tag:theconversation.com,2011:/africa/topics/gene-editing-summit-23100/articlesGene editing summit – The Conversation2019-12-06T03:52:51Ztag:theconversation.com,2011:article/1284542019-12-06T03:52:51Z2019-12-06T03:52:51ZChina’s failed gene-edited baby experiment proves we’re not ready for human embryo modification<figure><img src="https://images.theconversation.com/files/305569/original/file-20191206-39018-1dfhe9r.jpg?ixlib=rb-1.1.0&rect=47%2C33%2C4446%2C2957&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The team used CRISPR on human embryos in a bid to render them resistant to HIV infection. But instead, they generated different mutations, about which we know nothing.</span> <span class="attribution"><span class="source">SHUTTERSTOCK</span></span></figcaption></figure><p>More than a year ago, the world was shocked by Chinese biophysicist He Jiankui’s attempt to use CRISPR technology to modify human embryos and make them resistant to HIV, which led to the birth of twins Lulu and Nana.</p>
<p>Now, crucial details have been revealed in a recent <a href="https://www.technologyreview.com/s/614764/chinas-crispr-babies-read-exclusive-excerpts-he-jiankui-paper/">release of excerpts</a> from the study, which have triggered a series of concerns about how Lulu and Nana’s genome was modified.</p>
<h2>How CRISPR works</h2>
<p>CRISPR is a technique that allows scientists to make precise edits to any DNA by altering its sequence.</p>
<p>When using CRISPR, you may be trying to “knock out” a gene by rendering it inactive, or trying to achieve specific modifications, such as introducing or removing a desired piece of DNA.</p>
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<a href="https://theconversation.com/what-is-crispr-gene-editing-and-how-does-it-work-84591">What is CRISPR gene editing, and how does it work?</a>
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<p>Gene editing with the CRISPR system relies on an association of two molecules. One is a protein, called Cas9, that is responsible for “cutting” the DNA. The other molecule is a short RNA (ribonucleic acid) molecule which works as a “guide” that brings Cas9 to the position where it is supposed to cut.</p>
<p>The system also needs help from the cells being edited. DNA damage is frequent, so cells regularly have to repair the DNA lesions. The associated repair mechanisms are what introduce the deletions, insertions or modifications when performing gene editing.</p>
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<h2>How the genomes of Lulu and Nana were modified</h2>
<p>He Jiankui and his colleagues were targeting a gene called CCR5, which is necessary for the HIV virus to enter into white blood cells (<a href="https://www.medicalnewstoday.com/articles/320987.php">lymphocytes</a>) and infect our body. </p>
<p>One variant of CCR5, called CCR5 Δ32, is missing a particular string of 32 “letters” of DNA code. This variant naturally occurs in the human population, and results in a high level of resistance to the most common type of HIV virus.</p>
<p>The team wanted to recreate this mutation using CRISPR on human embryos, in a bid to render them resistant to HIV infection. But this did not go as planned, and there are several ways they may have failed.</p>
<p>First, despite claiming in the abstract of their unpublished article that they reproduced the human CCR5 mutation, in reality the team tried to modify CCR5 <em>close</em> to the Δ32 mutation. </p>
<p>As a result, they generated different mutations, of which the effects are unknown. It may or may not confer HIV resistance, and may or may not have other consequences. </p>
<p>Worryingly, they did not test any of this, and went ahead with implanting the embryos. This is unjustifiable.</p>
<h2>The mosaic effect</h2>
<p>A second source of errors could have been that the editing was not perfectly efficient. This means that not all cells in the embryos were necessarily edited. </p>
<p>When an organism has a mixture of edited and unedited cells, it is called a “mosaic”. While the available data are still limited, it seems that both Lulu and Nana are mosaic. </p>
<p>This makes it even less likely that the gene-edited babies would be resistant to HIV infection. The risk of mosaicism should have been another reason not to implant the embryos.</p>
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Read more:
<a href="https://theconversation.com/designer-babies-wont-be-common-anytime-soon-despite-recent-crispr-twins-108342">'Designer' babies won't be common anytime soon – despite recent CRISPR twins</a>
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<p>Moreover, editing can have unintended impacts elsewhere in the genome. </p>
<p>When designing a CRISPR experiment, you choose the “guide” RNA so that its sequence is unique to the gene you are targeting. However, “off-target” cuts can still happen elsewhere in the genome, at places that have a similar sequence. </p>
<p>He Jiankui and his team tested cells from the edited embryos, and reported only one off-target modification. However, that testing required sampling the cells, which were therefore no longer part of the embryos - which continued developing. </p>
<p>Thus, the remaining cells in the embryos had not been tested, and may have had different off-target modifications. </p>
<p>This is not the team’s fault, as there will always be limitations in detecting off-target and mosaicism, and we can only get a partial picture. </p>
<p>However, that partial picture should have made them pause.</p>
<h2>A bad idea to begin</h2>
<p>Above, we have described several risks associated with the modifications made on the embryos, which could be passed on to future generations. </p>
<p>Embryo editing is only ethically justifiable in cases where the benefits clearly outweigh the risks.</p>
<p>Technical issues aside, the researchers did not even address an unmet medical need. </p>
<p>While the twins’ father was HIV-positive, there is already a well-established way to prevent an HIV-positive father from infecting embryos. This “<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779710/">sperm washing</a>” method was actually used by the team. </p>
<p>The only benefit of the attempted gene modification, if proven, would have been a reduced risk of HIV infection for the twins later in life.</p>
<p>But there are safer existing ways to control the risk of infection, such as condoms and mandatory testing of blood donations.</p>
<h2>Implications for gene editing as a field</h2>
<p>Gene editing has endless applications. It can be used to <a href="https://www.nature.com/articles/d41586-019-02770-7">make plants such as the Cavendish banana more resistant to devastating diseases</a>. It can play an important role in the adaptation to climate change. </p>
<p>In health, we are already seeing <a href="https://www.npr.org/sections/health-shots/2019/11/19/780510277/gene-edited-supercells-make-progress-in-fight-against-sickle-cell-disease">promising results</a> with the editing of somatic cells (that is, non-heritable modifications of the patient’s own cells) in beta thalassemia and sickle cell disease.</p>
<p>However, we are just not ready for human embryo editing. Our techniques are not mature enough, and no case has been made for a widespread need that other techniques, such as preimplantation genetic testing, could not address.</p>
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Read more:
<a href="https://theconversation.com/experts-call-for-halt-to-crispr-editing-that-allows-gene-changes-to-pass-on-to-children-113463">Experts call for halt to CRISPR editing that allows gene changes to pass on to children</a>
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<p>There is also much work still needed on governance. There have been individual calls for a moratorium on embryo editing, and expert panels from the <a href="https://www.nature.com/articles/d41586-019-00942-z">World Health Organisation</a> to <a href="https://en.unesco.org/news/unesco-panel-experts-calls-ban-editing-human-dna-avoid-unethical-tampering-hereditary-traits">UNESCO</a>.</p>
<p>Yet, no consensus has emerged.</p>
<p>It is important these discussions move <a href="https://www.nature.com/articles/d41586-019-03525-0">in unison</a> to a second phase, where other stakeholders, such as patient groups, are more broadly consulted (and informed). Engagement with the public is also crucial. </p>
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<p><em>Correction: this article originally described RNA (ribonucleic acid) as a protein, rather than a molecule.</em></p><img src="https://counter.theconversation.com/content/128454/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Dimitri Perrin has received funding from the Australian Research Council (ARC), the Australian-French Association for Innovation and Research (AFRAN), and the Advance Queensland programme.</span></em></p><p class="fine-print"><em><span>Gaetan Burgio receives funding from the National Health and Medical Research Council (NHMRC), the Australian Research Council (ARC), the National Collaborative Research Infrastructure Strategy (NCRIS) via the Australian Phenomics Network (APN) ,Universities Australia and the Natural Science Foundation in China (NSFC).</span></em></p>A number of things may have gone wrong when researchers edited Chinese twins Lulu and Nana’s genome. Either way, the failed experiment is a cautionary tale for us all.Dimitri Perrin, Senior Lecturer, Queensland University of TechnologyGaetan Burgio, Geneticist and Group Leader, The John Curtin School of Medical Research, Australian National UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1079382018-12-03T11:33:39Z2018-12-03T11:33:39ZYouTube, persuasion and genetically engineered children<figure><img src="https://images.theconversation.com/files/248148/original/file-20181130-194947-qg38fg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">In a masterfully manipulative Youtube video, He Jiankui tells the world about the first genetically edited babies.</span> <span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Genetic-Frontiers-Gene-Edited-Babies/95551dbf28c24ab086bd60d11c1bcf6b/51/0">AP Photo/Mark Schiefelbein</a></span></figcaption></figure><p>On Sunday, Nov. 25, the scientist He Jiankui claimed the birth of the world’s first genetically engineered children: twins, created by IVF, their DNA altered at fertilization. Changes like these, because they’re inheritable – “editing the germline” – are widely prohibited by law and avoided by scientific consensus. If He really did this, it’s a very big step across a very bright line.</p>
<p>Also, He announced the feat in a YouTube video.</p>
<p>The strangeness of this choice cannot be overstated. Groundbreaking achievements normally appear in prestigious journals, with extensive data, after rigorous peer review. Announcing the accomplishment on YouTube is the social media equivalent of walking out the front door and yelling, “Guess what, everybody? I’m the first to engineer a human being! And the kids are already here – they’re twins!” The timing of the video’s release – on the eve of a major international conference on genome editing, <a href="https://theconversation.com/tension-as-scientist-at-centre-of-crispr-outrage-speaks-at-genome-editing-summit-107807">where He was scheduled to speak</a> – clearly had more to do with publicity than science. </p>
<p>Others have written on the <a href="https://www.theatlantic.com/science/archive/2018/11/first-gene-edited-babies-have-allegedly-been-born-in-china/576661/">science</a> and <a href="https://www.theguardian.com/science/2018/nov/27/gene-edited-babies-no-one-has-moral-warrant-go-it-alone">ethics</a> involved. I’m a writer, so what interests me is persuasion: the way literary tools, like story and metaphor, help pave the way for cutting-edge biotechnology. Researching <a href="https://mitpress.mit.edu/books/fables-and-futures">a forthcoming book</a> on this topic, I came to see that human-focused biotech and persuasion form a single system: for the biotech to be adopted, the public has to accept it first. He’s video is a textbook bid for acceptance, an argument for germline editing aimed at the general public. </p>
<p>But the video is a low-rent production. It’s just He, standing in a lab, talking to the camera in English (it’s subtitled). As such, the video doesn’t hold a candle to the polished emanations of established research institutes or multimillion dollar corporations. The writing isn’t great either. Effective persuasion guides us lightly from one place to another: the lightest touch on your shoulder, redirecting your path. Listening to He is more like being yanked down a slippery slope. </p>
<p>And yet for precisely that reason, <a href="https://www.youtube.com/watch?v=th0vnOmFltc">the video</a> deserves a closer look: Seeing the pitch in its most obvious form, we can learn to recognize the patterns. </p>
<h2>The family success story</h2>
<p>The video begins with He beaming at the camera, describing “two beautiful little Chinese girls named Lulu and Nana,” a few weeks old, “as healthy as any other babies.” According to He, their parents, Mark and Grace, had always wanted to have a family. But Mark is HIV-positive, and stigma had deterred them. Now, because of He’s experiment – which was intended to make the twins permanently immune to HIV infection – a happy family exists. “The babies are home now with their mom Grace and their dad Mark,” He says. </p>
<p>“Mark” and “Grace,” their real names changed for privacy, may be real. Rhetorically, though, their function is to humanize a new technology. Ironically, that technology is changing what it means to be human in the first place.</p>
<h2>Portrait of a scientist</h2>
<p>Persuasion means crafting a persona, and He is clearly going for approachable scientist and family man. Identifying himself as “a father of two girls,” He also suggests his own humility, by saying, “Mark’s words taught me something I didn’t fully appreciate.” That lesson? “Gene surgery” helps more than a child: “We heal a whole family.” </p>
<p>That feigned humility doesn’t square with what He actually did: rushing to be first across the germline, thereby putting his experimental human subjects, and any of their descendants, at risk. Given all this, He’s assertion that he’s willing to brave controversy on behalf of the parents – “I’m willing to take the criticism for them” – rings just a tad hollow. </p>
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<span class="caption">Zhou Xiaoqin, left, and Qin Jinzhou, embryologists working with He Jiankui, view a time lapse image of embryos on a computer screen.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/China-Gene-Edited-Babies/a1b252903c424acf9609c03467a2fa6e/57/0">AP Photo/Mark Schiefelbein</a></span>
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<h2>Metaphors, omissions and weasel words</h2>
<p>Obviously, selling a new technology means putting it in the best possible light. Trying to do this, He makes an odd choice. Instead of “CRISPR-Cas9,” the common name, he insists on the phrase “gene surgery.” It’s a naked attempt to make CRISPR sound precise, like a molecular scalpel. That metaphor is misleading. CRISPR is improving in accuracy, but as geneticist Eric Topol wrote in <a href="https://www.nytimes.com/2018/11/27/opinion/genetically-edited-babies-china.html">The New York Times</a>, unintended edits still occur – “We don’t have the assurance yet that Crispr provides laserlike precision in editing” – and we might not always detect them. “Our ability to discern these changes is still rudimentary, and it is entirely likely that we will miss something,” Topol added. </p>
<p>But the surgery metaphor has another function: It likens the radically new to the comfortably familiar. He continues this theme with a second (mixed) metaphor: “The surgery removed the doorway through which HIV enters to infect people.” </p>
<p>A doorway is easy to imagine – and who could oppose slamming the door on AIDS? And yet the metaphor glosses over the complications of actual biology. It is true that people with a variation in the CCR5 gene have natural resistance to HIV. But other strains can infect the body <a href="http://doi.org/10.1097/COH.0b013e328324bbec">via a different protein</a>, which He left untouched. There is, in other words, more than one doorway. Complicating things further, having a variant CCR5 gene may protect you from HIV, but it also makes you more vulnerable to dying from <a href="https://doi.org/10.1084/jem.20051970">West Nile virus</a> or <a href="https://doi.org/10.1099/vir.0.000165">the flu</a>. </p>
<p>Also omitted from He’s video: the number of failed attempts required to get one successfully engineered baby. He’s team began with 22 embryos, but in the end only one pregnancy succeeded. Of the implanted twins, one, at best, is protected against HIV. (Our genes come in pairs; in one twin, only one gene was modified, not both.)</p>
<p>So when He asserts that “the surgery worked safely, as intended,” you have to remember that “safe,” like “health” and “choice,” is a useful weasel word: positive but vague, its meaning dependent on context. “Safe” could simply mean that the babies were born and appear to be okay. It does not mean they will be free from unanticipated effects, or protected from HIV.</p>
<h2>Reason, emotion and the dismissal of critics</h2>
<p>In arguments for new biotechnologies, it’s common to deride critics as fearful or irrational. He’s video is no exception. In it, he asserts that “the media hyped panic about Louise Brown’s birth as the first IVF baby.” Building on this theme in a second video (there are <a href="https://www.youtube.com/channel/UCn_Elifynj3LrubPKHXecwQ">five in all</a>), He <a href="https://www.youtube.com/watch?v=Qv1svMfaTWU&t=2s">inveighs against the phrase “designer baby</a>,” contrasting “vocal critics” with silently suffering families. By implication, you’re either pro-technology or pro-suffering. That’s a false binary, of course: Untested treatments can lead to suffering.</p>
<p>But He’s pitch also illuminates a common problem. In arguments like these, the categories of reason and emotion are invoked in contradictory ways. If people disagree with you, they’re dismissed as panicky and irrational. If they’re sympathetic parents who bolster your case, though, then their emotions are authoritative. In the second video, He contrasts parents and an unnamed naysayer: “[The parents] may not be the director of an ethics center quoted by the New York Times, but they are no less authorities on what’s right and wrong, because it’s their lives on the line.” </p>
<p>Actually, it’s their children’s lives on the line. Also, invoking sympathetic parents is itself an emotional appeal. </p>
<h2>Nana, Lulu: You’ve got mail</h2>
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<span class="caption">Lulu and Nana have their own email address.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/email-data-transfer-communications-promotion-spam-70575478?src=iQLYELHTOAfbDUIhk0dLbQ-1-9">Lightspring/Shutterstock.com</a></span>
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<p>Because independent verification is still lacking, reports about Lulu and Nana tend to use the phrase “if true.” It’s appropriate, somehow, that the possibility of human germline enhancement – insistently discussed and envisioned, from bioethics conferences to movies with genetically upgraded superheroes – still seems half-imaginary, a projection, an event with deep roots in the digital and shallow roots in the real. </p>
<p>At the end of the video, He invites you to email his lab and share your thoughts. But weirdly – and, by the end of the video, the bar for weird is very high — you can email Lulu and Nana themselves at DearLuluandNana@gmail.com. Perhaps they’ll have Twitter and Instagram accounts soon? Perhaps, one day, there’ll be a LuluAndNana.com, with an online fan club and emailed testimonials? In the meantime, the twins, engineered or not, expand into the world of information, where persuasion tries to reproduce itself. To go, in our biology-based metaphor, viral. </p>
<p>The twins’ email address is, of course, a PR gimmick. Emailing two Chinese infants (and why don’t they have their own addresses? They’re two people, after all) is about as meaningful as texting in a vote for this year’s “American Idol.” But we can learn something from the ploy: that inheritable human modification is too serious a matter for fake participation, and that a more substantive engagement is called for. If our species is to be engineered, then we all ought to have a say.</p><img src="https://counter.theconversation.com/content/107938/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>George Estreich 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>To announce the world’s first gene-edited babies, scientist He Jiankui did what movie directors do: release a trailer on YouTube. The video is a positive spin on unauthorized gene editing.George Estreich, Instructor, Oregon State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1076772018-11-27T12:40:11Z2018-11-27T12:40:11ZThe road to enhancement, via human gene editing, is paved with good intentions<figure><img src="https://images.theconversation.com/files/247373/original/file-20181126-140525-1pu35zm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A Chinese scientist claims he edited the DNA of twin girls during an in vitro fertilization procedure. </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/vitro-fertilisation-ivf-cell-under-microscope-764231488?src=ENuyRzFDhQbVzA4lEBm-Yg-1-0">CI Photos / Shutterstock.com</a></span></figcaption></figure><p>It <a href="https://apnews.com/4997bb7aa36c45449b488e19ac83e86d">appears</a> that researchers in China have facilitated the birth of the first “designer baby” – actually babies, twin girls who are supposedly genetically resistant to HIV. The scientist who created the embryos, as well as some American scientists like Harvard’s George Church, have praised the beneficent intent to producing a child who is resistant to disease. Who could argue with such good intentions? </p>
<p>But, once you can do this with one gene, you could someday do it with any gene – like those linked with <a href="https://doi.org/10.1038/mp.2016.45">educational attainment</a>. Those who praise the Chinese research have given no mechanism, or rules and regulations, that would allow human gene editing for only beneficent purposes. As the old proverb says, “The road to hell is paved with good intentions.”</p>
<p>For over 20 years I have focused my research on debates about <a href="https://www.press.uchicago.edu/ucp/books/book/chicago/P/bo3621106.html">human gene editing</a> and <a href="https://global.oup.com/academic/product/what-is-a-human-9780190608071?q=evans%2C%20john%20hyde&lang=en&cc=us">other biotechnologies</a>. I have watched these debates unfold, but I am shocked by the recent speed of developments.</p>
<p>The Chinese scientist, He Jiankui, claimed to have altered embryos for seven couples during fertility treatment in China. His goal was to disable a gene that encodes a gateway protein that allows the HIV virus to enter a cell. A woman nurtured two of those embryos and this month gave birth to non-identical twin girls who would, according to He, be resistant to HIV. </p>
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<a href="https://images.theconversation.com/files/247399/original/file-20181126-140525-15knyis.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/247399/original/file-20181126-140525-15knyis.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/247399/original/file-20181126-140525-15knyis.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/247399/original/file-20181126-140525-15knyis.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/247399/original/file-20181126-140525-15knyis.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/247399/original/file-20181126-140525-15knyis.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/247399/original/file-20181126-140525-15knyis.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/247399/original/file-20181126-140525-15knyis.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">Chinese scientist He Jiankui claims he helped make the world’s first genetically edited babies. He revealed the news on Monday, Nov. 26, in Hong Kong to one of the organizers of an international conference on gene editing.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Genetic-Frontiers-Gene-Edited-Babies/c5f8eb88e0e64fc3aed2b2388e0195ff/4/0">AP Photo/Mark Schiefelbein</a></span>
</figcaption>
</figure>
<p>Given the secrecy involved, it is difficult to verify He’s claim. The research wasn’t published in a peer-reviewed journal, the parents of the twins refused to speak with the media, and no one has tested the DNA of the girls to verify what He says is true. But what is more important for now is that there are scientists trying to create these enhanced humans who could pass on this trait to their offspring.</p>
<h2>Mainline and reform eugenics</h2>
<p>Creating an “improved” human species has long been the dream of eugenicists. The mainline, old school version of eugenics assumed that superior traits were found in particular races, ethnicities, and particularly in the United Kingdom, social classes. This logic culminated in the Holocaust where the Nazis concluded that some ethnic groups are genetically superior to others, and that the “inferior” ones should be exterminated and completely erased. </p>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/247409/original/file-20181126-140513-1m0g57a.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/247409/original/file-20181126-140513-1m0g57a.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/247409/original/file-20181126-140513-1m0g57a.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=807&fit=crop&dpr=1 600w, https://images.theconversation.com/files/247409/original/file-20181126-140513-1m0g57a.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=807&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/247409/original/file-20181126-140513-1m0g57a.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=807&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/247409/original/file-20181126-140513-1m0g57a.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1015&fit=crop&dpr=1 754w, https://images.theconversation.com/files/247409/original/file-20181126-140513-1m0g57a.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1015&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/247409/original/file-20181126-140513-1m0g57a.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1015&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This is a magazine published by the Office of Racial Policy of the Nazi Party while they were in power. The poster says: 60,000 Reichsmark is what this person suffering from hereditary illness costs the community in his lifetime. Fellow citizen, that is your money too.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Neues_Volk_eugenics_poster,_c._1937_(brightened).jpeg">Unknown author / Wikimedia Commons</a></span>
</figcaption>
</figure>
<p>The revelation of the Holocaust destroyed mainline eugenics, but a <a href="http://www.hup.harvard.edu/catalog.php?isbn=9780674445574">“reform” eugenics</a> arose in its wake in the 1950s. This brand of eugenics assumed that “superior traits” could be found among all ethnic groups. All that needed to happen was to get these superior people to produce more children and discourage those with inferior traits from reproducing. This turned out to be difficult.</p>
<p>But in the early 1950s, Francis Crick and James Watson <a href="https://doi.org/10.1038/171737a0">discovered the chemical structure of DNA</a>, which suggested that the genes of humans could be improved through chemical modification of their reproductive cells. A typical response was from prominent biologist <a href="https://news.ucsc.edu/2017/04/robert-sinsheimer-in-memoriam.html">Robert Sinsheimer</a> <a href="https://www.press.uchicago.edu/ucp/books/book/chicago/P/bo3621106.html">who wrote in 1969</a> that the new genetic technologies of the time allowed for “a new eugenics.” According to Sinsheimer, the old eugenics required selecting fit individuals to breed and culling the unfit. “The new eugenics would permit in principle the conversion of all of the unfit to the highest genetic level … for we should have the potential to create new genes and new qualities yet undreamed.”</p>
<h2>The slippery slope of the gene editing debate</h2>
<p>The modern ethical debate about human gene editing can be traced back to this era. The debate was implicitly set up like a slippery slope. </p>
<p>At the top of the slope was an act of gene editing deemed indisputably virtuous – a step most people were willing to take – such as repairing sickle cell anemia. However, the slope was slippery. It is very difficult to say that changing other traits that are not deadly, like deafness, are not equally acceptable. Once you figure out how to change one gene, you can change any gene, regardless of its function. If we fix sickle cell, why not deafness, or late onset heart disease, or a lack of “normal” intelligence, or as we approach the bottom, a lack of superior intelligence?</p>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/247407/original/file-20181126-140513-130f9qm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/247407/original/file-20181126-140513-130f9qm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/247407/original/file-20181126-140513-130f9qm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=795&fit=crop&dpr=1 600w, https://images.theconversation.com/files/247407/original/file-20181126-140513-130f9qm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=795&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/247407/original/file-20181126-140513-130f9qm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=795&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/247407/original/file-20181126-140513-130f9qm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=998&fit=crop&dpr=1 754w, https://images.theconversation.com/files/247407/original/file-20181126-140513-130f9qm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=998&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/247407/original/file-20181126-140513-130f9qm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=998&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Aldous Huxley wrote about a world in which everyone was genetically engineered and all opportunity was determined by your genetic code.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Associated-Press-International-News-United-King-/c36a840762e5da11af9f0014c2589dfb/3/0">AP Photo/Eraldo Peres</a></span>
</figcaption>
</figure>
<p>At the bottom of the slope was the dystopian world where nobody wants to end up. This is typically depicted as a society based on total genetic control of offspring where people’s lives and opportunities are determined by their genetic pedigree. Today the bottom of the slope is represented by the late 1990s movie “<a href="https://en.wikipedia.org/wiki/Gattaca">Gattaca</a>.” </p>
<h2>Stepping onto the slope</h2>
<p>In the 1970s, essentially all of the participants in the debate stepped onto the slope and approved of somatic gene therapy – a strategy for healing genetic diseases in the bodies of living people where genetic changes would not be passed to any offspring. Participants in the ethical debate about gene editing stepped onto this slope because they were confident that they had blocked any possible slide by creating a strong norm against the modification of DNA that passed to the next generation: the germline wall. (The germline means influencing not only the person modified, but their descendants.) </p>
<p>Somatic changes could be debated, but researchers would not move beyond the wall to change people’s inheritance – to change the human species as the eugenicists had long desired. Another barrier to the road to hell that turned out to be permeable was the wall between blocking disease and enhancing an individual. Scientists could try to use gene editing to avoid genetic diseases, like sickle cell disease, but not to create “improved” humans.</p>
<p>The recent actions of the Chinese scientist leap over both the germline and the enhancement walls. It is the first known act of human germline gene editing. These twin girls may pass their newfound resistance to HIV to their own children. It is also not meant to avoid a genetic disease like sickle cell anemia, but to create an enhanced human, albeit an enhancement made in the name of fighting infectious disease.</p>
<h2>Calling for a new wall</h2>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/qviOJRO2g0c?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">A Chinese researcher claims that he helped create the world’s first genetically edited babies.</span></figcaption>
</figure>
<p>Unlike in earlier years of the human gene editing debate, we are given no argument for where these applications would stop. Those advocating the Chinese scientist’s use of gene editing do not point to a wall further down the slope that can be used to reassure ourselves that by allowing this presumably beneficent application we will not eventually end up at the bottom. Many scientists seem to think that a wall can be constructed with “disease” applications in the acceptable part of the slope and “enhancement” in the unacceptable part below. </p>
<p>However, how one defines “disease” is notoriously fluid, with pharmaceutical companies frequently creating new diseases to be treated in a process sociologists call <a href="https://books.google.com/books?hl=en&lr=&id=hYpZjDD67dkC&oi=fnd&pg=PR13&dq=medicalization&ots=GKrE5_HLc4&sig=u-a7FNTRQn3Slg53MSS_Rs_vmBw#v=onepage&q=medicalization&f=false">medicalization.</a> Moreover, is deafness a disease? Many deaf people do not think so. We also cannot simply rely upon the medical profession to define disease, as some practitioners are engaged in activities that are more aptly described as enhancement (think plastic surgery). A <a href="https://doi.org/10.17226/24623">recent report</a> by the National Academy of Sciences concluded that the distinction between disease and enhancement is hopelessly muddled.</p>
<p>So, while the scientists defending the first enhanced baby may be right that this is a moral good, unlike previous debaters they have given society no walls or barriers that allow us to confidently walk on to this new slippery slope. It is just dodging responsibility to say that “<a href="https://apnews.com/4997bb7aa36c45449b488e19ac83e86d">society will decide what to do next,</a>” as did He, or to say that the research “<a href="https://apnews.com/4997bb7aa36c45449b488e19ac83e86d">is justifiable,</a>” without defining a limit, as did Harvard University’s George Church. </p>
<p>For a responsible debate, participants must state not only their conclusion about this particular act of enhancement, but also where they will build a wall and, critically, how this wall will be maintained in the future.</p>
<p><em>This article was updated on November 29, 2018, to refer to He Jiankui by his last name.</em></p><img src="https://counter.theconversation.com/content/107677/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>John Evans 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 Chinese scientist has revealed he edited the DNA of twin girls born through in vitro fertilization. These girls are designed to be resistant to HIV. Is the edit a medical necessity or an enhancement?John Evans, Professor of Sociology, University of California, San DiegoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/669182016-10-24T06:41:20Z2016-10-24T06:41:20ZCRISPR gene-editing controversy shows old ideas about East and West still prevail<figure><img src="https://images.theconversation.com/files/142827/original/image-20161024-15941-xkgcfv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">CRISPR uses segments of bacterial DNA that can make targeted cuts in a genome when paired with a specific guide protein.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/kyz/3340435836/">Stuart Caie/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>The debate that followed initial experiments using the <a href="https://www.nap.edu/catalog/23405/gene-drives-on-the-horizon-advancing-science-navigating-uncertainty-and">CRISPR-Cas9</a> genome editing tool show that old stereotypes about Asia still resonate in the West. </p>
<p>CRISPR-Cas9 is a gene editing tool that was <a href="http://science.sciencemag.org.libproxy1.nus.edu.sg/content/sci/337/6096/816.full.pdf">first demonstrated</a> in US and Swedish labs in 2012. Basically, it uses segments of bacterial DNA that can make targeted cuts in a genome when paired with a specific guide protein (in this case, Cas9). </p>
<p>The technique is relatively uncomplicated compared with previous genome editing tools, which have been studied by scientists for more than 50 years. If applied to the genome of human germline cells, which pass on genetic material to produce human embryos, CRISPR-Cas9 has – at least in theory – the capability to <a href="http://www.nytimes.com/2015/11/15/magazine/the-crispr-quandary.html?_r=0">alter humanity</a> as we understand it. </p>
<p>Once certain genes are introduced or removed in germline cells (also known as gametes), the changes are passed onto the next generation. Given its potential to be misapplied towards eugenic ends and related ethical concerns, <a href="http://www.nature.com/news/don-t-edit-the-human-germ-line-1.17111">scientists generally agree</a> that genetic modification of human gametes and embryos should not be done for reproductive purposes. </p>
<p>But it was less clear if genome editing in a human embryo that could not be used for reproduction was ethically acceptable. </p>
<h2>Confecting controversy</h2>
<p>In the spring of 2015, Junjiu Huang and his research team at Sun Yat-sen University in Guangzhou, China, used CRISPR-Cas9 to edit the genome of <em>non-viable</em> human embryos. The <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417674/">publication of that study</a> generated <a href="http://www.nytimes.com/2015/06/30/science/a-scientific-ethical-divide-between-china-and-west.html">a huge amount of controversy</a>, with an article in the New York Times claiming:</p>
<blockquote>
<p>medical researchers in China are stepping over ethical boundaries long accepted in the West.</p>
</blockquote>
<p>But such research could have also been possible in some Western countries, such as in the UK.</p>
<p>A recurring theme in such controversies is the concern that responsible conduct leads to loss of <a href="http://www.bbc.com/future/story/20160804-china-may-be-the-future-of-genetic-enhancement">competitive advantage</a>, when the same rules do not apply to everyone. </p>
<p>It’s often assumed that countries in Asia have an advantage in moving ahead rapidly with gene editing, stem cell research, cloning and other biotech fields because they don’t share the same religious or political views about the human embryo that prevail in Western countries.</p>
<p>This concern reached a high point for stem cell research when former <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744932/">US president George W Bush introduced a ban</a> on federal funding for research involving newly created human embryonic stem cell lines. </p>
<p><a href="https://papyrus.bib.umontreal.ca/xmlui/bitstream/handle/1866/724/Isasi-Knoppers%20Mind%20the%20Gap_Policy%20Approaches%20to%20Embryonic.pdf;jsessionid=6013B7BCAF7C73ECC794B0EB089BFCF0?sequence=1">Countries such as Germany and Italy</a> also impose legal restrictions on research involving the human embryo. In Germany, memory of <a href="https://theconversation.com/is-it-ethical-to-use-data-from-nazi-medical-experiments-39928">inhumane medical experiments</a> carried out by the Nazi regime has led to a comprehensibly more conservative stance towards technologies that could be misapplied toward eugenic ends. </p>
<p>And Italy is opposed to such research due mainly to the religious belief that a human embryo should be treated as morally equivalent to a person. It’s less clear whether non-viable embryos, such as those used by Huang, would enjoy a similar moral status. </p>
<p>In contrast – and by implication – the research culture in non-Western countries is portrayed as a free-for-all. But such an appraisal is clearly misleading. </p>
<p>For a start, this view assumes that there is a substantial difference in standards between Western countries and their non-Western competitors. The Chinese research team were perceived to have succeeded in their scientific endeavour primarily because China was assumed to have little or no regulatory control over human embryo research.</p>
<p>It also adopts a blinkered view of the competitive landscape: scientific progress depends on far more than differences in the ethical and regulatory environments. <a href="https://www.ncbi.nlm.nih.gov/books/NBK26378/">Many other factors apply</a>, ranging from social and economic systems, the availability of funding and institutional arrangements, and research networks and skills.</p>
<p>Finally, it fails to critically assess the limitations of its own reductionist perception. In his classic work Orientalism, <a href="http://www.postcolonialweb.org/poldiscourse/pol11.html">Edward Said explained</a> how the West had created a dichotomy between the Orient, as irrational, backward and culturally unsophisticated, and itself, as rational, advanced and culturally refined. </p>
<p>Said noted that this kind of blindness was just as much a part of the insights into how the “other” is understood, as it is of and in relation to the “self”. </p>
<h2>Shared ethical standards</h2>
<p>Contrary to what <a href="http://qz.com/441423/why-china-wont-listen-to-western-scientists-about-genetically-modifying-the-human-embryo/">some initial media reports</a> suggested, Huang’s study did not violate generally accepted international guidelines or even the regulatory requirements of scientifically advanced countries. </p>
<p><a href="http://legal.un.org/docs/?symbol=A/RES/59/280">International law</a> does not prohibit research on human embryos, although there’s a <a href="http://www.isscr.org/docs/default-source/guidelines/isscr-guidelines-for-stem-cell-research-and-clinical-translation.pdf?sfvrsn=2">general consensus</a> that all such research should be limited to within 14 days of embryonic development. The embryos are then to be destroyed.</p>
<p>Critically, only non-viable embryos (known technically as dispermic <a href="http://phenomena.nationalgeographic.com/2015/04/22/editing-human-embryos-so-this-happened/">tripronuclear zygotes</a>) were used in Huang’s research. These are embryos that would not be biologically capable of developing into an organism that looks anything like a human foetus. </p>
<p>For the purposes of the study, it was only necessary for the embryos to develop for about 48 hours (or to an eight-cell stage), before they were analysed to better understand the efficacy of the gene-editing technique under investigation.</p>
<p>Human embryo research is subject to <a href="https://www.ncbi.nlm.nih.gov/pubmed/26791577">ethical and regulatory controls in China</a>, just as it is in Western countries. Indeed, apart from some procedural or workflow differences, the requirements that these controls give effect to don’t differ significantly from the requirements in international guidelines and in the regulatory provisions of countries that allow the research. </p>
<p>Chinese regulations impose informed consent and ethics review requirements, for instance, as well as prohibit the application of such research for any reproductive purposes. These are no different from regulatory requirements that apply in many Western European and North American countries.</p>
<h2>The nature of competition</h2>
<p>The relationships between science and its broader social or political environment is a complex one. It should not be surprising to find that the <a href="https://hbr.org/1990/03/the-competitive-advantage-of-nations">nature of competition differs significantly</a> from one country to another. </p>
<p>Competition could be directed towards identifying problems that relate to the health and well-being of people, or it could be aimed at providing accurate and compelling information to promote better choices. In other words, <a href="http://www.nature.com/nmeth/journal/v11/n7/full/nmeth.3026.html">competition could also lead to collaboration</a>.</p>
<p>Where regimes of research governance are concerned, an even broader spectrum of approaches can exist. It is not especially insightful to speculate on scientific progress on the basis of one narrowly construed indicator which, in the context of this debate, is the stringency of ethical or regulatory control in the East versus the West.</p>
<p>Thankfully, baseless assumptions gave way to fair-minded engagement. In December 2015, the US National Academy of Sciences, US National Academy of Medicine, Chinese Academy of Sciences and the UK Royal Society organised an <a href="http://www.nationalacademies.org/gene-editing/Gene-Edit-Summit/index.htm">International Summit</a> in Washington DC on the scientific developments in human gene editing, and related ethical and governance issues. </p>
<p>A <a href="https://www.nap.edu/read/21913/chapter/1#6">statement released</a> from the meeting proposes that gene editing of human eggs, sperms and embryos should be allowed, but only as research in the laboratory. Just as Huang’s research had done.</p>
<p>Gene editing tools, when better understood, could help prevent life-threatening and seriously debilitating conditions, and could help treat currently incurable conditions. Still, for the time being, gene editing is not to be applied in the clinic. </p>
<p>Since this meeting, <a href="http://www.nature.com/news/uk-scientists-gain-licence-to-edit-genes-in-human-embryos-1.19270">scientists in the UK</a> have successfully obtained regulatory approval to use CRISPR-Cas9 in healthy human embryos in order to better understand early embryo development. These genome-edited embryos will only be studied for up to seven days of development, after which they will be destroyed.</p>
<h2>Excesses of Orientalism</h2>
<p>There was rampant speculation in the media less than two decades ago that Western countries would lose out to their non-Western competitors in developing <a href="http://www.stemcellfoundation.net.au/docs/fact-sheets/fact-sheet-4---therapeutic-cloning-(somatic-cell-nuclear-transfer).pdf?sfvrsn=5">therapeutic cloning</a>, a cornerstone technology in <a href="https://www.ncbi.nlm.nih.gov/pubmed/23809322">regenerative medicine</a>. </p>
<p>Ironically, it was in Japan that a new scientific method (known as <a href="http://www.the-scientist.com/?articles.view/articleNo/32765/title/Cell-Re-Programmers-Take-the-Nobel/">induced pluripotent stem cell</a> technique) was developed to allow cloning without destroying a human embryo.</p>
<p>For a time, both after cloning and Huang’s CRISPR experiment, various Western media depicted non-Western societies in ways that were static and crude. This process of “othering” Asia, broadly referred to as <a href="http://www.newworldencyclopedia.org/entry/Orientalism">Orientalism</a>, is problematic for its reductionism and stereotyping. </p>
<p>Sadly, its excesses seem impossible to edit out of human history.</p><img src="https://counter.theconversation.com/content/66918/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Calvin Wai-Loon Ho receives funding from the Singapore government.</span></em></p>Controversy over a Chinese study that used CRISPR-Cas9 gene-editing technology shows how the West still looks at the East through the lens of Orientalism.Calvin Wai-Loon Ho, Assistant Professor of Bioethics, National University of SingaporeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/523262015-12-16T15:52:23Z2015-12-16T15:52:23ZHow close are we to successfully editing genes in human embryos?<figure><img src="https://images.theconversation.com/files/106025/original/image-20151215-23205-32o10z.jpg?ixlib=rb-1.1.0&rect=0%2C31%2C639%2C432&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Eight cells in an embryo at three days.</span> <span class="attribution"><a class="source" href="https://en.wikipedia.org/wiki/Human_embryogenesis#/media/File:Embryo,_8_cells.jpg">ekem, Courtesy: RWJMS IVF Program/wikimedia</a></span></figcaption></figure><p>An important international summit on human gene editing <a href="http://www.theguardian.com/science/2015/dec/03/gene-editing-summit-rules-out-ban-on-embryos-destined-to-become-people-dna-human">recently recommended</a> that researchers go ahead with gene editing human embryos, but keep revisiting how and when such modifications would be appropriate in the clinic. The decision came after some scientists <a href="http://www.nytimes.com/2015/12/04/science/crispr-cas9-human-genome-editing-moratorium.html?_r=0">called for a moratorium</a> on such research.</p>
<p>The recommendation was always going <a href="https://www.washingtonpost.com/opinions/the-great-potential--and-great-risks--of-gene-editing/2015/12/11/ea1607a4-9a09-11e5-8917-653b65c809eb_story.html">to be controversial</a>, with many people concerned that the technology, which could be used to prevent parents from passing on genetic diseases to their children, will be misused and lead to permanent changes in the human gene pool.</p>
<p>But how close are we – is there really reason to be concerned at this point?</p>
<h2>Laboratory promise</h2>
<p>Gene editing of the human germline – those cells that form the sperm and eggs and, from a fertilised egg, will generate every cell in the human body – is different from other types of genetic editing because changes in those cells will be inherited by future generations, to become a permanent change in the human make-up.</p>
<p>Working on human germline cells at the very earliest stages of the formation of an embryo, just after an egg has been fertilised and then implants itself in the womb, is of course impossible to do in a pregnant woman. In <a href="http://www.gurdon.cam.ac.uk/research/surani">my lab</a>, where our focus is on early development, we approach this research using mice and, more recently, by simply growing human cells in a culture dish. In this way we have managed to identify some of the earliest genetic events that “specify” a stem cell to become a germline cell.</p>
<p>At the same time the technology underpinning gene editing, such as the <a href="https://theconversation.com/explainer-crispr-technology-brings-precise-genetic-editing-and-raises-ethical-questions-39219">CRISPR/Cas9</a> – a fast, easy and unprecedentedly precise method for targeting edits to specific genes – is becoming widespread across science. Together with the new ways of studying germline cells in the lab, this is offering a real chance for scientists and the public to consider whether or not editing of the human germline has merit – before any harm can be done.</p>
<p>We can now <a href="http://dev.biologists.org/content/141/2/245">create human “primordial germ cells”</a>, the precursors to eggs and sperm, from embryonic stem cells. It is a delicate and time-consuming procedure, and the resulting cells do not survive beyond the very early stages of development – partly because we have yet to reproduce the conditions that they are designed to thrive in. What we have been able to show is that some of the earliest steps in the development of human primordial germ cells are [different from those in mice](http://www.cell.com/cell/fulltext/S0092-8674(14). This is important as most of the previous results in this area have come from mouse models, indicating that such information cannot actually be wholly extrapolated to describe humans. </p>
<p>Last year, we also managed to generate primordial <a href="http://www.nature.com/news/rudimentary-egg-and-sperm-cells-made-from-stem-cells-1.16636">germ cells from adult body cells</a>, such as human skin cells. We take body cells that have been programmed to revert back into stem cells, and add chemical factors to “re-specify” them as primordial germ cells.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/106046/original/image-20151215-23172-145nf55.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/106046/original/image-20151215-23172-145nf55.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=593&fit=crop&dpr=1 600w, https://images.theconversation.com/files/106046/original/image-20151215-23172-145nf55.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=593&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/106046/original/image-20151215-23172-145nf55.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=593&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/106046/original/image-20151215-23172-145nf55.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=745&fit=crop&dpr=1 754w, https://images.theconversation.com/files/106046/original/image-20151215-23172-145nf55.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=745&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/106046/original/image-20151215-23172-145nf55.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=745&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">It is possible to create gene-edited sperm in mice. But humans may be a different story.</span>
<span class="attribution"><a class="source" href="https://simple.wikipedia.org/wiki/Semen#/media/File:Sperm-20051108.jpg">Gilberto Santa Rosa from Rio de Janeiro, Brazil/wikimedia</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>While these cells don’t survive long either, experiments have shown that introducing such cells into the testes and ovaries of in mice does allow them to continue their development and maturation into sperm and eggs. Remarkably, such mice were able to <a href="https://www.sciencemag.org/content/338/6109/971.full">give birth to healthy offspring</a> raising the prospect of reprogrammed skin cells creating living human beings. For that reason it certainly makes sense to carry out similar studies using primates. Further research might also make it possible to develop working sperm and egg cells entirely in a culture dish. </p>
<h2>Finished blueprint?</h2>
<p>Looking ahead, it is clear that there already is a potential template for editing the human germline. Genome-sequencing methods could also provide for additional checks to ensure that no inadvertent mutations or “off-target” effects have occurred during the editing procedures. </p>
<p>What’s more, if viable sperm and eggs could be grown in the lab from primordial germ cells, they could be used to generate fertilised embryos. Such “pre-implantation” embryos could also be further screened (as is routine now in the in-vitro fertilisation procedure) to ensure transfer to the womb of only those embryos that are free from specific mutations. </p>
<p>So how could this work in a clinic? Imagine combining the procedures in one patient, for example a woman with a disease-causing mutation who does not wish to pass this mutation to her child. Starting with a cell taken from her skin, this is reprogrammed to a primordial germ cell, in which the DNA is then edited to remove the mutated gene. The primordial germ cell is developed into an egg and used to create an embryo for IVF, to be screened and transplanted back into her womb. The child and its subsequent descendants would be free of the mutated gene.</p>
<p>There’s a reason why the summit carefully considered such massive implications and nevertheless recommended to pursue such research. Without making further gains in our knowledge about the fundamental processes in early germ cell and embryo development – starting with growing germ cells for longer in the culture dish – we will not know what we can and cannot safely achieve with the new gene-editing technologies. We are still some way from being able to contribute the necessary biological evidence to society’s debate about which, if any, of these technologies to pursue.</p><img src="https://counter.theconversation.com/content/52326/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Azim Surani receives funding from The Wellcome Trust and Cancer Research UK</span></em></p>We’re not quite there yet but there is already a potential blueprint for editing the human germline.Azim Surani, Director of Germline and Epigenomics Research at the Gurdon Institute, University of CambridgeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/518432015-12-07T10:46:38Z2015-12-07T10:46:38ZWhy treat gene editing differently in two types of human cells?<figure><img src="https://images.theconversation.com/files/104520/original/image-20151206-29716-m84d6a.jpg?ixlib=rb-1.1.0&rect=0%2C1016%2C6116%2C4101&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A snip here, but not a snip there?</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-303373844/stock-photo-gene-editing-health-care-concept-as-molecular-scissors-cutting-a-dna-strand-as-a-medical-science.html">DNA image via www.shutterstock.com</a></span></figcaption></figure><p>At the conclusion of the recent <a href="http://www.nationalacademies.org/gene-editing/Gene-Edit-Summit/index.htm">International Summit on Human Gene Editing</a> in Washington, DC, its organizing committee released a <a href="http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=12032015a">much-anticipated statement</a> recommending how human genetic engineering should be regulated. Co-organized by US, UK and Chinese national academies, the summit gathered preeminent researchers, clinicians and ethicists to grapple with how new gene editing technologies – particularly the method known as CRISPR – should be used. As CRISPR-cas9 is refined in the lab, several <a href="http://www.wired.co.uk/news/archive/2015-04/23/gene-editing-human-embryos-first-controversial-study">actual</a> and <a href="http://www.theguardian.com/science/2015/sep/18/uk-scientists-seek-permission-to-genetically-modify-human-embryos?CMP=share_btn_tw">proposed</a> trials using the technique have raised ethical concerns. </p>
<p>Somewhat surprisingly, the summit statement was generally supportive of human gene editing. It suggested that research into genetic modifications should continue as long as it doesn’t lead to a pregnancy. The statement opposed (for now) clinical use of <a href="http://ghr.nlm.nih.gov/glossary=germline">germline</a> modifications – those are genetic changes that would be in every cell of a resulting baby and be passed on to future generations. The committee, though, approved of clinical use of <a href="http://ghr.nlm.nih.gov/glossary=somaticcell">somatic</a> (body) cell gene therapies that affect only the treated individual, not future offspring.</p>
<p>There is not yet consensus within the gene editing community over what the ethical and legal limits to techniques like CRISPR should be. The statement contributes a reasonably clear position: research into using gene editing to cure diseases should continue. But by saying we should hold off on non-research changes to genes in sperm, eggs and embryos, I’d suggest the ethical distinction they make between modifying body cells and germline cells is tenuous. This leads to inconsistent regulatory standards that risk either underregulating somatic therapies or overregulating germline therapies.</p>
<h2>Both yes and no</h2>
<p>The committee’s position is at once liberal and conservative.</p>
<p>On the one hand, it promotes more research into germline editing, and does not suggest forever shutting the door on reproductive applications – policies are to be revisited regularly. <a href="http://www.nature.com/news/don-t-edit-the-human-germ-line-1.17111">Others</a> had <a href="https://www.washingtonpost.com/news/innovations/wp/2015/09/08/why-theres-an-urgent-need-for-a-moratorium-on-gene-editing/">called</a> for a <a href="https://theconversation.com/crispr-cas-gene-editing-technique-holds-great-promise-but-research-moratorium-makes-sense-pending-further-study-43371">stronger moratorium</a> or even a ban on such research. These voices are <a href="http://www.ipscell.com/2015/12/perspectives-no-moratorium-from-organizers-of-geneeditsummit/">concerned</a> that medical risks and ethical pitfalls have not been adequately taken into account. </p>
<p>But the committee’s position is also conservative, as it does not imply a major change to gene-editing “business as usual” in the host countries. Existing <a href="http://www.businessinsider.sg/china-edited-human-genome-laws-2015-4/#.VmJ29Y9OKM8">Chinese guidelines</a> and <a href="http://www.lawandreligionuk.com/2015/09/08/genome-editing-of-human-cells/">UK law</a> are already in line with this new statement. They ban reproductive germline modifications. But non-reproductive germline research and clinical somatic therapy are permitted under certain conditions. </p>
<p>The US situation is more complicated. While federal funding is <a href="http://www.nih.gov/about-nih/who-we-are/nih-director/statements/statement-nih-funding-research-using-gene-editing-technologies-human-embryos">not presently provided</a> for germline research, no ban on private research (or, for that matter, clinical germline modification) is in place. But since the committee’s statement does not urge countries to provide national funding for germline research, it’s consistent with the US regulatory landscape.</p>
<h2>Body cells or embryos</h2>
<p>The committee statement – also in line with many current regulations – makes a careful distinction between clinical somatic cell gene therapies and germline cell therapies. So, the recent <a href="http://www.theguardian.com/science/2015/nov/05/baby-girl-is-first-in-the-world-to-be-treated-with-designer-immune-cells">infusion of genetically modified white blood cells</a> that saved the life of a baby with leukemia, Layla Richardson, would be acceptable. But it would have been unacceptable if the intervention had also affected her egg cells, and thus future children.</p>
<p>There are three important differences between the two approaches.</p>
<ol>
<li><p>Somatic therapies target genes in specific types of cells (lung cells, skin cells, blood cells, etc), while germline modifications, applied to embryos, sperm or eggs, alter the genes in all the resultant person’s cells.</p></li>
<li><p>Somatic cell modifications are noninheritable, affecting only the treated individual. Germline modifications <a href="http://www.ncbi.nlm.nih.gov/books/NBK21894/">would be passed on</a> to future generations.</p></li>
<li><p>Somatic cell therapies have been tested and implemented for <a href="http://www.ncbi.nlm.nih.gov/pubmed/23618815">much longer</a>. The first somatic trials occurred two and a half decades ago, while human germline editing studies have <a href="http://dx.doi.org/10.1007/s13238-015-0153-5">only just begun</a> this year.</p></li>
</ol>
<p>But do those differences merit a significantly different regulatory approach – a moratorium for clinical germline editing, versus standard regulation for somatic therapies? I would, in line with <a href="http://jmp.oxfordjournals.org/content/16/6/641.short">a critique</a> that appeared during the advent of somatic therapies, suggest not. </p>
<h2>Does the ethical distinction make sense?</h2>
<p>One reason for the different approaches concerns risk levels. Germline gene therapy both has greater impact and is less established than somatic gene therapy. This certainly merits more caution. Regulatory bodies should be more reluctant to approve therapies with wide-ranging, uncertain effects. It’s sensible to demand strong evidence of safety and reasonable risk/benefit ratios before new technologies are made available clinically. </p>
<p>This is the approach we take to all novel biomedical interventions. Indeed, when somatic cell therapy was first proposed, it was also a new therapy with <a href="http://www.nytimes.com/1993/09/01/health/personal-health-the-promise-and-the-pitfalls-of-gene-therapy.html">potentially severe risks</a>. <a href="http://www.fda.gov/downloads/BiologicsBloodVaccines/SafetyAvailability/UCM148113.pdf">Careful regulation</a>, rather than a blanket moratorium, was needed to manage those risks. A similar approach would make sense for germline modifications.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/104540/original/image-20151206-8664-x67jw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/104540/original/image-20151206-8664-x67jw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/104540/original/image-20151206-8664-x67jw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/104540/original/image-20151206-8664-x67jw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/104540/original/image-20151206-8664-x67jw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/104540/original/image-20151206-8664-x67jw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/104540/original/image-20151206-8664-x67jw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/104540/original/image-20151206-8664-x67jw.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">Does what kind of cells you’re targeting matter?</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/kaibara/3075268200">Umberto Salvagnin</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>The committee emphasizes in its statement another reason for the distinction between editing genes in the two kinds of cells. Heritability of germline changes is a novel form of risk not adequately accounted for in current regulatory frameworks. </p>
<p>However, I would argue the long-term risks of inheritability unique to germline modification are much less certain and actually more manageable than the short-term risks of harmful modifications shared by somatic therapies. The therapy used on baby Layla was the first of its kind tried in humans, and there was a serious risk of rejection that could have increased her already acute suffering. Those risks needed to be weighed heavily. But it seems unlikely that the overall risk profile would have changed significantly if the treatment would have also have affected the baby’s future children. </p>
<p>In this sort of case, there would be at least a decade and a half gap between when a modification occurs and the point at which the affected individual may begin to bear children. That’s ample time to detect abnormalities and develop mitigation strategies, including further corrective germline modification. And in any case, I’d argue it would be irresponsible to allow near-term suffering in cases like baby Layla’s in order to avoid much more uncertain long-term risks to individuals who don’t even exist yet, and may not exist but for the treatment itself.</p>
<p>A final reason for the differentiation is that some people find germline modification to be a morally objectionable form of genetic engineering. Concerns abound that it involves <a href="http://www.un.org/apps/news/story.asp?NewsID=52172#.VmKYP49OKM8">playing God</a>, <a href="http://www.councilforresponsiblegenetics.org/ViewPage.aspx?pageId=101">opens the door to eugenics</a> and will lead to <a href="http://www.huffingtonpost.com/dr-yuval-noah-harari/inequality-rich-superior-biological_b_5846794.html">a genetically stratified society</a>. </p>
<p>These objections, though, would also apply to somatic therapy. Modification of the genes in only certain cells is nevertheless still tinkering with human nature, attempting to bring about a superior genetic profile in a person. If one supports a moratorium for germline therapies on such grounds, one should also support a moratorium on somatic therapies, on similar grounds.</p>
<p>As a bioethicist, I suggest we apply the same regulatory approach to somatic gene therapy as to germline therapy. Given the much stronger evidence for the safety and efficacy of certain somatic therapies, in the near-term this will likely mean offering clinical somatic therapies and not clinical germline therapies. Or we could ban both, if one seriously objects to playing God with the human genome.</p>
<p>But carving out a separate regulatory category, as the committee statement seems to imply, is not justified.</p><img src="https://counter.theconversation.com/content/51843/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>G. Owen Schaefer does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The International Summit on Human Gene Editing drew a distinction between editing an individual’s body cells and editing germline cells that would pass changes to future generations. Does that make sense?G. Owen Schaefer, Research Fellow in Biomedical Ethics, National University of SingaporeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/514892015-12-03T18:52:53Z2015-12-03T18:52:53ZGene editing could open up animal organ transplants into humans<figure><img src="https://images.theconversation.com/files/103988/original/image-20151202-14432-1nthixl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The cultivation of pig organs for human transplantation carries great risk and promise.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/cafnr/14205076730/in/photolist-nDfJq3-77pp74-HMLwA-8vyGek-6jajSA-9cV7vn-w89uxS-wp4YS5-aFckNP-wqernV-wqefbX-w89FsN-6K7Wbk-5ja3od-6KFLvQ-w89GBy-wp5PBu-5UANa9-5fC17g-oeL9wM-nVBSHj-nDfmGx-nDfmwn-77aYyR-h3VdS2-bKVUtR-wpL5Ge-wpKos6-6TAgjG-drdR6K-adykrD-aFfqjY-p84WyW-aFgcNw-bsWSt-xw5rVs-dre18N-fvfie6-fvuzp1-p84oSb-aFg89w-oeKZfS-cyKeqy-oKie3d-6A6uEJ-nDfvcC-3wCZdT-wiSmqB-7rwmuE-5dF49U">CAFNR/flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span></figcaption></figure><p>The clinical potential and ethical difficulty posed by gene-editing technology, which can “find and replace” targeted genes, is <a href="http://www.sciencemag.org/content/346/6213/1258096?intcmp=collection-crispr">seemingly endless</a>. </p>
<p>But while public attention is focused on whether we should use it to change the genes of embryos, application of the technology to genetically modify pig tissues and organs for transplantation into humans could potentially have a bigger and more immediate impact on human health.</p>
<p>The transplantation of living cells, tissues, or organs from one species to another is known as <a href="http://www.ncbi.nlm.nih.gov/pubmed/22019026">xenotransplantation</a>. It has long been championed as a solution to the shortage of human donor organs. Xenotransplantation could be used either as definitive therapy or to “buy time” while the patient waits for a human donor organ. </p>
<p>While progress has been slow, <a href="http://www.ncbi.nlm.nih.gov/pubmed/25386833">trials</a> have demonstrated benefit in patients with type 1 diabetes who are transplanted with porcine pancreatic cells. And <a href="http://www.sciencemag.org/content/350/6264/1101.abstract">gene-editing research published in October</a> shows incredible promise for making xenotransplantation a reality.</p>
<h2>The challenges of xenotransplantation</h2>
<p>Xenotransplantation faces two major challenges: the risk of immune rejection and the risk of transmitting diseases from animals to humans (xenozoonosis). </p>
<p>Immune rejection of transplants among humans can be mitigated by carefully matching donor and recipient. But it’s all much more difficult in the case of humans and pigs. The genetic divide means the human immune system is primed to recognise the pig graft as foreign and to attack it. </p>
<p>In terms of xenozoonosis, of particular concern are porcine <a href="https://en.wikipedia.org/wiki/Endogenous_retrovirus">endogenous retroviruses</a>. These are found in the pig genome and cannot be eliminated by bio-secure breeding. If these retroviruses become activated, they can cause serious infection in human hosts. </p>
<p>While no cases of such infections have been recorded in human recipients of porcine grafts, these viruses have been shown to <a href="http://www.nature.com/nm/journal/v3/n3/abs/nm0397-282.html">infect human cells in vitro</a>.</p>
<p>Scientists have explored a <a href="http://www.ncbi.nlm.nih.gov/pubmed/19566656">range of strategies</a> – either reducing or suppressing the expression of porcine endogenous retroviruses in pig tissue – <a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0122059">to mitigate the risk</a> of transmission to humans. But these have limited efficiency and are costly. </p>
<p>“Find and replace” gene editing (CRISPR/Cas9), in contrast, appears to provide real promise. </p>
<p><a href="http://www.sciencemag.org/content/350/6264/1101.abstract">Scientists from Harvard University</a> have used the technology to target and inactivate porcine endogenous retroviruses in the genome of pig kidney cells. They showed more than a 1,000-fold reduction of viral transmission to human cells in vitro. </p>
<p>The researchers managed to target genes that sit on the surface of porcine cells, which are known to trigger a human immune response. Their work shows genuine possibility for porcine tissues and organs being modified and transplanted into humans without the need for immunosuppressant medication and with little risk of porcine endogenous retrovirus transmission.</p>
<h2>Scientific challenges and ethical concerns</h2>
<p>But the gene-editing technology the Harvard scientists used is not without problems. A number of <a href="https://theconversation.com/gene-editing-in-embryos-is-fraught-with-scientific-and-ethical-issues-51476">scientific challenges and ethical concerns</a> remain. </p>
<p>Foremost is the uncertain safety profile of CRISPR/Cas9 gene editing. While the scientists found the technology didn’t cause any unintended mutations in the porcine genome, its use in non-viable human embryos <a href="http://link.springer.com/article/10.1007%2Fs13238-015-0153-5">has been reported</a> to split DNA segments at sites that weren’t targeted. This raises the possibility it <a href="http://genome.cshlp.org/content/early/2013/11/12/gr.162339.113">may cause mutations that could lead to cancer</a>.</p>
<p>One of the great challenges of xenotransplantation is that pathogens occurring in the organ may be unknown. While the risk of xenozoonoses due to unknown pathogens is low, the potential risks are profound. And we should avoid scientific hubris in our enthusiasm for exploring the implications of this technology for xenotransplantation.</p>
<p>The technology also raises biosecurity and regulatory concerns, because in contrast with traditional gene modification techniques it’s efficient, cheap and simple to apply. As bioscience becomes “democratised”, technologies like CRISPR/Cas9 may be used by individuals or groups outside regulated research environments or with intent to synthesise virulent organisms to inflict harm on others.</p>
<p>The application of CRISPR/Cas9 in transplantation may also increase pressure for it to be used widely, in settings that are currently tightly restricted or controlled. </p>
<p>And the possibility that it could be used to change sperm, egg and embryonic cells, which are known as germline cells, raises the spectre of eugenics and human enhancement for non-medical reasons. This could also lead to trans-generational risks. </p>
<p>While CRISPR/Cas9 may provide the impetus for progress in xenotransplantation that’s been lacking for almost two decades, only if it proceeds in an ethically defensible manner, and with robust regulatory oversight, will it gain widespread public acceptance.</p><img src="https://counter.theconversation.com/content/51489/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>Public attention is focused on whether we should use gene editing technology on embryos, but it could potentially have a bigger and more immediate impact on human health via animal organ donation.Ronald Kam Fai Fung, Research Scholar, Centre for Values, Ethics and the Law in Medicine, University of SydneyIan Kerridge, Associate Professor in Bioethics & Director, Centre for Values and Ethics and the Law in Medicine, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/514742015-12-02T19:29:41Z2015-12-02T19:29:41ZFive reasons we should embrace gene-editing research on human embryos<figure><img src="https://images.theconversation.com/files/104001/original/image-20151202-14464-o2f6h4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Future people would be grateful if their disease is cured, rather than being replaced by a different healthier or non-disabled person.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/40765798@N00/2396559684/">sabianmaggy/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Scientists from around the world are <a href="http://www.nationalacademies.org/gene-editing/index.htm">meeting in Washington this week to debate</a> how best to proceed with research into gene-editing technology. </p>
<p><a href="https://theconversation.com/explainer-crispr-technology-brings-precise-genetic-editing-and-raises-ethical-questions-39219">Gene editing</a> is a new precise form of genetic engineering. It uses enzymes from bacteria to locate genes within DNA and delete or replace them. In early 2015, Chinese scientists used it <a href="http://www.ncbi.nlm.nih.gov/pubmed/25894090">to modify human embryos</a> as a first step towards preventing the genetic transmission of a blood disease. </p>
<p>Many people, including scientists, are worried about creating genetically modified humans. They’re worried about numerous things: genetic mistakes being passed on to the next generation; the creation of designer babies who are more intelligent, more beautiful or more athletic; and the possibility of causing severe growth abnormalities or cancer.</p>
<p>While these are <a href="https://theconversation.com/why-we-can-trust-scientists-with-the-power-of-new-gene-editing-technology-51480">valid concerns</a>, they don’t justify a ban on research. Indeed, such research is a moral imperative for five reasons.</p>
<h2>1. Curing genetic diseases</h2>
<p>Gene editing could be used to cure genetic diseases such cystic fibrosis or thalassaemia (the blood disease that the Chinese researchers were working to eliminate). At present, there are no cures for such diseases. </p>
<p>Detractors say selection of healthy embryos or fetuses via genetic testing is preferable. But such genetic tests require abortion or embryo destruction, which is also objectionable to some people. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/103997/original/image-20151202-14440-wuneo6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/103997/original/image-20151202-14440-wuneo6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=428&fit=crop&dpr=1 600w, https://images.theconversation.com/files/103997/original/image-20151202-14440-wuneo6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=428&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/103997/original/image-20151202-14440-wuneo6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=428&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/103997/original/image-20151202-14440-wuneo6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=538&fit=crop&dpr=1 754w, https://images.theconversation.com/files/103997/original/image-20151202-14440-wuneo6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=538&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/103997/original/image-20151202-14440-wuneo6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=538&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Gene-edited embryonic stem cell lines that cause or protect against disease could help us understand the origins of disease.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/11304375@N07/6867005898/">Image Editor/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
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<p>What’s more, genetic selection doesn’t benefit patients - it’s not a cure. It merely brings a different person, who is free from disease, into existence. Future people would be grateful if their disease is cured, rather than being replaced by a different healthier or non-disabled person.</p>
<h2>2. Dealing with complex diseases</h2>
<p>Most common human diseases, such as heart disease or schizophrenia, don’t just involve one gene that’s abnormal (such as in cystic fibrosis). They’re the result of many, sometimes hundreds, of genes combining to cause ill health. </p>
<p>Genetic selection technologies can’t eliminate genetic predispositions to these diseases. In principle, gene editing could be used to reduce the risk of heart disease or Alzheimer’s disease.</p>
<h2>3. Delaying or stopping ageing</h2>
<p>Each day, thousands of people die from age-related causes. Cardiovascular disease (strongly age-related) is emerging as the biggest cause of death in the developing world. Ageing kills 30 million every year. </p>
<p>That makes it the most under-researched cause of death and suffering relative to its significance. Indeed, age-related diseases, such as heart disease or cancer, are really the symptoms of an underlying disease: ageing.</p>
<p>Gene editing could delay or arrest ageing; this has already been achieved in mice. Gene editing might offer the prospect of humans living twice as long, or perhaps even hundreds of years, without loss of memory, frailty or impotence.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/103996/original/image-20151202-14464-ovh5mb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/103996/original/image-20151202-14464-ovh5mb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=461&fit=crop&dpr=1 600w, https://images.theconversation.com/files/103996/original/image-20151202-14464-ovh5mb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=461&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/103996/original/image-20151202-14464-ovh5mb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=461&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/103996/original/image-20151202-14464-ovh5mb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=580&fit=crop&dpr=1 754w, https://images.theconversation.com/files/103996/original/image-20151202-14464-ovh5mb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=580&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/103996/original/image-20151202-14464-ovh5mb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=580&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Age-related diseases, such as heart disease or cancer, are really the symptoms of an underlying disease: ageing.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/neilmoralee/15680209728/">Neil Moralee/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
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<h2>4. Stopping the genetic lottery</h2>
<p>The fourth reason for supporting gene-editing research on human embryos is the flip side of the designer baby objection. People worry that such technology could be used to create a master race, like fair-haired, blue-eyed “Aryans”. </p>
<p>What this concern neglects is that the biological lottery – i.e. nature – has no mind to fairness. Some are born gifted and talented, others with short painful lives or severe disabilities. While we may worry about the creation of a genetic masterclass, we should also be concerned about those who draw the short genetic straw. </p>
<p>Diet, education, special services and other social interventions are used to correct natural inequality. Ritalin, for example, is prescribed to up to 10% of children with poor self-control to improve their educational prospects and behavioural control. </p>
<p>Gene editing could be used as a part of public health care for egalitarian reasons: to benefit the worst off. People worry that such technologies will be used to benefit only those who can afford it – keep reading for why they shouldn’t.</p>
<h2>5. Making disease treatments less costly</h2>
<p>Gene editing of human embryos could enable greater understanding of disease and new treatments that don’t modify human beings.</p>
<p>Gene-edited embryonic stem cell lines that cause or protect against disease could help us understand the origins of disease. Other edited stem cells could help treatment - imagine blood cells that kill and replace leukemic cells. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/103995/original/image-20151202-14461-lig1aq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/103995/original/image-20151202-14461-lig1aq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/103995/original/image-20151202-14461-lig1aq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/103995/original/image-20151202-14461-lig1aq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/103995/original/image-20151202-14461-lig1aq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=504&fit=crop&dpr=1 754w, https://images.theconversation.com/files/103995/original/image-20151202-14461-lig1aq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=504&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/103995/original/image-20151202-14461-lig1aq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=504&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Concerns about gene-editing technology being used to create designer babies neglects that the biological lottery - or nature - has no mind to fairness.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/booleansplit/3856718374/">Robert S. Donovan/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<p>This knowledge could be used to develop treatments for diseases, including drugs, that can be produced cheaply. And that would reduce, rather than increase, inequality.</p>
<h2>The moral imperative</h2>
<p>There are valid concerns about applying gene editing to create live born babies. Such reproductive applications could be banned. </p>
<p>But the technology could be used for therapeutic research: to understand disease and develop new treatments. And any constraints we place on it must keep this in mind. </p>
<p>Laws to prevent reproductive gene editing may be justified on the basis of safety concerns but a ban on therapeutic gene editing cannot.</p>
<p>To ban it would be to ignore a great deal of good that can be done for a great many people, including some of the most vulnerable.</p><img src="https://counter.theconversation.com/content/51474/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Julian Savulescu 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>Experts from around the world are in the US to discuss the scientific, ethical and governance issues linked to human gene editing. Here are five reasons they shouldn’t ban research in the field.Julian Savulescu, Sir Louis Matheson Distinguishing Visiting Professor at Monash University, Uehiro Professor of Practical Ethics, University of OxfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/514832015-12-02T19:29:31Z2015-12-02T19:29:31ZDebate on whether we should use gene-editing technology is far from black and white<figure><img src="https://images.theconversation.com/files/104034/original/image-20151202-14470-1mdbtql.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The real question is not whether gene editing should be allowed or banned, but how it should be regulated.</span> <span class="attribution"><span class="source">shutterstock</span></span></figcaption></figure><p>Arguments in favour of embracing gene editing focus on how it can deliver <a href="http://theconversation.com/five-reasons-we-should-embrace-gene-editing-research-on-human-embryos-51474">cheap treatments and cures</a> for some truly awful medical conditions. They contest banning the technology based on all the good it can do for people, especially the most vulnerable. </p>
<p>Diseases are bad, cures are great, and gene editing may indeed deliver those cures. Who wouldn’t agree with that? Indeed, who in their right minds would forgo such a great deal of good? </p>
<p>It’s hard to argue with any of this. But although we share these sentiments, we think it’s unhelpful to frame this as a debate about whether to allow or to ban gene editing.</p>
<h2>A false and unhelpful dichotomy</h2>
<p>Debates about the regulation of emerging technologies are often presented in polarised terms. </p>
<p>Consider smart drugs: when the question posed is <a href="http://intelligencesquaredus.org/iq2-tv/item/1471-college-students-should-be-allowed-to-take-smart-drugs">whether students should be allowed to use smart drugs</a>, it’s hard to see anything other than two options. </p>
<p>Either we embrace the technology with arms wide open and hope for the best – that the benefits will outweigh the costs – or we prohibit it, banish it and forgo all those benefits. Tough choice. Should it be banned or should it be allowed? </p>
<p>When the question is posed this way it invites <a href="http://www.bostonglobe.com/opinion/2015/07/31/the-moral-imperative-for-bioethics/JmEkoyzlTAu9oQV76JrK9N/story.html">false dichotomies</a> that present only a choice between the paralysis of the precautionary principle (when unsure, do nothing) and the reckless embrace of new technologies unaided by safety nets should things go awry. </p>
<p>Thankfully, though, the landscape of regulation is much more interesting and textured. Making this texture explicit avoids the unhelpful dichotomy and opens up opportunities for useful regulatory responses.</p>
<h2>How to regulate</h2>
<p>The real question is not whether gene editing – or smart drugs, or any other emerging technology for that matter – should be allowed or banned, but how it should be regulated. </p>
<p>First, prohibition and permission are just two modes of regulation on a scale that includes at least the following: prohibit; discourage; permit; encourage; require. Why, then, limit ourselves to allowing or prohibiting when we could require, encourage or discourage? </p>
<p>Second, precisely <em>who</em> should be permitted – or encouraged, required, discouraged, or prohibited? Are we talking about scientists, physicians or the public here? </p>
<p>Might we not require – at least for a while – scientists to conduct research into gene editing technologies, while prohibiting everyone else from doing likewise? </p>
<p>Might different kinds of regulation not apply to what goes on in research laboratories, in doctors’ offices and in the privacy of people’s homes?</p>
<p>Third, who should do the permitting, encouraging, requiring, discouraging or prohibiting? Government technocrats? Scientific organisations? Corporations that market gene editing technologies? Citizens via referenda? </p>
<p>The reason this matters is that nobody likes to be told what they can and cannot do by someone else. When the question is posed in terms of “should you be allowed to X?”, where X is something you might want, it’s hard to reply in any other way than: “Of course I should be allowed! I can make my own decision, thank you very much.” </p>
<p>What this debate’s really about is how you, and others like you, would like this technology to be used by people like you. It’s a debate about who should regulate whom in what way.</p>
<h2>Why regulate that way</h2>
<p>It’s also a debate about why and when. What criteria should be used to make the above regulatory decisions, and how often should we re-visit them? </p>
<p><a href="http://theconversation.com/five-reasons-we-should-embrace-gene-editing-research-on-human-embryos-51474">Others</a> have mentioned distinctly medical and bioethics-related criteria that speak of diseases, treatments, cures, safety, effectiveness, risks and costs. Notice, though, that framing the discussion in this manner predicates the use of gene-editing technology on whether something is called a “disease”.</p>
<p>But what is and is not a medical condition is itself a terribly murky question. We worry that this debate will only become murkier if we make therapy a condition of legitimate use of gene editing. </p>
<p>It also implicitly excludes a range of other non-bioethics factors from consideration. Some reasons for regulating emerging technologies might have little or nothing to do with medicine and everything to do with how we wish to live our lives. This is not because another way to live our lives would be medically advisable, but because we prefer to live in a different way.</p>
<p>And regardless of what regulatory decisions we make right now, might we not want to revisit this question some time later down the track? After we’ve learned from our experiences, to adjust how we regulate the emerging technology?</p>
<h2>The heart of the matter</h2>
<p>Gene editing is a powerful technology. But it’s unhelpful to discuss its pros and cons in terms of whether we should allow or prohibit it. And whether it is medically justified or not.</p>
<p>The real questions are far more subtle and interesting: who should regulate whose use and in what way? What are good grounds for regulating it in those ways? And how could we design our regulatory regimes in such a way as to ensure that some time down the track, perhaps once we’ve had a chance to experiment with the technology, we still have the option to back out, or to embrace it more fully or in another way?</p>
<p>This is a debate within political philosophy and the philosophy of technology. It’s not just a debate within bioethics, and it’s definitely worth keeping a broad view of it.</p><img src="https://counter.theconversation.com/content/51483/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Nicole A Vincent's work on this topic was made possible through the support of a grant from the John Templeton Foundation, via The Enhancing Life Project. The opinions expressed in this publication are those of the author(s) and do not necessarily reflect the views of the John Templeton Foundation.</span></em></p><p class="fine-print"><em><span>Emma A. Jane does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The debate about regulating gene editing technology is often couched in polar terms, but understanding degrees of regulation that might be a better approach.Nicole A Vincent, Associate Professor of Philosophy, Law, and Neuroscience, Georgia State UniversityEmma A. Jane, Senior Lecturer in Media, Journalism and Communication, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/514802015-12-01T19:15:45Z2015-12-01T19:15:45ZWhy we can trust scientists with the power of new gene-editing technology<figure><img src="https://images.theconversation.com/files/103829/original/image-20151201-26546-ofjsvn.png?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Gene editing allows us to eliminate any misspellings, introduce beneficial natural variants, or perhaps cut out or insert new genes. </span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/libertasacademica/7016004213/">Libertas Academica/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p><a href="http://www.nationalacademies.org/gene-editing/index.htm">A summit of experts</a> from around the world is meeting in Washington to consider the scientific, ethical and governance issues linked to research into gene editing. Convened in response to recent advances in the field, the summit includes experts from the US National Academy of Science, the UK’s Royal Society and the Chinese Academy of Science. </p>
<p><a href="https://theconversation.com/explainer-what-is-genome-editing-25072">Gene editing</a> is a new technique that allows one to change chosen genes at will. It has been applied to many organisms but <a href="http://www.ncbi.nlm.nih.gov/pubmed/25894090">a recent report</a> from China showing the modification of human embryos using a technology known as <a href="https://theconversation.com/explainer-crispr-technology-brings-precise-genetic-editing-and-raises-ethical-questions-39219">CRISPR/Cas9</a> mediated editing set alarm bells ringing. </p>
<p>Here’s the main fear: if you modify an embryo (and therefore also its germline), you change not only the person that embryo will become but also its future sons, daughters, grandsons and granddaughters. </p>
<p>Since we don’t know much about this technology, it’s right to stop and think about it. But personally I’m not overly concerned: we’ve been here – or somewhere quite like it – before. </p>
<h2>Learning from history</h2>
<p>In 1975, scientists met at Asilomar on the Californian coast to discuss a moratorium on recombinant DNA (that’s DNA formed from combining constituents from different organisms). </p>
<p>Alarm bells had started ringing when scientists realised they could combine the DNA from a monkey virus with a circle of DNA called a plasmid, carrying an antibiotic resistance gene purified from the human gut bacteria, <em>Escherichia coli</em> (<a href="http://www.about-ecoli.com/"><em>E. coli</em></a>). </p>
<p>This cocktail sounded dangerous and scientists discussed a voluntary moratorium on certain experiments, as well as sensible guidelines for containing recombinant material within laboratories. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/103830/original/image-20151201-26578-1n37bah.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/103830/original/image-20151201-26578-1n37bah.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/103830/original/image-20151201-26578-1n37bah.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/103830/original/image-20151201-26578-1n37bah.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/103830/original/image-20151201-26578-1n37bah.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/103830/original/image-20151201-26578-1n37bah.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/103830/original/image-20151201-26578-1n37bah.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Horizontal gene transfer occurs in nature when DNA is carried between species by viruses and related carriers.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/blprnt/3694704325/">Jer Thorp/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<p>Regulations and guidelines are still in place and after 40 years few, if anyone, has been harmed by recombinant DNA. And there have been no reported outbreaks of recombinant material that have significantly affected human health or the environment. </p>
<p>All technologies, including different agricultural practices, have upsides and downsides, and most medicines and treatments have side effects. But recombinant DNA would now have to be classed among the least dangerous of scientific developments.</p>
<h2>Understanding science</h2>
<p>One reason the technology has proven so safe may be that genetic recombination has been going on for millions of years. In most cases, genes are simply passed on from parent to child. But horizontal gene transfer also occurs in nature when DNA is carried between organisms or even species by viruses. </p>
<p>Over time, DNA is naturally swapped around and moved. Though you may have eaten transgenic plant products, I very much doubt you’ve noticed.</p>
<p>There was a fear “mad scientists” would invent dangerous new superbugs and killer viruses. Perhaps this could have happened, but sadly there are enough pre-existing dangerous substances and naturally occurring diseases, which have been perfected by evolution, out there already. So germ warfare scientists are more likely to just use them.</p>
<p>Another fear was that researchers would modify humans. Most countries quickly outlawed the modification of human germ cells and, to my knowledge, it has never occurred. In general, scientists seem to have obeyed the regulations. </p>
<p>But another reason is that it has proved difficult to introduce new genes into mammalian cells. It’s legal to modify human cells, such as blood stem cells, to cure genetic diseases. But human cells are among the hardest to modify. Human “anti-viral” software seems so powerful that it inhibits the stable insertion and expression of new DNA.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/103831/original/image-20151201-26595-n1zvf7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/103831/original/image-20151201-26595-n1zvf7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=426&fit=crop&dpr=1 600w, https://images.theconversation.com/files/103831/original/image-20151201-26595-n1zvf7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=426&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/103831/original/image-20151201-26595-n1zvf7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=426&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/103831/original/image-20151201-26595-n1zvf7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=536&fit=crop&dpr=1 754w, https://images.theconversation.com/files/103831/original/image-20151201-26595-n1zvf7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=536&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/103831/original/image-20151201-26595-n1zvf7.jpg?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">
<figcaption>
<span class="caption">Fears that ‘mad scientists’ would use recombinant DNA techonolgy to create superbugs like MRSA have not eventuated.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/umdnews/8161119599/in/photolist-draSwB-bhhrmR-ibEmCY-6VESwi-kGq5r8-4BwtJZ-4BAEnC-4BACiY-pBtfyG-cNTZNU-cNTZH1-cPsbUS-nVzYss-cPsc4Y-cPsbTm-cPsc1u-dV5XkT-csnK1o-csnJwo-csnJzY-csnJum-crj1db-dMgueE-5QXCmd-dMaV1V-ddaJBA-r4TfX3-csnJBs-f37psU-csnJKy-csnJG1-f3SzQs-dNZC2S-7bepH7-2Mxz5W-dNZBuf-csnJLU-csnJXj-ekEQAg-csnJNm-csnJHY-7biLPL-dNZBwm-edsrB8-e29y8j-dZtRxo-dZo9rR-dZo9bv-dZtQGW-dZtQhf">Merrill College of Journalism Press Releases</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<h2>The promise of gene editing</h2>
<p>I’m sure you’ve met people who’ve had their teeth straightened or undergone cosmetic surgery. But you’ve probably never met anyone who’s had gene therapy or ever seen a transgenic animal.</p>
<p>Could that change with gene editing? Gene editing is so precise that one doesn’t just lob in a new gene and hope it works; what one does is edit the existing gene to eliminate any misspellings, introduce beneficial natural variants, or perhaps cut out or insert new genes into chosen locations. </p>
<p>Our anti-viral software may not even detect what’s happened. And provided there aren’t any “off-target’” effects, where we hit the wrong gene, there may be no or minimal side effects.</p>
<p>Now that’s it’s so easy to meddle in human genes, why shouldn’t we worry? </p>
<p>The new technology is a game-changer – but it’s not a runaway phenomenon, like releasing cane toads, blackberries or rabbits into Australia. After 40 years, there have been few, if any problems, with genetically modified organisms. And the experiments - though much easier now - are still so elaborate and expensive that the technology will spread slowly. </p>
<p>We’ll likely remain cautious about modifying human embryos and about any modification that may be passed on to the next generation. To date, consent is required for all treatments. And while patients may opt for experimental cancer therapy or surgery, we always try to think carefully when others, who cannot consent, will be affected.</p>
<p>Some people will even ask why it’s wrong to correct a defect that could haunt future generations. Or, if we could introduce a gene variant that protects people from cancer – such as creating a duplication of the <a href="http://www.ncbi.nlm.nih.gov/books/NBK22268/">tumour suppressor gene p53</a> – why wouldn’t we want that for our children?</p>
<p>Genetics is a branch of science that’s ripe for discussions, and conversations on recombinant DNA, gene therapy, cloning and stem cells have all gone well. Guidelines have been sensible and researchers have largely complied with them. </p>
<p>The very fact that people from across the world are gathering to discuss the issues surrounding the latest breakthroughs in gene technology is a very strong sign that the science will be used responsibly. One hopes that the concurrent meeting on climate change in Paris is also a victory for science.</p><img src="https://counter.theconversation.com/content/51480/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Merlin Crossley works for the University of New South Wales. He receives funding from the National Health and Medical Research Council and the Australian Research Council. He is a Trustee of the Australian Museum, a Board Member of the Sydney Institute of Marine Science, a Council Member of the European Molecular Biology Laboratory Australia, and the Australian Science Media Centre.</span></em></p>Should the gathering of experts from around the world that’s considering the scientific, ethical, and governance issues linked to research into gene editing ring alarm bells?Merlin Crossley, Dean of Science and Professor of Molecular Biology, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/514762015-12-01T19:13:14Z2015-12-01T19:13:14ZGene editing in embryos is fraught with scientific and ethical issues<figure><img src="https://images.theconversation.com/files/103840/original/image-20151201-26549-tgy4q1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Genetic changes to embryos will not only affect the person that embryo becomes but also all their descendants.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/anniferrr/5190095551/">anna gutermuth/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span></figcaption></figure><p>Recent technological advances have revolutionised our ability to manipulate the genetic code, allowing us to specifically edit individual genes. Gene editing offers exciting potential for disease therapies but application of the technology in embryos also raises many ethical and scientific issues.</p>
<p>Humans - and all other mammals - reproduce through sperm and eggs (germ cells) that transmit a single copy of each parent’s chromosomes to the offspring. When an embryo forms at conception, it has a mix of genes from both germs cells, producing a child who’s a biological reflection of the parents.</p>
<p>Sometimes, harmful mutations or changes in a gene sequence are transmitted by the germ cells and have deleterious effects in the embryo or in later life. In recent decades, genetic screening has allowed detection of particular genetic aberrations in early embryos. This has allowed us to avoid some of the harmful consequences of specific damaging mutations through pregnancy termination. </p>
<p>While genetic screening poses complex ethical questions, it’s safe and doesn’t introduce changes to genes that affect the baby or the baby’s future children. By contrast, gene editing affects both.</p>
<h2>Risking off-target effects</h2>
<p>Gene-editing technologies have introduced the possibility of altering individual genes in eggs or sperm, or immediately after fertilisation in the earliest human embryos. This has the potential to correct gene mutations that underlie inherited disease. </p>
<p>But such germline gene therapy doesn’t only affect the individual germ cells or embryo that has been treated; any changes will be transmitted to the future children of that individual. </p>
<p>This is highly controversial as it raises major safety concerns and the spectre of introducing “designer” mutations, in which specific genetic traits could be modified according to parents’ requirements. </p>
<p>Clearly, there are fundamental social and ethical considerations involved that preclude the use of gene editing in the human germline or in human embryos. But critical questions also surround safety and the potential biological impacts of gene editing if it were to be applied in humans.</p>
<p>The most obvious risk of editing embryo genes is the potential for errors or of introducing off-target genetic effects. Off-target effects occur when gene technology mistakenly hits a DNA sequence that’s not the intended target. </p>
<p>While gene editing can be very specific, even minor errors or off-target effects are unacceptable in human embryos as they could harm the developing fetus or cause disease in adulthood. Off-target sites can also include the surprisingly large proportion of DNA sequence that lies between genes and plays important roles in gene regulation. </p>
<p>Critically, changes to any of these sequences will then be inherited by future generations.</p>
<h2>The epigenetic black box</h2>
<p>Other concerns surround potential effects on the way genes are regulated in the embryo. Although we’ve made unprecedented advances in biotechnology, we’re only beginning to understand the complex biological systems that regulate fetal formation and influence lifelong health. </p>
<p>While gene sequence is paramount, additional information provided around the DNA is also crucial for development. One such example is the epigenetic code, which controls whether the thousands of genes contained in each cell are switched on and off in the correct combination, in the correct tissue, over a lifetime. </p>
<p>Epigenetic information contained in each cell type is passed to each new cell as it divides to maintain or renew each tissue. This code ensures the long-term identity of cell types and the proper function of the tissue and organs they constitute. </p>
<p>Two important epigenetic issues arise in the context of editing embryo genes. First, environmental stimuli, such as chemicals, drugs or even diet, can alter epigenetic mechanisms. Second, disruptions in this code can lead to disease, a concept that is best illustrated in cancer development. </p>
<p>Importantly, both the sperm and egg transmit epigenetic information to the newly fertilised embryo. This epigenetic information affects development, health and even behaviour in the offspring. </p>
<p>Growing evidence indicates certain environmental stimuli alter epigenetic state in the germline and significantly affect outcomes not only in children, but also in grandchildren. Despite this, we have little understanding of how these effects are mediated in the developing embryo.</p>
<h2>Cause for caution</h2>
<p>While gene editing may be designed to correct a very specific genetic mutation, the change must be made in an embryo culture environment – that is, in the lab. Although embryo culture conditions are carefully controlled, we still have no way of properly measuring the potentially complex impacts of the gene-editing process on the embryo</p>
<p>Importantly, any negative effects may not be limited to the actual edit; they may also result from the gene-editing process, which requires the use of specific enzymes, chemicals and reagents in an artificial culture environment. These too may alter epigenetic state and other mechanisms in the embryo. </p>
<p>Despite the rapid progress and undeniable power of gene-editing technologies, we’re still in the early stages of understanding the impacts of these processes on the genetic and epigenetic state of embryos and the future health and development of the person they become. The ethical issues surrounding germline gene therapy in humans are also enormous (more on that in The Conversation tomorrow). </p>
<p>If such technology were ever to be applied to the human germline for medical purposes, these issues would need to be addressed with the greatest stringency.</p><img src="https://counter.theconversation.com/content/51476/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Patrick Western receives funding from the National Health and Medical Research Council of Australia. </span></em></p>While gene editing offers the exciting potential for disease therapies, using it on human embryos opens up a can of worms.Patrick Western, Research Group Head, Germ Cell Development and Epigenetics, Hudson InstituteLicensed as Creative Commons – attribution, no derivatives.