_(15th_century).jpg">Martin Schongauer/WikimediaCommons</a></span>
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</figure>
<h2>Human-monkey hybrids</h2>
<p>Human–monkey hybrids might seem to be a much scarier prospect than babies born from artificial wombs. But in fact, the recent research is more a step toward an important medical development than an ethical minefield.</p>
<p>If scientists can grow human cells in monkeys or other animals, it should be possible to <a href="https://doi.org/10.1016/j.cell.2021.03.044">grow human organs</a> too. This would solve the problem of <a href="https://www.bbc.com/news/science-environment-56767517">organ shortages</a> around the world for people needing transplants.</p>
<p>But keeping human cells alive in the embryos of other animals for any length of time has proved to be extremely difficult. In the <a href="https://doi.org/10.1016/j.cell.2021.03.020">human-monkey chimera experiment</a>, <a href="https://www.bbc.com/news/science-environment-56767517">a team of researchers implanted</a> 25 human stem cells into embryos of crab-eating macaques – a type of monkey. The researchers then <a href="https://doi.org/10.1016/j.cell.2021.03.044">grew these embryos</a> for 20 days in petri dishes.</p>
<p>After 15 days, the human stem cells had disappeared from most of the embryos. But at the end of the 20-day experiment, three embryos still contained human cells that had grown as part of the region of the embryo where they were embedded. For scientists, the challenge now is to figure out how to maintain human cells in chimeric embryos for longer.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/396400/original/file-20210421-17-162zdc2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A drawing of test tubes with embryos inside." src="https://images.theconversation.com/files/396400/original/file-20210421-17-162zdc2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/396400/original/file-20210421-17-162zdc2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/396400/original/file-20210421-17-162zdc2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/396400/original/file-20210421-17-162zdc2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/396400/original/file-20210421-17-162zdc2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/396400/original/file-20210421-17-162zdc2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/396400/original/file-20210421-17-162zdc2.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>
<figcaption>
<span class="caption">The ability to grow true test–tube babies raises many ethical questions.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/conceptual-image-of-human-cloning-royalty-free-image/1287023975?adppopup=true">Carol Yepes/Moment via Getty Images</a></span>
</figcaption>
</figure>
<h2>Regulating these technologies</h2>
<p>Some ethicists have begun to worry that researchers are <a href="https://doi.org/10.1016/j.cell.2021.03.044">rushing into a future</a> of chimeras without adequate preparation. Their main concern is the <a href="https://www.bbc.com/news/science-environment-56767517">ethical status of chimeras</a> that contain human and nonhuman cells – especially if the human cells integrate into sensitive regions <a href="https://doi.org/10.1016/j.cell.2021.03.044">such as a monkey’s brain</a>. What rights would such creatures have?</p>
<p>However, there seems to be an emerging consensus that the potential medical benefits justify a step-by-step extension of this research. Many ethicists are urging <a href="https://doi.org/10.1016/j.cell.2021.03.044">public discussion</a> of appropriate regulation to determine how close to viability these embryos should be grown. One proposed solution is to limit growth of these embryos to the first trimester of pregnancy. Given that researchers don’t plan to grow these embryos beyond the stage when they can <a href="https://doi.org/10.1016/j.cell.2021.03.044">harvest rudimentary organs</a>, I don’t believe chimeras are ethically problematic compared with the true test–tube babies of Huxley’s world.</p>
<p>Few ethicists have broached the problems posed by the ability to use ectogenesis to engineer human beings to fit societal desires. Researchers have yet to conduct experiments on human ectogenesis, and for now, scientists lack the techniques to bring the embryos to full term. However, without regulation, I believe researchers are likely to try these techniques on human embryos – just as the now-infamous He Jiankui <a href="https://thehill.com/opinion/healthcare/422891-how-we-proceed-with-human-gene-editing-will-be-the-debate-of-the-future">used CRISPR to edit human babies</a> without properly assessing safety and desirability. Technologically, it is a matter of time before mammal embryos can be brought to term outside the body. </p>
<p>[<em>Over 100,000 readers rely on The Conversation’s newsletter to understand the world.</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=100Ksignup">Sign up today</a>.]</p>
<p>While people may be uncomfortable with ectogenesis today, this discomfort could pass into familiarity as happened with IVF. But scientists and regulators would do well to reflect on the wisdom of permitting a process that could allow someone to engineer human beings without parents. As <a href="https://doi.org/10.1002/j.1552-146x.2011.tb00098.x">critics have warned</a> in the context of CRISPR-based genetic enhancement, pressure to change future generations to meet societal desires will be unavoidable and dangerous, regardless of whether that pressure comes from an authoritative state or cultural expectations. In Huxley’s imagination, hatcheries run by the state grew a large numbers of identical individuals as needed. That would be a very different world from today.</p><img src="https://counter.theconversation.com/content/157843/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sahotra Sarkar 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>Researchers have grown the first human-monkey hybrid embryos as well as mouse embryos in artificial wombs late into development. These biomedical breakthroughs raise different ethical quandaries.Sahotra Sarkar, Professor of Philosophy and Integrative Biology, The University of Texas at AustinLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1504962020-12-15T13:20:28Z2020-12-15T13:20:28ZVirgin births from parthenogenesis: How females from some species can reproduce without males<figure><img src="https://images.theconversation.com/files/374837/original/file-20201214-17-2nde3j.png?ixlib=rb-1.1.0&rect=0%2C0%2C5463%2C3006&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Getting the job done. A female Asian water dragon (Physignathus cocincinus) produced a daughter (left) without the assistance of a male. </span> <span class="attribution"><a class="source" href="https://nationalzoo.si.edu/news/scientists-confirm-facultative-parthenogenesis-smithsonians-national-zoos-asian-water-dragon">Skip Brown/Smithsonian’s National Zoo</a></span></figcaption></figure><p>An Asian water dragon hatched from an egg at the Smithsonian National Zoo, and her keepers were shocked. Why? Her mother had never been with a male water dragon. Through genetic testing, zoo scientists discovered the newly hatched female, born on Aug. 24, 2016, had been produced through a <a href="https://doi.org/10.1371/journal.pone.0217489">reproductive mode called parthenogenesis</a>.</p>
<p>Parthenogenesis is a Greek word meaning “virgin creation,” but specifically refers to female asexual reproduction. While many people may assume this behavior is the domain of science fiction or religious texts, parthenogenesis is <a href="https://doi.org/10.1038/sdata.2014.15">surprisingly common throughout the tree of life</a> and is found in a variety of organisms, including plants, insects, fish, reptiles and even birds. Because mammals, including human beings, require certain genes to come from sperm, <a href="https://doi.org/10.1159/000090812">mammals are incapable of parthenogenesis</a>.</p>
<h2>Creating offspring without sperm</h2>
<p>Sexual reproduction involves a female and a male, each contributing genetic material in the form of eggs or sperm, to create a unique offspring. The vast majority of animal species reproduce sexually, but females of some species are able to produce eggs <a href="https://www.britannica.com/science/parthenogenesis">containing all the genetic material required for reproduction</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/373966/original/file-20201209-19-1x4523.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A microscopic view of a translucent water flea show four round eggs inside." src="https://images.theconversation.com/files/373966/original/file-20201209-19-1x4523.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/373966/original/file-20201209-19-1x4523.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=418&fit=crop&dpr=1 600w, https://images.theconversation.com/files/373966/original/file-20201209-19-1x4523.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=418&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/373966/original/file-20201209-19-1x4523.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=418&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/373966/original/file-20201209-19-1x4523.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=526&fit=crop&dpr=1 754w, https://images.theconversation.com/files/373966/original/file-20201209-19-1x4523.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=526&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/373966/original/file-20201209-19-1x4523.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=526&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 female freshwater water flea (<em>Daphnia magna</em>) carrying parthenogenetic eggs.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/microscopic-view-of-freshwater-water-flea-royalty-free-image/841300586">buccaneership/iStock via Getty Images Plus</a></span>
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<p>Females of these species, which include <a href="https://doi.org/10.1002/evl3.30">some wasps</a>, <a href="https://doi.org/10.1086/283761">crustaceans</a> and <a href="https://www.scientificamerican.com/article/asexual-lizards/">lizards</a>, reproduce only through parthenogenesis and are called obligate parthenogens.</p>
<p>A larger number of species experience spontaneous parthenogenesis, best documented in animals kept in zoo settings, like the Asian water dragon at the National Zoo or a <a href="https://doi.org/10.1111/j.1095-8649.2008.02018.x">blacktip shark at the Virginia Aquarium</a>. Spontaneous parthenogens typically reproduce sexually, but may have occasional cycles that produce developmentally ready eggs.</p>
<p>Scientists have learned <a href="https://doi.org/10.1098/rspb.2009.2113">spontaneous parthenogenesis may be a heritable trait</a>, meaning females that suddenly experience parthenogenesis might be more likely to have daughters that can do the same.</p>
<h2>How can females fertilize their own eggs?</h2>
<p>For parthenogenesis to happen, <a href="https://doi.org/10.1534/g3.112.005421">a chain of cellular events must successfully unfold</a>. First, females must be able to create egg cells (oogenesis) without stimulation from sperm or mating. Second, the eggs produced by females need to begin to develop on their own, forming an early stage embryo. Finally, the eggs must successfully hatch. </p>
<p>Each step of this process can easily fail, particularly step two, which requires the chromosomes of DNA inside the egg to double, ensuring a full complement of genes for the developing offspring. Alternatively, the egg can be “faux fertilized” by leftover cells from the egg production process known as <a href="https://doi.org/10.1002/mrd.21266">polar bodies</a>. Whichever method kicks off the development of the embryo <a href="https://doi.org/10.1525/bio.2009.59.7.3">will ultimately determine the level of genetic similarity</a> between the mother and her offspring.</p>
<p>The events that trigger parthenogenesis are not fully understood, but appear to include environmental change. In species that are capable of both sexual reproduction and parthenogenesis, such as <a href="https://doi.org/10.1371/journal.pone.0115099">aphids</a>, stressors like <a href="https://doi.org/10.1111/een.12080">crowding and predation</a> may cause females to switch from parthenogenesis to sexual reproduction, but not the other way around. In at least one <a href="https://doi.org/10.1007/978-90-481-2770-2_15">type of freshwater plankton</a>, <a href="https://doi.org/10.5762/KAIS.2016.17.4.692">high salinity</a> appears to cause the switch.</p>
<h2>Advantages of self-reproduction</h2>
<p>Though spontaneous parthenogenesis appears to be rare, it does provide some benefits to the female who can achieve it. In some cases, it can allow females to generate their own mating partners. </p>
<p>The sex of parthenogenetic offspring is determined by the same method sex is determined in the species itself. For organisms where sex is determined by chromosomes, like the XX female and XY male chromosomes in some insects, fish and reptiles, a parthenogenetic female can produce offspring only with the sex chromosomes she has at hand – which means she will always produce XX female offspring. But for organisms where females have ZW sex chromosomes (such as in snakes and birds), all living offspring produced will either be ZZ, and therefore male, or <a href="https://doi.org/10.1098/rsbl.2010.0793">much more rarely, WW, and female</a>.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"976632933531316224"}"></div></p>
<p>Between 1997 and 1999, <a href="https://doi.org/10.1111/j.1095-8312.2012.01954.x">a checkered gartersnake kept at the Phoenix Zoo</a> gave birth to two male offspring that ultimately survived to adulthood. If a female mated with her parthenogenetically produced son, it would constitute inbreeding. While inbreeding can result in a host of genetic problems, from an evolutionary perspective it’s better than having no offspring at all. The ability of females to produce male offspring through parthenogenesis also suggests that asexual reproduction in nature may be more common than scientists ever realized before. </p>
<p>Biologists have observed, over long periods of time, that <a href="https://doi.org/10.1016/0022-5193(71)90058-0">species that are obligate parthenogens frequently die out</a> from <a href="https://doi.org/10.1038/s41514-018-0025-3">disease</a>, <a href="https://doi.org/10.1073/pnas.87.9.3566">parasitism</a> or <a href="https://doi.org/10.1002/evl3.30">changes in habitat</a>. The inbreeding inherent in parthenogenetic species appears to contribute to their short evolutionary timelines. </p>
<p>Current research on parthenogenesis seeks to understand why some species are capable of both sex and parthenogenesis, and whether occasional sexual reproduction might be enough for a species to survive.</p><img src="https://counter.theconversation.com/content/150496/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mercedes Burns has previously received funding from the National Science Foundation. </span></em></p>Parthenogenesis, a form of reproduction in which an egg develops into an embryo without being fertilized by sperm, might be more common than you realized.Mercedes Burns, Assistant Professor of Biological Sciences, University of Maryland, Baltimore CountyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1268392019-11-25T01:12:12Z2019-11-25T01:12:12ZGenetic testing IVF embryos doesn’t improve the chance of a baby<figure><img src="https://images.theconversation.com/files/302547/original/file-20191119-111663-1cc8lwc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Genetic testing costs around A$700 per embryo.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/new-born-baby-boy-resting-mothers-663728050">KieferPix</a></span></figcaption></figure><p>If you’re going through IVF, you may be offered a test to look at your embryos’ chromosomes. </p>
<p><a href="https://www.fertstert.org/article/S0015-0282(19)32454-9/fulltext">Pre-implantation genetic testing</a> for aneuploidy (chromosome abnormalities), known as PGT-A, is an “add on” used to help choose embryos with the right number of chromosomes. It’s promoted by IVF clinics as a way to increase the chance of success, especially for women over 35. </p>
<p>But the <a href="https://www.ncbi.nlm.nih.gov/pubmed/30085138">evidence shows</a> that in most cases, PGT-A doesn’t improve the chance of a baby.</p>
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Read more:
<a href="https://theconversation.com/the-business-of-ivf-how-human-eggs-went-from-simple-cells-to-a-valuable-commodity-119168">The business of IVF: how human eggs went from simple cells to a valuable commodity</a>
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<h2>What is aneuploidy?</h2>
<p>Human cells usually contain 46 chromosomes. Aneuploidy is a term that describes a chromosome number that is different from 46 – either too many or too few chromosomes. </p>
<p>In human embryos, most aneuploidies are lethal, resulting in miscarriage, or do not result in pregnancy at all. </p>
<p>The chance of aneuploidy increases with the age of the woman; by the time a woman reaches age 40, <a href="https://journals.sagepub.com/doi/full/10.1177/2058915816653277">approximately 80%</a> of her embryos are aneuploid. </p>
<h2>What is PGT-A?</h2>
<p>All couples produce some aneuploid embryos, whether they conceive naturally or with IVF. The idea behind PGT-A is that if the aneuploid embryos can be identified they can be discarded, so that only embryos capable of producing a healthy pregnancy are used. </p>
<p>PGT-A involves the woman having fertility drugs to produce several eggs. When they are mature, they are retrieved and mixed with sperm to create embryos. </p>
<p>Embryos are grown in the laboratory for five to six days. At this time, two types of cells are distinguishable: the cells that will develop into the placenta and the cells that will become the baby. </p>
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<strong>
Read more:
<a href="https://theconversation.com/considering-using-ivf-to-have-a-baby-heres-what-you-need-to-know-108910">Considering using IVF to have a baby? Here's what you need to know</a>
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<p>A few cells are removed from the future placenta for testing and the embryos are frozen until test results are available. </p>
<p>If the test shows there are normal embryos, one is thawed and transferred to the woman’s uterus. Any remaining normal embryos will be kept frozen for transfer later if the first transfer is unsuccessful. </p>
<p>Importantly, PGT-A doesn’t “correct” chromosomally abnormal embryos, it simply allows couples to avoid transferring them.</p>
<h2>Who might be offered PGT-A?</h2>
<p>Many clinics recommend PGT-A for women over 35 (<a href="https://npesu.unsw.edu.au/sites/default/files/npesu/data_collection/Assisted%20Reproductive%20Technology%20in%20Australia%20and%20New%20Zealand%202017.pdf">more than half of women who have IVF</a>) and those who have had repeated miscarriages or failed IVF treatments. This is because women over 35 and women with previous losses are more likely to produce aneuploid embryos. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/302799/original/file-20191121-502-z5l5id.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/302799/original/file-20191121-502-z5l5id.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/302799/original/file-20191121-502-z5l5id.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/302799/original/file-20191121-502-z5l5id.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/302799/original/file-20191121-502-z5l5id.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/302799/original/file-20191121-502-z5l5id.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/302799/original/file-20191121-502-z5l5id.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">Women over 35 are more likely to have embryos with chromosomal abnormalities than younger women.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/510591736?src=f8b1f75f-c3ae-4a42-8efa-9e5cf579abc3-1-20&size=huge_jpg">Natalia Lebedinskaia/Shutterstock</a></span>
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<h2>Does PGT-A work?</h2>
<p>While the theory behind PFT-A makes sense, randomised controlled trials (the gold standard evidence to tell us if an intervention makes a difference) have not demonstrated a clear benefit. </p>
<p>Of the two <a href="https://www.ncbi.nlm.nih.gov/pubmed/30085138">most recent trials</a> of PGT-A, one reported fewer embryo transfers and fewer miscarriages in the PGT-A group but <a href="https://www.ncbi.nlm.nih.gov/pubmed/31551155">neither showed benefits</a> in terms of improving the live-birth rate. </p>
<h2>The pitfalls of PGT-A</h2>
<p>PGT-A actually has the potential to <em>reduce</em> <a href="https://doi.org/10.1111/ajo.12960">the chance of a baby</a>. It can do this in two ways. </p>
<p>First, <a href="https://doi.org/10.1111/ajo.12960">PGT-A is not 100% accurate</a>. This means that inevitably, some embryos that have the capacity to form a healthy baby will be discarded. </p>
<p>The most common reason for these “false positive” results is that a proportion of embryos are “mosaic” – they have a mix of normal and abnormal cells. Surprisingly, mosaic chromosome abnormalities are <a href="https://www.rbmojournal.com/article/S1472-6483(19)30599-1/fulltext">quite common</a> in early human embryos, and do not seem to prevent the embryo developing into a healthy baby. </p>
<p>However, if abnormal cells are removed and tested, the embryo will be misclassified as abnormal and discarded – a lost opportunity for a healthy pregnancy. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/fertility-miracle-or-fake-news-understanding-which-ivf-add-ons-really-work-118585">Fertility miracle or fake news? Understanding which IVF 'add-ons' really work</a>
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<p><a href="https://www.ncbi.nlm.nih.gov/pubmed/31236830">Many healthy babies have been born</a> to people who have elected to have mosaic embryos transferred because they were the only embryos they had. </p>
<p>In a <a href="https://doi.org/10.1016/j.fertnstert.2018.10.001">recent study of 98 women</a> who had mosaic embryos, 32 (33%) elected to have at least one transferred. Of these, 11 (34%) had a successful pregnancy with apparently healthy babies born.</p>
<p>Second, while the <a href="https://www.fertstert.org/article/S0015-0282(18)30002-5/fulltext">risk is small</a>, embryos can be damaged in the biopsy procedure and some embryos don’t survive the freezing and thawing process. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/302800/original/file-20191121-474-1o2hsdf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/302800/original/file-20191121-474-1o2hsdf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=407&fit=crop&dpr=1 600w, https://images.theconversation.com/files/302800/original/file-20191121-474-1o2hsdf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=407&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/302800/original/file-20191121-474-1o2hsdf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=407&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/302800/original/file-20191121-474-1o2hsdf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=512&fit=crop&dpr=1 754w, https://images.theconversation.com/files/302800/original/file-20191121-474-1o2hsdf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=512&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/302800/original/file-20191121-474-1o2hsdf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=512&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Some women elect to have mosaic embryos transferred.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/749056846?src=ea47bcd4-7675-4022-927d-8b4cff73b144-1-14&size=huge_jpg">Rawpixel.com/Shutterstock</a></span>
</figcaption>
</figure>
<h2>To have or not to have PGT-A?</h2>
<p>PGT-A costs around A$700 per embryo which adds up to A$2,800 if there are four embryos to test.</p>
<p>While doctors likely offer their patients detailed and individualised information about different treatment options, information about the possible benefits of PGT-A on clinic websites can be difficult to interpret. </p>
<p>That’s why independent information about the pros and cons of PGT-A is needed to help people make informed decisions. The Victorian Assisted Reproductive Treatment Authority (VARTA) has developed a <a href="https://www.varta.org.au/resources/publications/pros-and-cons-pre-implantation-genetic-testing-aneuploidy-pgt">downloadable resource</a> about the current state of knowledge about PGT-A. </p>
<p>Some clinics are now offering a less invasive technique where, rather than removing cells from the embryo, they test the fluid that the embryo is grown in to <a href="https://www.pnas.org/content/116/28/14105.short">determine if the embryo has the right number of chromosomes</a>. Time will tell of this will improve the chance of having a baby with IVF. </p>
<p>In the meantime, it may help to ask the five questions recommended by <a href="http://www.choosingwisely.org.au/resources/consumers/5-questions-to-ask-your-doctor">Choosing Wisely</a>: </p>
<ul>
<li>do I really need this test?</li>
<li>what are the risks?</li>
<li>are there safer, simpler options?</li>
<li>what happens if I don’t do anything?</li>
<li>what are the costs?</li>
</ul>
<p>And in the case of IVF: how will this improve my chance of a live birth?</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/your-questions-answered-on-donor-conception-and-ivf-45715">Your questions answered on donor conception and IVF</a>
</strong>
</em>
</p>
<hr>
<img src="https://counter.theconversation.com/content/126839/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Karin Hammarberg is affiliated with the Victorian Assisted Reproductive Treatment Authority.</span></em></p><p class="fine-print"><em><span>David Amor 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>Women aged over 35 are sometimes offered genetic testing of their IVF embryos to rule out abnormalities. But it’s expensive and doesn’t increase their chance of a baby. In fact, it could reduce it.Karin Hammarberg, Senior Research Fellow, Global and Women's Health, School of Public Health & Preventive Medicine, Monash UniversityDavid Amor, Lorenzo and Pamela Galli Chair in Developmental Medicine, Murdoch Children's Research InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1208932019-09-19T20:54:00Z2019-09-19T20:54:00ZWhy do men have nipples?<figure><img src="https://images.theconversation.com/files/288881/original/file-20190821-170941-jihsap.jpg?ixlib=rb-1.1.0&rect=0%2C14%2C3333%2C3313&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Men have nipples because of a quirk in how embryos develop. But that's only part of the story of this seemingly redundant body part.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/nipple-323037320?src=Ztai78yG_qxfTkWQusy-Hg-1-12">from www.shutterstock.com</a></span></figcaption></figure><p>Women’s nipples have long been a source of fascination and controversy, from celebrity gossip stories of wardrobe malfunctions and “<a href="https://www.cosmopolitan.com/entertainment/celebs/news/g4657/celebrity-nip-slips/">nip slips</a>” to feminist movements for <a href="https://www.telegraph.co.uk/women/womens-life/10880647/Topless-women-campaign-to-Free-The-Nipple-why-on-earth-do-women-want-to-walk-around-topless-in-public.html">gender equality</a>. Nipples even became a <a href="https://www.thesun.co.uk/living/3341970/more-and-more-women-are-wearing-fake-nipples-and-they-come-in-sizes-ranging-from-cold-to-freezing/">fashion accessory</a>. </p>
<p>Men’s nipples are a different story. While they don’t tend to attract the same type of controversy, people have <a href="https://www.google.com/search?client=firefox-b-d&q=why+do+men+have+nipples%3F">long been fascinated</a> about why men have them. The question even made it into a popular science <a href="https://www.penguinrandomhouse.com/books/101277/why-do-men-have-nipples-by-mark-leyner-and-billy-goldberg-md/9781400082315/">book</a>.</p>
<p>So, if (most) men don’t breastfeed, why do men have nipples? The answer lies partly in how we develop in the womb. We’ll get to male breast milk later.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/no-youre-not-hardwired-to-stare-at-womens-breasts-53449">No, you’re not 'hardwired' to stare at women’s breasts</a>
</strong>
</em>
</p>
<hr>
<h2>A long time ago, when you were an embryo …</h2>
<p>Very early in development, embryos of both sexes have primitive structures that can develop into <a href="https://www.nature.com/scitable/topicpage/genetic-mechanisms-of-sex-determination-314/">either male or female reproductive organs</a> (or rarely into a bit of both).</p>
<p>Several genes determine whether the baby ends up with either male or female reproductive organs. A gene called <a href="https://ghr.nlm.nih.gov/gene/SRY">SRY</a> (sex-determining region Y) on the short arm of the Y chromosome is considered the master gene.</p>
<p>This is activated when the embryo is around seven weeks old. When activated, it eventually leads to the development of male reproductive organs and the disappearance of the primitive female reproductive duct. </p>
<p>As females don’t have a Y chromosome, the primitive female reproductive duct continues to develop into female reproductive organs while the primitive <a href="https://www.nature.com/scitable/topicpage/genetic-mechanisms-of-sex-determination-314/">male reproductive duct disappears</a>.</p>
<p>But breasts and nipples start to form <em>before</em> the SRY gene has been activated, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3706056/">between weeks four and six</a>. This is when two ridges called mammary crests or milk lines extend between the primitive armpit and the groin. </p>
<p>So, later in male development, even as most of the mammary crest disappears, the cells around the chest that form primitive nipples and areola smooth muscle remain. These remaining cells go on to form the final breasts and nipples.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/289768/original/file-20190828-184217-ln6st6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/289768/original/file-20190828-184217-ln6st6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/289768/original/file-20190828-184217-ln6st6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/289768/original/file-20190828-184217-ln6st6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/289768/original/file-20190828-184217-ln6st6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/289768/original/file-20190828-184217-ln6st6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/289768/original/file-20190828-184217-ln6st6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/289768/original/file-20190828-184217-ln6st6.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>
<figcaption>
<span class="caption">At around seven weeks, a critical gene is activated that puts embryos on the path to being male or female. But by then, critical cells that go on to become breasts and nipples have already developed.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/1110267386?src=-1-1&size=medium_jpg">from www.shutterstock.com</a></span>
</figcaption>
</figure>
<h2>Once you’re born</h2>
<p>At birth, boys’ and girls’ nipples and breasts look alike. It’s only at puberty, under the influence of hormones, when they begin to change. The nipples of both enlarge but female nipples enlarge more. At the same time, the ducts of the male breasts shrink while female breasts enlarge and remodel. By adulthood, male <a href="https://link.springer.com/article/10.1007/s40750-018-0096-1">nipples are smaller and less variable</a> than female ones.</p>
<p>From an evolutionary standpoint, <a href="https://www.tandfonline.com/doi/abs/10.1080/14681990600674674?scroll=top&needAccess=true&journalCode=csmt20">some argue</a> male nipples remain, not because they present any advantages for a male, but because they do no harm. There is no benefit in eliminating them.</p>
<h2>When development goes wrong</h2>
<p>Sometimes, as with any other body structures, development can go wrong. <a href="https://www.ncbi.nlm.nih.gov/pubmed/9809822">Around one in 20</a> people have supernumerary (or extra) nipples. This occurs when parts of the mammary crest remain. Often these nipples are purely cosmetic and resemble nothing more than a small pigmented mole. Only rarely are they fully functional. The highest number of nipples ever recorded on a human male is <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3656534/">seven</a>.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/an-extra-organ-or-body-part-is-more-common-than-you-think-76523">An extra organ or body part is more common than you think</a>
</strong>
</em>
</p>
<hr>
<h2>Some men can produce milk</h2>
<p>Intriguingly, sometimes males <a href="https://www.scientificamerican.com/article/strange-but-true-males-can-lactate/">can produce milk</a>. In many cases, this may be caused by recovery from <a href="https://www.ncbi.nlm.nih.gov/pubmed/19100649">starvation</a>, medical conditions that cause <a href="http://www.cmaj.ca/content/182/6/591">hormonal imbalances</a>, or <a href="https://www.aafp.org/afp/2004/0801/p543.html">medications</a>. The milk men produce in these circumstances is <a href="https://www.ncbi.nlm.nih.gov/pubmed/7462406">very similar</a> to that of lactating mothers. </p>
<h2>How do men benefit from having nipples?</h2>
<p>Unless you’re one of the rare men who can use their nipples to breastfeed, men benefit from this seemingly redundant body part for a much more common reason.</p>
<p>Nipples <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=Reports+of+intimate+touch%3A+Erogenous+zones+and+somatosensory+cortical+orga-nization">respond to sexual stimulation</a> in both sexes. One study found <a href="https://www.ncbi.nlm.nih.gov/pubmed/16681470">over half the male participants</a> reported feeling enhanced sexual arousal in response to nipple stimulation. There is even <a href="https://www.ncbi.nlm.nih.gov/pubmed/2337382">one report</a> describing a heterosexual man who requested breast enlargement to increase sexual function of his nipples. </p>
<h2>How about ‘man boobs’?</h2>
<p>But for some men, breast enlargement can be the unexpected consequence of being <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5758064/">overweight or obese</a>. And as we are seeing more obesity in western populations, we’re seeing a rise in “man breasts” or “man boobs”, which are mostly being made up of fat deposits. </p>
<p>Breast enlargement in men, or <a href="https://www.mayoclinic.org/diseases-conditions/gynecomastia/symptoms-causes/syc-20351793">gynaecomastia</a>, can also be caused by a hormone imbalance with a relative excess of oestrogens (female hormones) compared to androgens (male hormones). This mostly affects adolescent boys and usually resolves on its own, although it can persist in as many as <a href="https://www.ncbi.nlm.nih.gov/pubmed/26408934">one in 10 men</a>. In these cases, it can be associated with <a href="https://www.ncbi.nlm.nih.gov/pubmed/26408934">depression, anxiety, disordered eating, body image problems and reduced self-esteem</a>.</p>
<h2>Men get breast cancer too</h2>
<p>Unusually, men can develop <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/j.1610-0387.2011.07720.x">breast cancer</a> and it can have serious consequences.</p>
<p>Only <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351429/">0.5-1%</a> of all breast cancers are diagnosed in men. However, lower awareness of the disease in men means it is more likely to be at an advanced stage when diagnosed. That’s why lumps and changes in men’s nipples (for example, nipple discharge or skin ulcerations such as cracks in the skin), should be checked by a doctor to rule out cancers.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/breast-cancer-campaigns-might-be-pink-but-men-get-it-too-56663">Breast cancer campaigns might be pink, but men get it too</a>
</strong>
</em>
</p>
<hr>
<p>As we’ve seen, men’s nipples deserve as much attention as women’s nipples. Although, this is unlikely to distract the celebrity gossip columnists from their selective obsession with this part of the female anatomy.</p><img src="https://counter.theconversation.com/content/120893/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michelle Moscova 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>How embryos develop, evolution and sexual pleasure all help explain why men have nipples. But ‘man boobs’ are a different story.Michelle Moscova, Senior Lecturer in Anatomy, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1219122019-08-15T11:14:47Z2019-08-15T11:14:47ZWhat’s the right way for scientists to edit human genes? 5 essential reads<figure><img src="https://images.theconversation.com/files/288064/original/file-20190814-136222-xtmn4o.jpg?ixlib=rb-1.1.0&rect=431%2C449%2C5290%2C3520&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Ethical frameworks, rules, laws: all try to have their say.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/doctor-prepares-special-media-growing-embryos-1447342460?src=XFXBbEV0tU5iihvrK1Vv0A-1-12">Tati9/Shutterstock.com</a></span></figcaption></figure><p>Since scientists first figured out how to edit genes with precision using a technology called CRISPR, they’ve been grappling with when and how to do it ethically. Is it reasonable to edit human genes with CRISPR? What about human genes in reproductive cells that pass the edits on to future generations?</p>
<p>The <a href="http://nationalacademies.org/gene-editing/international-commission/index.htm?_ga=2.266036175.1969896713.1565792406-1004430421.1565792406">International Commission on the Clinical Use of Human Germline Genome Editing</a> convened on Aug. 13 to hash out guidelines about editing human embryos. The goal is to provide a framework that researchers around the globe can consult to ensure their work is in line with scientific consensus.</p>
<p>An earlier U.S. National Academies committee had already released recommendations in 2017. They called for caution – but were ambiguous enough for Chinese scientist He Jiankui to suggest he’d followed them even as he produced <a href="https://theconversation.com/how-a-scientist-says-he-made-a-gene-edited-baby-and-what-health-worries-may-ensue-107764">twin girls with CRISPR-edited genomes</a> late last year.</p>
<p>Here are five stories from our archive that explore how to ethically develop and regulate a potentially risky new technology.</p>
<h2>1. A voluntary pause</h2>
<p>No one denies the power of the CRISPR editing tool. It could allow doctors to one day cure genetic diseases, whether in adults who are living with medical conditions or in embryos that have not yet even been born. But there’s a lot of lab work yet to be done, as well as many conversations to be had, about the right way to proceed.</p>
<p>In 2015, a group of prominent scientists called for a voluntary freeze on germline editing – that is, changing sperm, eggs or embryos – until ethical issues could be resolved.</p>
<p>Chemical biologist <a href="https://theconversation.com/profiles/jeff-bessen-174263">Jeff Bessen</a> wrote that this approach has precedents in the scientific community, where many think it makes sense to take things slow and place “the right emphasis on <a href="https://theconversation.com/crispr-cas-gene-editing-technique-holds-great-promise-but-research-moratorium-makes-sense-pending-further-study-43371">safety and ethics without hampering research progress</a>.”</p>
<h2>2. Stringent hurdles before proceeding</h2>
<p>The National Academies’ 2017 report was meant to provide the scientific community with definitive guidance on the issue.</p>
<p><a href="https://theconversation.com/profiles/rosa-castro-303464">Rosa Castro</a>, a scholar of science and society, explained that the report gave the green light to modifying body cells and a yellow light to modifying reproductive cells that would allow the changes to be inherited by future progeny. The report’s goal was to ensure that “germline genome editing <a href="https://theconversation.com/safe-and-ethical-ways-to-edit-the-human-genome-73110">will be used only</a> to prevent a serious disease, where no reasonable alternatives exist, and under strong supervision.”</p>
<h2>3. Science marches on</h2>
<p>By later that year, a research group announced they’d successfully used CRISPR to modify human embryos, though the edited embryos weren’t implanted in women and were never born. Bioethics and public health professor <a href="https://scholar.google.com/citations?user=eXQqA5gAAAAJ&hl=en&oi=ao">Jessica Berg</a> wrote about the importance of <a href="https://theconversation.com/editing-human-embryos-with-crispr-is-moving-ahead-nows-the-time-to-work-out-the-ethics-81732">working out the ethical issues</a> of gene editing before researchers take the critical step of allowing modified embryos to develop and be born as babies.</p>
<blockquote>
<p>“Should there be limits on the types of things you can edit in an embryo? If so, what should they entail? These questions also involve deciding who gets to set the limits and control access to the technology.</p>
<p>"We may also be concerned about who gets to control the subsequent research using this technology. Should there be state or federal oversight? Keep in mind that we cannot control what happens in other countries.</p>
<p>"Moreover, there are important questions about cost and access.”</p>
</blockquote>
<h2>4. Babies born with edited genomes</h2>
<p>Most of the world reacted with shock in 2018 when a Chinese researcher announced he’d <a href="https://theconversation.com/how-a-scientist-says-he-made-a-gene-edited-baby-and-what-health-worries-may-ensue-107764">edited the germline cells of embryos</a> that went on to become twin baby girls. His stated goal was to protect them from HIV infection.</p>
<p>This development seemed to many researchers to be in violation of at least the spirit of the 2017 guidelines around human gene editing. Biomedical ethicist <a href="https://scholar.google.com/citations?user=yebS-LIAAAAJ&hl=en&oi=ao">G. Owen Schaefer</a> described the central objection: that the procedure was simply too risky, with the potential for unexpected and harmful health effects later in the girls’ lives outweighing any benefit.</p>
<p>He wrote that the “CRISPR babies” are “part of a disturbing pattern in reproduction: <a href="https://theconversation.com/rogue-science-strikes-again-the-case-of-the-first-gene-edited-babies-107684">rogue scientists bucking international norms</a> to engage in ethically and scientifically dubious reproductive research.”</p>
<h2>5. Rules and regs don’t guarantee ethical work</h2>
<p>Whatever the outcome of the current meeting, there may be a distinction between sticking to the rules and doing what’s right. Arizona State professor of life sciences <a href="https://theconversation.com/profiles/j-benjamin-hurlbut-608394">J. Benjamin Hurlbut</a> and applied ethicist <a href="https://scholar.google.com/citations?user=hOM4hNIAAAAJ&hl=en&oi=ao">Jason Scott Robert</a> underscored this point after Chinese scientist He Jiankui claimed he checked off the boxes laid out by the 2017 guidelines.</p>
<blockquote>
<p>“Public debate about the experiment should not make the mistake of <a href="https://theconversation.com/crispr-babies-raise-an-uncomfortable-reality-abiding-by-scientific-standards-doesnt-guarantee-ethical-research-108008">equating ethical oversight with ethical acceptability</a>. Research that follows the rules is not necessarily good by definition.”</p>
</blockquote>
<p>Guidelines and expectations can help define what the scientific community finds acceptable. But complying with the routines of oversight doesn’t guarantee a project is ethical. That’s a much more complicated question.</p>
<p><em>Editor’s note: This story is a roundup of articles from The Conversation’s archives.</em></p><img src="https://counter.theconversation.com/content/121912/count.gif" alt="The Conversation" width="1" height="1" />
CRISPR technology could have momentous effects if it’s used to edit genes that will be inherited by future generations. Researchers and ethicists continue to weigh appropriate guidelines.Maggie Villiger, Senior Science + Technology EditorLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1183922019-06-12T11:32:15Z2019-06-12T11:32:15ZWhat the ban on gene-edited babies means for family planning<figure><img src="https://images.theconversation.com/files/278519/original/file-20190607-52739-l05xdd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">When it comes to reproduction, couple have more choices than ever before.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/patient-couple-consulting-doctor-psychologist-on-1193897125">Chinnapong/Shutterstock.com</a></span></figcaption></figure><p>Technology surrounding the human embryo has moved out of the realm of science fiction and into the reality of difficult decisions. Clinical embryologists fertilize human eggs for the purpose of helping couples conceive. The genetic makeup of these embryos are tested on a routine basis. And today, we no longer ask “can we,” but rather, “should we” edit human embryos with the goal of implantation and delivery of a baby?</p>
<p>As a reproductive endocrinologist, I frequently encounter couples grappling with complicated reproductive issues. If one or both parents are affected by single gene disorders, these couples have the opportunity to first test their embryos and then decide whether to transfer an embryo carrying a mutation rather than finding out the genetic risk of their baby while pregnant. In some cases they may decide not to transfer an embryo that carries the mutation as part of the in vitro fertilization procedure. </p>
<p>These issues seem simple, but carry large consequences for patients. “Should we transfer an embryo affected with our genetic disorder?” “What should we do with our affected embryos if we do not transfer them?” Some patients will opt to skip testing altogether. </p>
<h2>Clinical trials of GM embryos banned in the US</h2>
<p>House Democrats this year considered, then backed away from, lifting a ban written into the budget of the U.S. Food and Drug Administration that bars the approval of any clinical trial or research “in which a <a href="https://www.sciencemag.org/news/2019/06/update-house-spending-panel-restores-us-ban-gene-edited-babies">human embryo is intentionally created or modified</a> to include a heritable genetic modification.” The current gene-editing ban prohibits editing the genes inside the cell’s nucleus, as Chinese scientist He Jiankui did. He used the gene-editing tool CRISPR to <a href="https://theconversation.com/how-a-scientist-says-he-made-a-gene-edited-baby-and-what-health-worries-may-ensue-107764">modify the CCR5 gene in twin girls</a> to give them immunity from HIV. </p>
<p>The current ban also prohibits so-called mitochondrial replacement therapy, or <a href="https://theconversation.com/how-can-a-baby-have-3-parents-97991">three-parent babies</a>. </p>
<p>Mitochondria replacement therapy, in which mitochondria carrying defective genes are replaced by healthy mitochondria from a third party <a href="https://annualmeeting.acog.org/news/many-concerns-surround-mitochondrial-transfer/">is more palatable to some</a> as mitochondrial DNA only carries a handful of genes that provide cellular energy production. </p>
<p>These scenarios of a <a href="https://theconversation.com/how-can-a-baby-have-3-parents-97991">three-parent baby</a> involve transfer of the nucleus - containing the 23 chromosomes - from the egg of the mother with the defective mitochondria into an egg from which the nucleus has been removed but the healthy mitochondria remain. The actual genetic material is changed because there is DNA from two women. However, the DNA has not been cut, pasted or otherwise modified. Although testing the safety of three-parent babies will be allowed in some countries such as the United Kingdom, the U.S. ban includes this procedure. </p>
<h2>What is germline editing?</h2>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/278558/original/file-20190607-52739-1emrruf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/278558/original/file-20190607-52739-1emrruf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/278558/original/file-20190607-52739-1emrruf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=597&fit=crop&dpr=1 600w, https://images.theconversation.com/files/278558/original/file-20190607-52739-1emrruf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=597&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/278558/original/file-20190607-52739-1emrruf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=597&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/278558/original/file-20190607-52739-1emrruf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=751&fit=crop&dpr=1 754w, https://images.theconversation.com/files/278558/original/file-20190607-52739-1emrruf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=751&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/278558/original/file-20190607-52739-1emrruf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=751&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 23 pairs of chromosomes, which are made from DNA, are stored in the nucleus of the cell. The mitochondria produce the energy for the cell and have their own DNA.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/structure-human-cells-organelles-core-nucleus-553881673?src=V9eJQZhCqeVykM3dWjPxQQ-1-37">Timonina/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>At the heart of the issue is making genetic changes to cells that could be passed on to the next generation. These are called germline cells, and changing them is called germline editing. This brings these questions to the next level, with little information to support these heartwrenching choices. </p>
<p>Germline editing can happen at different phases of fertilization. If we change the genetic makeup of a human egg or sperm, fertilize it, and transfer the resulting embryo into the womb, the result is a heritable genetic modification. Similarly, genetic changes to the embryo itself within the first few days after fertilization will be inherited by the embryo’s offspring. Both of these actions are currently banned.</p>
<h2>Is there any DNA that is OK to edit?</h2>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/278946/original/file-20190611-32351-imijs0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/278946/original/file-20190611-32351-imijs0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/278946/original/file-20190611-32351-imijs0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/278946/original/file-20190611-32351-imijs0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/278946/original/file-20190611-32351-imijs0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/278946/original/file-20190611-32351-imijs0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/278946/original/file-20190611-32351-imijs0.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">Sometimes the DNA inside the mitochondria carry mutations that cause disease. In mitochondria replacement therapy, the unhealthy mitochondria are replaced with those from a third party, or ‘parent.’</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/education-chart-biology-mitochondria-diagram-vector-1057812953?src=UHmWJcbvLQ-2FRN73FWNEQ-1-46">Vecton/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>Our genetic material is made up of DNA. This DNA is found in two locations within our cells – the nucleus and mitochondria. The DNA, which makes up our 23 pairs of chromosomes, is found inside the nucleus of every cell is a combination of the DNA from the biological mother’s egg and biological father’s sperm. Genes composed from this nuclear DNA provide the basis of most of our biologic functions and appearance including our height, eye color and our overall predisposition to diseases such as diabetes, heart disease and cancer. These traits are often the <a href="https://ghr.nlm.nih.gov/primer/basics/gene">product of multiple genes</a> working in tandem. The products of these genes work together throughout our lives, which makes the impact of editing at the embryonic level impossible to predict. </p>
<p>He Jiankui performed gene editing on nuclear DNA. This action provoked calls for <a href="https://www.asrm.org/news-and-publications/news-and-research/press-releases-and-bulletins/asrm-statement-on-reports-of-human-reproductive-gene-editing-in-china/">regulatory oversight of gene-editing techniques</a>. The concern lies in the long-term effects. In addition to their constant interaction, most of genes in the cell’s nucleus serve multiple functions. “Fixing” one aspect of a gene’s function may therefore result in <a href="https://www.bbc.com/news/health-48496652">unintended consequences</a>. </p>
<p>Those diseases <a href="https://www.ncbi.nlm.nih.gov/books/NBK132154/">caused by a single gene mutation</a> in nuclear DNA are more obvious candidates for gene editing because they are more likely to result in a cure. These include cystic fibrosis, muscular dystrophy and sickle cell anemia. </p>
<h2>Are three-parent babies different?</h2>
<p>Mitochondrial DNA is located outside the cell’s nucleus and passed down directly from the female egg to the embryo. Genes composed of mitochondria DNA enable mitochondria to produce energy for the whole cell. <a href="https://ghr.nlm.nih.gov/mitochondrial-dna">Mutations in mitochondrial genes</a> have been associated with <a href="http://doi.org/10.1038/nrdp.2016.80">severe disorders</a> such as <a href="https://ghr.nlm.nih.gov/condition/leigh-syndrome">Leigh syndrome</a> and <a href="https://ghr.nlm.nih.gov/condition/mitochondrial-complex-iii-deficiency">mitochondrial complex III deficiency</a> that can affect the brain, kidney and heart.</p>
<p>Just as nuclear DNA modification may remove the risk for single gene disorders, mitochondria replacement therapy would replace these mutated mitochondrial genes with mitochondria from a donor egg – a change that will passed to future generations.</p>
<p>Throughout this discussion, I try to maintain a sense of empathy for those families for whom this could be their only hope of having a healthy biologically related child. I also try to convey that we are at the beginning of a long road that will require a thoughtful approach to anything we do. The technology is here, but we know so much less about its effects than we should. </p>
<p>These editing therapies will permanently change all the descendants of a couple. In some cases it could rid a family of a genetic disease. In others, the unintended effects may be worse than the disease itself. This is the purpose of ethically appropriate research with careful oversight. The ban does not change the need for discussion. If anything, it brings the debate back to the reality of patients seeking care for diseases that currently have no cure.</p>
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<p class="fine-print"><em><span>Marie Menke 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>A ban on clinical trials involving gene editing rules out the controversial procedure done in China. But it also prevents procedures that could offer couples a chance for healthy children without genetic disorders.Marie Menke, Assistant Professor of Obstetrics, Gynecology & Reproductive Sciences, University of PittsburghLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1170702019-05-29T12:34:36Z2019-05-29T12:34:36ZGene-edited babies don’t grow in test tubes – mothers’ roles shouldn’t be erased<figure><img src="https://images.theconversation.com/files/276835/original/file-20190528-42580-eeaqjv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">He Jiankui claims he helped make the world's first genetically edited babies: twin girls whose DNA he said he altered. </span> <span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Genetic-Frontiers-Gene-Edited-Babies/95551dbf28c24ab086bd60d11c1bcf6b/31/0">AP Photo/Mark Schiefelbein</a></span></figcaption></figure><p><a href="https://www.newscientist.com/article/mg24032073-600-gene-editing-is-so-easy-to-do-that-we-couldnt-stop-it-if-we-wanted-to/">A baby with incandescent green eyes</a>, <a href="https://geneticliteracyproject.org/2018/11/26/crispr-uproar-chinese-researcher-claims-first-gene-edited-babies/">a baby stamped with a bar code</a>, <a href="https://www.technologyreview.com/s/612997/the-crispr-twins-had-their-brains-altered/">another with a glowing gold brain</a>: these are some of the images illustrating stories about the gene-edited twin girls born last November after the world learned of Chinese scientist He Jiankui’s <a href="https://theconversation.com/how-a-scientist-says-he-made-a-gene-edited-baby-and-what-health-worries-may-ensue-107764">controversial efforts to modify embryos</a> with the CRISPR-Cas9 genome editing tool. </p>
<p>The sensational revelation, <a href="https://theconversation.com/the-road-to-enhancement-via-human-gene-editing-is-paved-with-good-intentions-107677">questionable ethics</a> and powerful new technologies of gene editing have made He’s research the subject of ongoing fascination and debate. But strikingly absent in the news has been any discussion of where the embryos developed, how the babies came into the world and who will care for them.</p>
<p>That is to say, their mother. </p>
<p>She is nowhere to be seen in any illustration of the “CRISPR babies,” and news coverage mentions her only in passing. Dubbed the “Chinese Frankenstein,” it is as if the rogue male scientist is the twins’ sole creator.</p>
<p><a href="http://racheladams.net">I am a humanities professor</a> who teaches bioethics, disability and culture, and I find discussion with my students increasingly focused on the implications of rapidly unfolding genetic science. I am also the mother of a child with a genetic disability who reminds me, on a daily basis, that genes are only supporting actors in the complex and wonderful drama of my son’s personhood, and an even more minor backdrop to the ongoing labor of parenting. This means that I have a personal, as well as professional, stake in how genetic knowledge is explained and debated in public.</p>
<p>Ignoring the twins’ mother matters for reasons beyond this individual story. </p>
<p>First, it perpetuates a misunderstanding of science. CRISPR-Cas 9 is a revolutionary technology that allows for quick and precise gene editing, with promising applications in agriculture, pest control and biomedicine. But it also has weighty implications because it can introduce heritable, and potentially irreversible, changes in subsequent generations.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/276831/original/file-20190528-42565-1nl72ou.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/276831/original/file-20190528-42565-1nl72ou.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/276831/original/file-20190528-42565-1nl72ou.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/276831/original/file-20190528-42565-1nl72ou.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/276831/original/file-20190528-42565-1nl72ou.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/276831/original/file-20190528-42565-1nl72ou.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/276831/original/file-20190528-42565-1nl72ou.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/276831/original/file-20190528-42565-1nl72ou.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>
<figcaption>
<span class="caption">Zhou Xiaoqin, left, and Qin Jinzhou, an embryologist, part of the team working with scientist He Jiankui, view a time lapse image of embryos on a computer screen at a lab in Shenzhen in southern China’s Guandong province.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/China-Gene-Edited-Babies/a1b252903c424acf9609c03467a2fa6e/39/0">AP Photo/Mark Schiefelbein</a></span>
</figcaption>
</figure>
<h2>The myth of the test tube babies</h2>
<p>Of course, there are good reasons to conceal the mother’s identity. He claimed his study was for HIV research and prevention and recruited couples with an HIV-positive male partner and an uninfected female. Such couples were promised fertility treatments in exchange for their participation. Intense stigmas around both HIV and infertility in China are good reason to shroud both parents in secrecy. </p>
<p>Another is the controversial nature of He’s research and the deliberately spectacular way he chose to reveal it. Obscuring the mother’s identity protects her privacy, shielding her family from unwanted and largely negative publicity raging around the experiment. But there is a difference between protecting a person’s identity and obscuring her story. What does the virtual invisibility of a maternal presence say about the twins’ conception, birth and future well-being? </p>
<p>As in Mary Shelley’s “Frankenstein” and any number of later science fiction narratives, it is as if the babies were not only conceived but developed in a laboratory. It is as if the actual woman whose uterus nurtured their bodies, whose flesh was cut open and sutured to ensure their safe delivery (assuming they were born by C-section, as are many twins), whose breasts are making milk to nourish them, didn’t exist at all. As if, like Shelley’s misguided doctor, He is the babies’ sole creator.</p>
<p>In fact, now that the babies are born, their mother is surely their primary caregiver. Regardless of how her twins were conceived, she is responsible for their well-being and development. Like other new mothers, she has doubtless experienced wakeful nights, breasts leaking milk, countless dirty diapers. By now she has probably seen her babies smile, roll over, babble and play with toys. But these more pedestrian experiences of motherhood must also be intermingled with constant media, scientific and governmental scrutiny of her children and the processes that brought them into being. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/276837/original/file-20190528-42584-1w7yrla.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/276837/original/file-20190528-42584-1w7yrla.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/276837/original/file-20190528-42584-1w7yrla.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/276837/original/file-20190528-42584-1w7yrla.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/276837/original/file-20190528-42584-1w7yrla.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/276837/original/file-20190528-42584-1w7yrla.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/276837/original/file-20190528-42584-1w7yrla.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/276837/original/file-20190528-42584-1w7yrla.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>
<figcaption>
<span class="caption">A depiction of Dr. Frankenstein and his creation in a wax museum in Barcelona.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/barcelona-spain-aug-11-2018-doctor-1159963069?src=oI_hAudiDrfBUnqUx0GmjA-1-51">Anton_Ivanov</a></span>
</figcaption>
</figure>
<h2>The hidden labor of care</h2>
<p>The twins’ mother must be aware her babies face uncertain health outcomes as a result of their edited genes. He claimed he was trying to protect the girls from HIV. By <a href="http://doi.org/10.1038/d41586-018-07573-w">all accounts</a>, the couple was misled about the nature of He’s research, meaning that they could not have given fully informed consent. </p>
<p>As part of the consent agreement, He’s team had promised to oversee the twins’ medical needs until age 18. But now that the scientist has <a href="http://time.com/5469111/he-jiankui-scientist-missing-gene-edited-babies/">disappeared</a> and his <a href="https://www.apnews.com/0be63430c5914f09a124b968c844d994">lab disbanded</a>, it is unclear who will provide them with health care. </p>
<p>CRISPR does not bypass the role of mothers in species reproduction and care. He is a Dr. Frankenstein in the recklessness of his methods, but not because he has managed to supersede the biological functions of the female body or the contribution of mothers (biological or not) to a child’s development. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/276848/original/file-20190528-42580-1d5kgwx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/276848/original/file-20190528-42580-1d5kgwx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/276848/original/file-20190528-42580-1d5kgwx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/276848/original/file-20190528-42580-1d5kgwx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/276848/original/file-20190528-42580-1d5kgwx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/276848/original/file-20190528-42580-1d5kgwx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/276848/original/file-20190528-42580-1d5kgwx.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">No genetic technology eliminates the mother’s role.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/portrait-woman-relaxing-home-her-little-512079628?src=TtMKlfeLNhjlohddWKwrjA-1-29">pixelheadphoto digitalskillet/Shutterstock.com</a></span>
</figcaption>
</figure>
<h2>The politics of maternal invisibility</h2>
<p>Like other new reproductive technologies, from ultrasound to amniocentesis and IVF, CRISPR is likely to present pregnant women with more responsibilities and decisions, not remove them from the process. At a time when leading scientists and bioethicists are calling for widespread and informed civic debate about the future of genomic research, it is essential to foster, rather than obscure, public understanding of basic genetic science.</p>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/276841/original/file-20190528-42588-1xojlpf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/276841/original/file-20190528-42588-1xojlpf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/276841/original/file-20190528-42588-1xojlpf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=652&fit=crop&dpr=1 600w, https://images.theconversation.com/files/276841/original/file-20190528-42588-1xojlpf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=652&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/276841/original/file-20190528-42588-1xojlpf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=652&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/276841/original/file-20190528-42588-1xojlpf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=820&fit=crop&dpr=1 754w, https://images.theconversation.com/files/276841/original/file-20190528-42588-1xojlpf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=820&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/276841/original/file-20190528-42588-1xojlpf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=820&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Excluding the mother from talk about gene editing created the impression that the mother is now obsolete.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/genetic-engineering-vitro-fertilization-eps-8-1230974200?src=ENuyRzFDhQbVzA4lEBm-Yg-1-13">Aleutie</a></span>
</figcaption>
</figure>
<p>The invisibility of the mother’s body in images of the CRISPR babies also makes a political statement. The picture of a <a href="https://www.telegraph.co.uk/family/parenting/designer-babies-far-should-science-go-create-perfect-human/">fetus growing</a> <a href="https://theconversation.com/those-designer-babies-everyone-is-freaking-out-about-its-not-likely-to-happen-103079">in a test tube</a> or a free-floating womb is not just the stuff of science fiction, but has also been widely used in anti-abortion arguments. By representing the fetus as if it were a baby capable of independent life, opponents of reproductive freedom have claimed it has rights that take priority over those of the woman who sustains it. This is the logic at work behind <a href="https://www.nytimes.com/aponline/2019/05/20/us/ap-us-abortion-alabama.html?searchResultPosition=10">recent laws passed in Alabama</a> and other states that restrict abortion once a fetal heartbeat is detected, even if the pregnancy resulted from rape or incest. Regardless of He’s own politics, representations of the CRISPR babies contribute to deprioritizing maternal health and autonomy, as well as the ongoing work of mothering.</p>
<p>CRISPR is a revolutionary technology whose applications should be thoroughly debated by stakeholders at all levels of society. But nowhere does the new science propose to replace the female body or the role of mothers in a child’s care and well-being. It is time to edit the stories we tell about gene editing. We can preserve the privacy of the mother of Lulu and Nana while also acknowledging her place in any consideration of their future, and the future life of the species.</p><img src="https://counter.theconversation.com/content/117070/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Rachel Adams 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>News of the gene-edited babies excludes images of the children’s mother. Cutting her out of the picture underscores the idea that the mother is obsolete and babies can be created in the lab.Rachel Adams, Professor of English and Comparative Literature, Columbia UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1121072019-03-06T15:00:04Z2019-03-06T15:00:04ZMystery of French babies born with deformed arms – here’s what a developmental biologist thinks<figure><img src="https://images.theconversation.com/files/262400/original/file-20190306-100772-xxb1sf.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/download/confirm/403103896?size=medium_jpg">bogonet/Shutterstock</a></span></figcaption></figure><p>REMERA, a French national birth-defect registry, recently identified clusters of children born with malformed limbs in three rural regions in <a href="https://www.thelocal.fr/20181031/11-more-cases-of-babies-born-with-missing-arms-in-france">France</a>. Each cluster has three to eight children with malformations that include children with missing or deformed arms and hands.</p>
<p>The French public health department (Santé Publique France) originally suggested that these cases were not above what was naturally expected each <a href="https://www.theguardian.com/world/2018/oct/08/france-doctors-fail-solve-mystery-babies-missing-limbs">year</a>. Around 3-4% of children, worldwide, have a <a href="https://genetics.emory.edu/documents/resources/Emory_Human_Genetics_General_Population_Risk_for_Birth_Defects.PDF">birth malformation</a>. Although genetic, chromosomal and environmental causes – such as medicines – can account for some of these malformations, in most cases the cause is unknown.</p>
<p>It is difficult to know if the type and number of these limb differences in France are to be expected or if they are cause for concern. This is made more difficult by the fact that the French birth-defects registry only covers <a href="https://med.news.am/eng/news/21245/parents-demand-answers-after-mysterious-birth-defect-leaves-more-than-20-french-babies-without-arms.html">19% of the country’s births</a>. </p>
<p>However, Santé Publique France has now established a <a href="https://www.france24.com/en/20190221-france-baby-babies-born-arm-upper-limb-reduction-defect-remera-spf">formal panel</a> to investigate these cases and determine the cause, probably in response to <a href="https://med.news.am/eng/news/21245/parents-demand-answers-after-mysterious-birth-defect-leaves-more-than-20-french-babies-without-arms.html">pressure</a> from the public to find answers.</p>
<h2>Looking for causes</h2>
<p>Exactly how limb defects come about is still not fully understood, but we do know they are linked to exposure to certain drugs, such as <a href="https://theconversation.com/thalidomide-the-drug-with-a-dark-side-but-an-enigmatic-future-50330">thalidomide</a>, as well as <a href="https://www.cdc.gov/ncbddd/birthdefects/ul-limbreductiondefects.html">industrial pollutants</a> – as was the case in <a href="http://news.bbc.co.uk/1/hi/england/northamptonshire/8624828.stm">Corby</a>, England in the 1990s.</p>
<p>Genetic influences are a potential cause, though this appears to have been ruled out by <a href="https://www.thelocal.fr/20181031/the-story-behind-the-high-number-of-babies-in-france-born-without-arms">REMERA</a> as the children’s families did not have similar problems in previous generations. </p>
<p>Of course, spontaneous mutations in genes involved in limb formation could be the cause, but these events are rare. The fact that it occurred in several children causing similar damage in three different rural areas of France makes this theory unlikely.</p>
<p>REMERA has proposed that the limb malformations could result from exposure to environmental pollutants and toxins, which could include <a href="https://www.thelocal.fr/20181031/the-story-behind-the-high-number-of-babies-in-france-born-without-arms">pesticides and herbicides</a> that are used on nearby <a href="https://www.sott.net/article/399595-Pesticides-France-launches-another-probe-after-more-birth-defects-cases-revealed">farms</a>. This may be a credible theory as herbicides, such as <a href="https://www.ncbi.nlm.nih.gov/pubmed/20695457">glyphosate</a>, have been shown to cause limb malformations in frog embryos in laboratory experiments.</p>
<p>Also, insecticides, such as methoprene, that have contaminated ponds in the wild have been <a href="https://www.ncbi.nlm.nih.gov/pubmed/12763670">linked</a> to malformed limbs in wild frogs in the US and Canada. </p>
<p>Laboratory tests show that these compounds can convert into a <a href="https://www.ncbi.nlm.nih.gov/pubmed/20695457">retinoic-acid-like molecule</a>. Retinoic acid comes from vitamin A and is very important in embryonic development. Exposing mink frog embryos to retinoic acid in lab tests resulted in a <a href="https://www.ncbi.nlm.nih.gov/pubmed/10404649">range of damage</a> to the embryos. </p>
<p>These facts suggest that agricultural chemicals, getting into the water supply or food chain, could influence embryonic development and result in damage. But more work is needed before we can be sure that these chemicals cause limb malformations in humans.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/262405/original/file-20190306-100775-13vvsqc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/262405/original/file-20190306-100775-13vvsqc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=397&fit=crop&dpr=1 600w, https://images.theconversation.com/files/262405/original/file-20190306-100775-13vvsqc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=397&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/262405/original/file-20190306-100775-13vvsqc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=397&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/262405/original/file-20190306-100775-13vvsqc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=499&fit=crop&dpr=1 754w, https://images.theconversation.com/files/262405/original/file-20190306-100775-13vvsqc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=499&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/262405/original/file-20190306-100775-13vvsqc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=499&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Could agricultural chemicals be to blame?</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/348615704?size=medium_jpg">Fotokostic/Shutterstock</a></span>
</figcaption>
</figure>
<h2>Unilateral limb defect</h2>
<p>Perhaps what is most striking about the reported French cases is that many of the children have <a href="https://www.cdc.gov/ncbddd/birthdefects/ul-limbreductiondefects.html">defects</a> to just one arm. This is called a unilateral limb defect. How unilateral limb differences come about is poorly understood.</p>
<p>Recent research shows that the right and left arms may have differences in some of the genes involved in ensuring the arms form correctly and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215935/">symmetrically</a>. We also know that retinoic acid can control some of the genes involved in <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215935/">forming limbs</a>.</p>
<p>The effect of insecticides, pesticides and herbicides on human health is also poorly understood. We know some can cause cancer – though how they do this is unclear. Given that some herbicides and insecticides appear to be able to affect retinoic acid signalling, which is needed to control gene activity in the embryo, it might help explain the unilateral limb differences.</p>
<p>It cannot be ruled out these clusters could simply be random events and within the range of what is to be expected naturally. However, this seems difficult to confirm with incomplete birth-defect records. Given the reported use of pesticides and herbicides in the cluster areas, all lines of investigation should be kept open.</p><img src="https://counter.theconversation.com/content/112107/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Neil Vargesson would like to thank Emmanuelle Amar, Elisabeth Gnasia and members of REMERA for helpful discussions and information sharing regarding the clusters of children in France.
Neil Vargesson has received no funding for this article.</span></em></p>Possible causes of limb malformations in babies born in rural areas of France.Neil Vargesson, Professor in Developmental Biology, University of AberdeenLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1116032019-02-26T05:40:38Z2019-02-26T05:40:38ZWhy your face looks the way it does<figure><img src="https://images.theconversation.com/files/260878/original/file-20190225-26165-1scd4o5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Faces form during the very early stages of embryology. </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/two-little-sisters-on-beach-1173947296?src=KxVntPCn7H_RlhXfwPdEYA-1-78">from www.shutterstock.com</a></span></figcaption></figure><p>Is your face long? Wide? Big nose? Small ears? High forehead? </p>
<p>It’s our faces that characterise how the world sees us, and how we recognise our close friends and family. If you’re lucky enough to be born with a highly symmetrical or a very unique face, perhaps you might have a career as a model or actor. </p>
<p>But how do our faces come about – and what happens when things go awry? We need to look way back to the early stages of life to find out.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/what-makes-you-a-man-or-a-woman-geneticist-jenny-graves-explains-102983">What makes you a man or a woman? Geneticist Jenny Graves explains</a>
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</em>
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<h2>From a fertilised cell</h2>
<p>Like humans, most creatures throughout the animal kingdom have an instantly recognisable face. Such distinctive features as the trunk of an elephant, the long jaws and abundant sharp teeth of a crocodile, varied shapes and sizes of bird beaks and the unique bill of the platypus are all distinct and recognisable. </p>
<p>Our faces arise during the earliest stages of life. And quite incredibly, the processes that give rise to all these distinctive faces – animal and human – are exceptionally well conserved (that is, haven’t changed much over the course of evolutionary history). Amongst humans and other creatures with backbones (together known as vertebrates), the genes and biological processes that make a face are really very similar.</p>
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<p>
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<strong>
Read more:
<a href="https://theconversation.com/considering-using-ivf-to-have-a-baby-heres-what-you-need-to-know-108910">Considering using IVF to have a baby? Here's what you need to know</a>
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<p>All animals and humans start out as a fertilised cell. Through thousands of cell divisions, the tissues that will eventually make up the skull, jaws, skin, nerve cells, muscles and blood vessels form and come together to create our face. These are the craniofacial tissues. </p>
<p>The face is among the earliest recognisable features that form in an embryo, with the future eye, nose, ear and tissues that will eventually form the upper and lower jaws all established by about <a href="https://embryology.med.unsw.edu.au/embryology/index.php/Palate_Development">7-8 weeks in human gestation</a>. </p>
<h2>Fusion of two sides</h2>
<p>By the sixth week of human development, the major fusion processes of the face have taken place – the two sides of the developing nose will join, both to each other and to the tissue that will become the upper lip. This first fusion (the formation of the “primary palate”) establishes the correct anatomy of the face, and serves as a structural guide for the next major fusion event – that of the secondary, or hard palate. </p>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/260090/original/file-20190221-148536-1nwah0u.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/260090/original/file-20190221-148536-1nwah0u.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/260090/original/file-20190221-148536-1nwah0u.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=798&fit=crop&dpr=1 600w, https://images.theconversation.com/files/260090/original/file-20190221-148536-1nwah0u.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=798&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/260090/original/file-20190221-148536-1nwah0u.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=798&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/260090/original/file-20190221-148536-1nwah0u.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1003&fit=crop&dpr=1 754w, https://images.theconversation.com/files/260090/original/file-20190221-148536-1nwah0u.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1003&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/260090/original/file-20190221-148536-1nwah0u.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1003&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 formation of the face – tissues that comprise the future nose and upper lip (red), the sides of the nose (blue) and the upper and lower jaws (green) arise by the 4th week of development (A) and have migrated and fused to form a distinctive ‘face’ by the 8th week of development (D).</span>
<span class="attribution"><a class="source" href="http://dev.biologists.org/content/132/5/851">New insights into craniofacial morphogenesis</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>The hard palate originates as two separate “shelves”, one from the left side of the embryo and one from the right. These shelves elevate and grow together to form one continuous structure, ultimately separating the cavities of the nose and sinuses from that of the mouth. (You can feel this hard palate with your tongue – it’s the roof of your mouth.) </p>
<p>Once these fusion processes are complete (by about week 9 of gestation, still well inside the first trimester), the cells of the face still continue to dynamically move, reshape, and take on functional roles. This includes forming the structural framework of the bones, the delivery of oxygen and nutrients by the blood vessels, and controlling eye and jaw movements by the facial muscles. </p>
<h2>Sometimes things go astray</h2>
<p>Of course, given the incredible complexity and synchronicity required for all these cells and tissues to end up in the correct space, it is perhaps very surprising that things do not go wrong in craniofacial development more often than they do. </p>
<p>Across the world, <a href="https://www.marchofdimes.org/mission/march-of-dimes-global-report-on-birth-defects.aspx">4-8% of all babies</a> are born each year with defects affecting one or more organs. Of these children, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039913/">75% show some anomaly of the head or face</a>. </p>
<p>Problems can occur with any cell types that make up the skull, face, blood vessels, muscles, jaws and teeth. </p>
<p>But one of the most common craniofacial defects are palatal clefts, where the hard palate does not fuse correctly, leaving children (roughly 1 in 700 worldwide) with a large gap between their nasal passages and mouth. </p>
<p>Although relatively easily corrected by trained reconstructive surgeons in first-world health care systems, significant ongoing healthcare is still essential. </p>
<p>Services such as speech pathology and psychological counselling are often required. The children also may need medical attention to improve hearing, as problems with middle ear bones often come with other craniofacial defects.</p>
<p>Later surgeries to correct muscular defects do not come cheaply – assuming of course that such surgical and allied health is available to the individual in the first place. This is frequently not the case outside the first world.</p>
<h2>Understanding why problems occur</h2>
<p>To reduce both the severity and incidence of craniofacial defects, researchers use animal model systems – particularly mouse, chicken, frog and zebrafish embryos – to try and uncover the reasons why these defects occur. </p>
<p>Of all craniofacial defects, 25% are attributed (at least partially) to environmental factors such as smoking, heavy alcohol or drug use, toxic metals and maternal infection (such as salmonella or rubella) during <a href="https://www.marchofdimes.org/mission/march-of-dimes-global-report-on-birth-defects.aspx">pregnancy</a>.</p>
<p>About 75% of all craniofacial defects are linked to genetic factors. As most of the genes that control craniofacial development in animals also do so in humans, using these animal models helps us better understand human palate development and how specific genes are involved. </p>
<p>Eventually this work may lead to new prevention and treatment strategies, for example supplementing the mother’s diet with beneficial nutrients and vitamins. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/better-health-and-diet-well-before-conception-results-in-healthier-pregnancies-94400">Better health and diet well before conception results in healthier pregnancies</a>
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</em>
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<p>An example of such an intervention is the B-vitamin folate, used to reduce neural tube defects such as spina bifida. Mandatory folic acid fortification of food in the USA in 1999-2000 resulted in a 25-30% reduction in severe neural tube defects, clearly an exceptional outcome for <a href="https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5317a3.htm">newborns and their families</a>.</p>
<p>Through greater understanding of the genetic processes that drive facial growth, further beneficial factors will be identified that can be safely given to pregnant mothers, and give a far better start to life to children that may otherwise be born with a craniofacial disorder.</p><img src="https://counter.theconversation.com/content/111603/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sebastian Dworkin has previously received funding from the Australian Research Council (ARC) and National Health and Medical Research Council (NHMRC) to conduct research into the genes that regulate embryonic development, particularly those that regulate formation of the facial skeleton. </span></em></p>Problems in facial development can occur with the skull, face, blood vessels, muscles, jaws and teeth. But it’s the hard palate forming the roof of your mouth that’s most commonly affected.Sebastian Dworkin, Group Leader, Developmental Genetics Lab, La Trobe UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1010222018-08-08T20:49:39Z2018-08-08T20:49:39ZWho gets the frozen embryos in the divorce?<figure><img src="https://images.theconversation.com/files/231163/original/file-20180808-142251-18mjuk9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">An embryologist pulls out frozen embryos and egg cells.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>In a <a href="https://www.canlii.org/en/on/onsc/doc/2018/2018onsc4506/2018onsc4506.html">recent judgment in Ontario, Canada</a>, a court has determined that <a href="https://www.ctvnews.ca/health/disputed-frozen-embryo-awarded-to-ex-wife-contract-law-applies-judge-rules-1.4036714">embryos can be understood as “property”</a> and decisions about them made accordingly. </p>
<p>This <a href="https://www.canadianlawyermag.com/legalfeeds/author/gabrielle-giroday/judge-says-sudbury-woman-can-use-embryo-after-legal-fight-with-ex-husband-16035/">raises new concerns</a> about decision-making related to reproductive tissues, namely that embryos may be treated like other forms of contested marital property.</p>
<p>In the case in question (S.H. v. D.H.), a woman wanted to use a frozen embryo that she and her ex-husband created in 2012. A single embryo remained after the woman had conceived using in vitro fertilization and given birth to a son in 2012. It was subsequently frozen and put into storage. </p>
<p>When the couple created the embryo, they signed a consent form stating that in case of divorce, it would be used as per the woman’s (patient’s) wishes. </p>
<p>The court found that, following the contract put in place by the consent form, the embryo is property that the woman can use for her own reproductive purposes.</p>
<h2>A failure on two accounts</h2>
<p>There are <a href="http://www.thecourt.ca/human-sperm-to-constitute-legal-property-lam-v-university-of-british-columbia/">several cases in Canada</a> in which reproductive tissue has been found to constitute property, and one case <a href="https://www.canlii.org/en/bc/bcsc/doc/2012/2012bcsc584/2012bcsc584.html">J.C.M. v. A.N.A</a> in which frozen sperm could be divided like other marital assets. And, in 2005, a court in Alberta ruled in the case of C.C. v. A.W. — in which a man provided sperm to a friend so that she could create embryos using in vitro fertilization. After the birth of twins, the woman froze the four remaining embryos for her potential future use. Although the man did not consent to the use of the remaining embryos, the court ruled that they belonged to the woman as they were property, <a href="https://blog.oup.com/2015/06/reproductive-material-disputes/">“chattels that can be used as she sees fit.”</a></p>
<p>Despite the similar circumstances of these cases, the decision in S.H. v. D.H. fails on two accounts. </p>
<p>First, it does not address the existence of regulations about consent for the use of embryos in Canada developed since C.C. v. A.W. These regulations allow for the withdrawal of consent of relevant parties up to the time that an embryo is used. </p>
<p>Second, it does not address the complex nature of making decisions about embryo disposition, which require consent well beyond what is decided at the time that an embryo is created.</p>
<h2>Donor can withdraw consent</h2>
<p>The regulations are relatively straightforward. Under Canada’s Assisted Human Reproduction Act, <a href="http://laws-lois.justice.gc.ca/eng/regulations/SOR-2007-137/page-1.html">there are regulations</a> about how consent for the creation and use of embryos should occur.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/231160/original/file-20180808-191031-1wbrj51.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/231160/original/file-20180808-191031-1wbrj51.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/231160/original/file-20180808-191031-1wbrj51.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/231160/original/file-20180808-191031-1wbrj51.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/231160/original/file-20180808-191031-1wbrj51.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/231160/original/file-20180808-191031-1wbrj51.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/231160/original/file-20180808-191031-1wbrj51.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">An embryologist works on an embryo in the Create Health fertility clinic in London, U.K.</span>
<span class="attribution"><span class="source">(AP Photo/ Sang Tan)</span></span>
</figcaption>
</figure>
<p>Under s.8(3) of the act, “no person shall make use of an in vitro embryo for any purpose unless the donor has given written consent, in accordance with the regulations, to its use for that purpose.” </p>
<p>And although in this case the consent forms indicate that the embryo could be used as to the woman’s wishes, <a href="https://www.canada.ca/en/health-canada/services/healthy-living/reports-publications/assisted-human-reproduction/assisted-human-reproduction-act.html#a8">the regulations state</a> that the donor of an embryo can withdraw their consent to its use, so long as they do it in writing.</p>
<p>The question, then, is whether the ex-husband constitutes a donor. He does. Under Part 3 of the regulations, the donor is the “individual or individuals for whose reproductive use an in vitro embryo is created.” This includes people who are “spouses or common-law partners at the time the in vitro embryo is created, regardless of the source of the human reproductive material used to create the embryo.” </p>
<p>In short, if — as the court suggests — embryos are property that can be allocated like other marital assets under provincial law, the woman could have the embryo. </p>
<p>But in keeping with the regulations (that are part of <a href="https://lop.parl.ca/content/lop/researchpublications/cei-13-e.htm">the criminal provisions</a>) of the Assisted Human Reproduction Act, she cannot use it for reproductive purposes without her ex-husband’s consent. </p>
<h2>The issue of ‘buyer’s remorse’</h2>
<p>Beyond the existence of the regulations, decisions about embryos — in the courts and otherwise — should not rely on fixed understandings of consent. </p>
<p><a href="https://www.ncbi.nlm.nih.gov/pubmed/26872758">Canadian research, including my own, has found that people are often confused about their options</a>. Decision-making about what to do with embryos happens at an emotionally charged time when people are inching closer toward their goal of having a child, and overwhelmed with the choices they are faced with as part of that process. </p>
<p>Further, other scholars have demonstrated that people <a href="https://academic.oup.com/humrep/article/22/12/3124/2385171">change their minds about what to do with the embryos they’ve created over time</a>, and that staged processes of consent may be necessary when it comes to frozen embryos in storage. </p>
<p>Getting consent at multiple stages is difficult — since people do not always respond to clinic requests about their embryos because they have such trouble making decision — but it is necessary. And the consent regulations of the Assisted Human Reproduction Act allow for this, in part by making explicit that consent can be withdrawn.</p>
<p>Towards the end of the judgment, Justice Del Frate writes that “one cannot apply buyer’s remorse” to the creation of an embryo. But therein lies the trouble. The research on decision making related to embryos suggests that one should be able to change their mind, and the regulations under the Assisted Human Reproduction Act outlines how they can.</p><img src="https://counter.theconversation.com/content/101022/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Alana Cattapan has received funding from the Social Sciences and Humanities Research Council of Canada, the Canadian Institutes of Health Research, and the Saskatchewan Health Research Foundation. She is on the Board of the Canadian Research Institute for the Advancement of Women.</span></em></p>A recent ruling in an Ontario court fails to consider law governing the use of embryos.Alana Cattapan, Assistant Professor, Johnson Shoyama Graduate School of Public Policy, University of SaskatchewanLicensed 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/824172017-09-04T13:50:08Z2017-09-04T13:50:08ZHow animal genes go into battle to dominate their offspring<figure><img src="https://images.theconversation.com/files/183840/original/file-20170829-6710-pwups5.png?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">She'll be more like me than you.</span> </figcaption></figure><p>The burdens of becoming parents are often shared unequally between male and female animals. This is particularly true of species that give birth to live young, where male duties such as defending the breeding territory and building dens or nests rarely compare with the ordeals of pregnancy and labour. </p>
<p>You might have thought that animals just “accept” this imbalance and get on with it. But actually, they compete over how much each parent contributes. This isn’t like the competition to win a mate, with locking horns or displays of plumage. Instead this remarkable battle takes place at the level of the genes. </p>
<p>It now appears it may have evolved very early in animal evolution, perhaps among the first child-bearing animals. What is more, it may even help to explain why animals diversified into different lineages. </p>
<h2>Creatures great and small</h2>
<p>One arena in which this battle plays out is over the size of offspring. In principle it’s in both a mother’s and father’s interests to produce bigger newborns, since they are more likely to prevail in the struggle for food and survival. </p>
<p>Yet live-bearing females are more likely to die giving birth to larger offspring or become unable to reproduce again. Their mates needn’t care – unless they are likely to sire more broods together, as with humans and certain gibbons, wolves and mice. Otherwise, the males’ only concern is that their mate invests as much as possible in the offspring they produce together. </p>
<p>This common conflict of interests <a href="https://academic.oup.com/beheco/article/14/3/301/255814/Should-young-ever-be-better-off-with-one-parent">manifests</a> itself in <a href="http://www.jstor.org/stable/3677005?seq=1#page_scan_tab_contents">various ways</a> in nature. Males often desert pregnant females – from <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2535784/">birds</a> to humans, for example – thereby leaving them with the burden of bringing up the young. More rarely, in some normally biparental species females desert males. We see this in some <a href="https://www.nature.com/articles/ncomms9449">beetles</a>, for example.</p>
<p>The genetic battle mentioned previously is another manifestation of this conflict. The males of many species <a href="https://www.ncbi.nlm.nih.gov/pubmed/1997210">can manipulate</a> the genes that they pass on to their offspring so that they induce extra growth at the expense of the mother. As with desertion, this effectively hands the female a greater share of the child-bearing burden than is in her interests. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/183842/original/file-20170829-6691-kt09h4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/183842/original/file-20170829-6691-kt09h4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/183842/original/file-20170829-6691-kt09h4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=392&fit=crop&dpr=1 600w, https://images.theconversation.com/files/183842/original/file-20170829-6691-kt09h4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=392&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/183842/original/file-20170829-6691-kt09h4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=392&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/183842/original/file-20170829-6691-kt09h4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=492&fit=crop&dpr=1 754w, https://images.theconversation.com/files/183842/original/file-20170829-6691-kt09h4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=492&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/183842/original/file-20170829-6691-kt09h4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=492&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Wallaby tonight?</span>
<span class="attribution"><a class="source" href="https://pixnio.com/fauna-animals/rats-mice-and-voles-pictures/deer-mouse-animal-peromyscus-maniculatus">Susan Freeman</a></span>
</figcaption>
</figure>
<p>It works as follows. When an embryo grows inside its mother, it consumes resources from her, signalling its metabolic needs along the way. These signals are influenced by certain hormones which either come from the growth genes of the mother or father. The males manipulate the females to deliver more resources by increasing the extent to which these hormones are produced through a chemical modification of their growth genes during sperm formation. </p>
<p>Females have evolved mechanisms to resist this. They can, for instance, pass on to their offspring what is known as a “silenced copy” of their own growth gene. This can counterbalance the male genes’ influence by making the embryo grow less than it otherwise would. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/183843/original/file-20170829-7186-ut0sza.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/183843/original/file-20170829-7186-ut0sza.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/183843/original/file-20170829-7186-ut0sza.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/183843/original/file-20170829-7186-ut0sza.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/183843/original/file-20170829-7186-ut0sza.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/183843/original/file-20170829-7186-ut0sza.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/183843/original/file-20170829-7186-ut0sza.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/183843/original/file-20170829-7186-ut0sza.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>
<figcaption>
<span class="caption">Cells dividing.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/human-animal-cells-on-colorful-background-329634500?src=PmIaXm5fWSUa9ID3Y_GSRw-1-51">Kateryna Kon</a></span>
</figcaption>
</figure>
<p>This battle is far less prevalent in truly monogamous species, including humans. This goes back to the fact that it becomes less genetically necessary where the two parents have a common interest in the female producing more offspring in future. </p>
<h2>Mouse control</h2>
<p>British microbiologist David Haig <a href="https://www.ncbi.nlm.nih.gov/pubmed/12728278">first proposed</a> in 2003 that this battle was more likely in organisms where one sex disproportionately contributes to the offspring, such as live-bearing species, particularly polygamous ones. This was used to explain the puzzling size of the offspring of crosses between oldfield mice and deer mice. </p>
<p>Separately, these species produce similar sized offspring. Yet crosses between male deer mice and female oldfield mice produce offspring that are larger, while the offspring from female deer mice and oldfield males are smaller. <a href="http://animaldiversity.org/accounts/Peromyscus_polionotus/">Oldfield mice</a> are monogamous while <a href="http://www.esf.edu/aec/adks/mammals/deer_mouse.htm">deer mice</a> are polyandrous, meaning one female mates with several males. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/183841/original/file-20170829-6675-tjluy0.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/183841/original/file-20170829-6675-tjluy0.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/183841/original/file-20170829-6675-tjluy0.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=427&fit=crop&dpr=1 600w, https://images.theconversation.com/files/183841/original/file-20170829-6675-tjluy0.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=427&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/183841/original/file-20170829-6675-tjluy0.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=427&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/183841/original/file-20170829-6675-tjluy0.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=536&fit=crop&dpr=1 754w, https://images.theconversation.com/files/183841/original/file-20170829-6675-tjluy0.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=536&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/183841/original/file-20170829-6675-tjluy0.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=536&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 deer mouse.</span>
<span class="attribution"><a class="source" href="https://pixnio.com/fauna-animals/rats-mice-and-voles-pictures/deer-mouse-animal-peromyscus-maniculatus">Pixnio</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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<p>Mimicking nature by artificially manipulating a growth gene called igf2, researchers <a href="https://www.ncbi.nlm.nih.gov/pubmed/12728278">showed that</a> these smaller and larger offspring were due to genetics. In further support of the theory, placental mammals and marsupials including kangaroos and opossums have since been <a href="https://bmcgenomics.biomedcentral.com/articles/10.1186/1471-2164-9-205">found to</a> have signs of female resistance to such male manipulation. </p>
<p>How early did this mechanism evolve? Researchers have previously <a href="https://bmcgenomics.biomedcentral.com/articles/10.1186/1471-2164-9-205">suggested</a> it arose in live-born mammals, and would therefore be absent in egg-laying mammals – such as the platypus – and other vertibrates. </p>
<p>But that raises questions about all the reptiles, amphibians and fish which produce live young, since the same genetic manipulation would equally be in their males’ interests. To see if it was present, <a href="https://risweb.st-andrews.ac.uk/portal/en/researchoutput/asymmetric-paternal-effect-on-offspring-size-linked-to-parentoforigin-expression-of-an-insulinlike-growth-factor(f577a130-e1eb-49c6-aafe-0f65fe7e8017).html">we looked at</a> a Mexican fish called the amarillo or dark-edged splitfin (see lead image). </p>
<p>Along with co-researchers <a href="https://www.researchgate.net/profile/Yolitzi_Saldivar">Yolitzi Saldívar</a> and <a href="http://www.langebio.cinvestav.mx/?pag=365">Jean Philippe Vielle Calzada</a>, we crossed males and females from two distant populations of these fish, since they would not have evolved mechanisms which cancel one another out in the way that a single population is likely to have. Sure enough, the size of the embryos was influenced by the specific combination of father and mother. We found signs of male manipulation and probable resistance from the females. </p>
<p>Though based on a small sample size, this suggests that these mechanisms evolved much earlier than previously believed: fish split from other vertebrates some 200m years before live-bearing mammals appeared, dating back about 370m years in total. Whether it comes from a single evolution or from several in different lineages, we cannot yet tell. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/184393/original/file-20170901-27276-5i8lvq.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/184393/original/file-20170901-27276-5i8lvq.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/184393/original/file-20170901-27276-5i8lvq.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=605&fit=crop&dpr=1 600w, https://images.theconversation.com/files/184393/original/file-20170901-27276-5i8lvq.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=605&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/184393/original/file-20170901-27276-5i8lvq.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=605&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/184393/original/file-20170901-27276-5i8lvq.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=760&fit=crop&dpr=1 754w, https://images.theconversation.com/files/184393/original/file-20170901-27276-5i8lvq.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=760&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/184393/original/file-20170901-27276-5i8lvq.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=760&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Animal magic.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/evolution-biology-scheme-animals-isolated-on-293178890?src=TWxd03vTyW1iwPyOGI7ZqQ-1-39">Ekaterina</a></span>
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<p>One consequence of these genetic battles is the effect on reproductive compatibility within a species. The genetic mutations aimed at manipulating offspring that take place among males and females within a certain group of a species are like a sort of arms race. The genes continually adapt and counter-adapt to one another to try and further their reproductive interests. </p>
<p>If they then mate with an animal from a different group of the same species, their genetic mutations can have made them sufficiently unmatched over time that they are unable to reproduce – thus they are now two species. If this started happening much earlier in evolution than was previously thought, it is likely to have influenced how different groups of live-born animals diverged, including lizards, sharks and mammals. From little acorns, these are the kinds of big oak trees that can grow.</p><img src="https://counter.theconversation.com/content/82417/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Parents’ DNA try to manipulate one another in a bid to shape junior in their mould.Constantino de Jesús Macías García, Director of the Ecology Institute, Universidad Nacional Autónoma de México (UNAM)MIchael Ritchie, Professor of Evolutionary Biology and Speciation, University of St AndrewsLicensed as Creative Commons – attribution, no derivatives.