tag:theconversation.com,2011:/us/topics/human-gene-editing-63071/articlesHuman gene editing – The Conversation2024-03-27T19:07:40Ztag:theconversation.com,2011:article/2263932024-03-27T19:07:40Z2024-03-27T19:07:40ZThe first pig kidney has been transplanted into a living person. But we’re still a long way from solving organ shortages<figure><img src="https://images.theconversation.com/files/584634/original/file-20240327-22-zkx0ie.jpg?ixlib=rb-1.1.0&rect=0%2C73%2C8192%2C5383&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.massgeneral.org/news/press-release/worlds-first-genetically-edited-pig-kidney-transplant-into-living-recipient">Massachusetts General Hospital</a></span></figcaption></figure><p>In a world first, we heard last week that US surgeons had transplanted a kidney from a gene-edited pig into a living human. News reports said the procedure was <a href="https://www.npr.org/sections/health-shots/2024/03/21/1239790816/first-pig-kidney-human-transplant">a breakthrough</a> in xenotransplantation – when an organ, cells or tissues are transplanted from one species to another.</p>
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<figcaption><span class="caption">The world’s first transplant of a gene-edited pig kidney into a live human was announced last week.</span></figcaption>
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<p>Champions of xenotransplantation regard it as <em>the</em> solution to organ shortages across the world. In December 2023, <a href="https://www.anzdata.org.au/anzod/publications-2/organ-waiting-list/">1,445 people</a> in Australia were on the waiting list for donor kidneys. In the United States, more than <a href="https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/">89,000</a> are waiting for kidneys. </p>
<p>One biotech CEO says gene-edited pigs <a href="https://www.technologyreview.com/2015/08/12/248193/surgeons-smash-records-with-pig-to-primate-organ-transplants/">promise</a> “an unlimited supply of transplantable organs”.</p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6452271/">Not</a>, <a href="https://theconversation.com/organ-transplants-from-pigs-medical-miracle-or-pandemic-in-the-making-175290">everyone</a>, though, <a href="https://onlinelibrary.wiley.com/doi/10.1111/imj.13183">is convinced</a> transplanting animal organs into humans is really the answer to organ shortages, or even if it’s right to use organs from other animals this way.</p>
<p>There are two critical barriers to the procedure’s success: organ rejection and the transmission of <a href="https://journals.sagepub.com/doi/epdf/10.1177/09636897241226849">animal viruses to recipients</a>. </p>
<p>But in the past decade, a new platform and technique known as CRISPR/Cas9 – often shortened to CRISPR – has promised to mitigate these issues.</p>
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Read more:
<a href="https://theconversation.com/organ-transplants-from-pigs-medical-miracle-or-pandemic-in-the-making-175290">Organ transplants from pigs: Medical miracle or pandemic in the making?</a>
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<h2>What is CRISPR?</h2>
<p>CRISPR gene editing takes advantage of a system already found in nature. CRISPR’s “genetic scissors” evolved in bacteria and other microbes to help them fend off viruses. Their cellular machinery <a href="https://www.sciencedirect.com/science/article/pii/S0300908415001042#:%7E:text=The%20system%2C%20called%20CRISPR%2DCas,remember%2C%20recognize%20and%20clear%20infections.">allows them</a> to integrate and ultimately destroy viral DNA by cutting it.</p>
<p>In 2012, two teams of scientists <a href="https://www.science.org/doi/10.1126/science.1225829">discovered how to harness</a> this bacterial immune system. This is made up of repeating arrays of DNA and associated proteins, known as “Cas” (CRISPR-associated) proteins. </p>
<p>When they used a particular Cas protein (Cas9) with a “guide RNA” made up of a singular molecule, they found they could <a href="https://pubmed.ncbi.nlm.nih.gov/22745249/">program</a> the CRISPR/Cas9 complex to break and repair DNA at precise locations as they desired. The system could even “knock in” new genes at the repair site. </p>
<p>In 2020, the two scientists leading these teams were awarded a <a href="https://www.nobelprize.org/prizes/chemistry/2020/summary/">Nobel prize</a> for their work.</p>
<p>In the case of the latest xenotransplantation, CRISPR technology was used to <a href="https://www.massgeneral.org/news/press-release/worlds-first-genetically-edited-pig-kidney-transplant-into-living-recipient">edit 69 genes</a> in the donor pig to inactivate viral genes, “humanise” the pig with human genes, and knock out harmful pig genes.</p>
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<figcaption><span class="caption">How does CRISPR work?</span></figcaption>
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Read more:
<a href="https://theconversation.com/what-is-crispr-the-gene-editing-technology-that-won-the-chemistry-nobel-prize-147695">What is CRISPR, the gene editing technology that won the Chemistry Nobel prize?</a>
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<h2>A busy time for gene-edited xenotransplantation</h2>
<p>While CRISPR editing has brought new hope to the possibility of xenotransplantation, even recent trials show great caution is still warranted.</p>
<p>In 2022 and 2023, two patients with <a href="https://www.medschool.umaryland.edu/news/2023/um-medicine-faculty-scientists-and-clinicians-perform-second-historic-transplant-of-pig-heart-into-patient-with-end-stage-cardiovascular-disease.html#:%7E:text=The%20first%20historic%20surgery%2C%20performed,had%20end%2Dstage%20heart%20disease.">terminal heart diseases</a>, who were ineligible for traditional heart transplants, were granted <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00775-4/abstract">regulatory permission</a> to receive a gene-edited pig heart. These pig hearts had ten genome edits to make them more suitable for transplanting into humans. However, both patients died within several weeks of the procedures. </p>
<p>Earlier this month, we heard a team of surgeons in China transplanted a gene-edited pig liver into a <a href="https://www.nature.com/articles/d41586-024-00853-8">clinically dead man</a> (with family consent). The liver functioned well up until the ten-day limit of the trial.</p>
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Read more:
<a href="https://theconversation.com/you-donate-your-body-to-science-you-die-what-happens-next-1481">You donate your body to science, you die ... what happens next?</a>
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<h2>How is this latest example different?</h2>
<p>The gene-edited pig kidney <a href="https://www.massgeneral.org/news/kidney-xenotransplant-faqs">was transplanted</a> into a relatively young, living, legally competent and consenting adult.</p>
<p>The total number of gene edits edits made to the donor pig is very high. The researchers report making <a href="https://www.nature.com/articles/d41586-024-00879-y">69 edits</a> to inactivate viral genes, “humanise” the pig with human genes, and to knockout harmful pig genes.</p>
<p>Clearly, the race to transform these organs into viable products for transplantation is ramping up.</p>
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Read more:
<a href="https://theconversation.com/what-are-uterus-transplants-who-donates-their-uterus-and-what-are-the-risks-190443">What are uterus transplants? Who donates their uterus? And what are the risks?</a>
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<h2>From biotech dream to clinical reality</h2>
<p>Only a few months ago, CRISPR gene editing made its debut in mainstream medicine. </p>
<p>In November, drug regulators in the <a href="https://www.gov.uk/government/news/mhra-authorises-world-first-gene-therapy-that-aims-to-cure-sickle-cell-disease-and-transfusion-dependent-thalassemia">United Kingdom</a> and <a href="https://www.fda.gov/media/174618/download?attachment">US</a> approved the world’s first CRISPR-based genome-editing therapy for human use – a treatment for life-threatening forms of sickle-cell disease. </p>
<p>The treatment, known as <a href="https://sicklecellanemianews.com/ctx001-sickle-cell-disease">Casgevy</a>, uses CRISPR/Cas-9 to edit the patient’s own blood (bone-marrow) stem cells. By disrupting the <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2029392">unhealthy gene</a> that gives red blood cells their “sickle” shape, the aim is to produce red blood cells with a healthy spherical shape. </p>
<p>Although the treatment uses the patient’s own cells, the same underlying principle applies to recent clinical xenotransplants: unsuitable cellular materials may be edited to make them therapeutically beneficial in the patient.</p>
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<a href="https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Sickle cells have a different shape to healthy round red blood cells" src="https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=337&fit=crop&dpr=1 600w, https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=337&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=337&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">CRISPR technology is aiming to restore diseased red blood cells to their healthy round shape.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-rendered-medical-illustration-sickle-cell-2221001799">Sebastian Kaulitzki/Shutterstock</a></span>
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Read more:
<a href="https://theconversation.com/organs-too-risky-to-donate-may-be-safer-than-we-think-we-crunched-the-numbers-and-heres-what-we-found-124993">Organs 'too risky' to donate may be safer than we think. We crunched the numbers and here's what we found</a>
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<h2>We’ll be talking more about gene-editing</h2>
<p>Medicine and gene technology regulators are increasingly asked to <a href="https://www.utas.edu.au/__data/assets/pdf_file/0011/1634258/OP12-final-report.pdf">approve new experimental trials</a> using gene editing and CRISPR.</p>
<p>However, neither xenotransplantation nor the therapeutic applications of this technology lead to changes to the genome that can be inherited.</p>
<p>For this to occur, CRISPR edits would need to be applied to the cells at the earliest stages of their life, such as to <a href="https://doi.org/10.1089/crispr.2020.0082">early-stage embryonic cells</a> in vitro (in the lab). </p>
<p>In Australia, intentionally creating heritable alterations to the human genome is a criminal offence carrying <a href="https://classic.austlii.edu.au/au/legis/cth/consol_act/pohcfra2002465/s15.html">15 years’ imprisonment</a>. </p>
<p><a href="https://www.utas.edu.au/__data/assets/pdf_file/0011/1634258/OP12-final-report.pdf">No jurisdiction in the world</a> has laws that <a href="https://doi.org/10.1089/crispr.2020.0082">expressly permits</a> heritable human genome editing. However, some <a href="https://crispr-gene-editing-regs-tracker.geneticliteracyproject.org/russia-germline-embryonic/">countries</a> lack specific regulations about the procedure.</p>
<h2>Is this the future?</h2>
<p>Even without creating inheritable gene changes, however, xenotransplantation using CRISPR is in its infancy.</p>
<p>For all the promise of the headlines, there is not yet one example of a stable xenotransplantation in a living human lasting <a href="https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.03060/full">beyond seven months</a>. </p>
<p>While authorisation for this recent US transplant has been granted under the so-called “compassionate use” <a href="https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=312.310">exemption</a>, conventional clinical trials of pig-human xenotransplantation have yet to commence. </p>
<p>But the prospect of such trials would likely require significant improvements in current outcomes to gain regulatory approval <a href="https://www.fda.gov/media/102126/download">in the US</a> or <a href="https://iris.who.int/bitstream/handle/10665/341817/WHO-HTP-EHT-CPR-2011.01-eng.pdf?sequence=1&isAllowed=y">elsewhere</a>. </p>
<p>By the same token, regulatory approval of any “off-the-shelf” xenotransplantation organs, including gene-edited kidneys, would seem <a href="https://link.springer.com/chapter/10.1007/978-981-99-7691-1_24">some way off</a>.</p><img src="https://counter.theconversation.com/content/226393/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Christopher Rudge was a member of a research team that designed and convened an Australian citizens' jury on genome editing in 2021-22. This was funded by the Medical Research Future Fund.</span></em></p>Champions of xenotransplantation see it as the solution to organ shortages across the world. But this technology has other applications.Christopher Rudge, Law lecturer, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1967142022-12-20T17:52:36Z2022-12-20T17:52:36ZDid He Jiankui ‘Make People Better’? Documentary spurs a new look at the case of the first gene-edited babies<figure><img src="https://images.theconversation.com/files/501995/original/file-20221219-14-6lxobo.jpg?ixlib=rb-1.1.0&rect=218%2C11%2C2914%2C2144&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">He Jiankui seemed unprepared for the furor set off by his bombshell announcement.</span> <span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:He_Jiankui.jpg">The He Lab/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>In the four years since an experiment by disgraced scientist He Jiankui resulted in the <a href="https://apnews.com/article/ap-top-news-international-news-ca-state-wire-genetic-frontiers-health-4997bb7aa36c45449b488e19ac83e86d">birth of the first babies with edited genes</a>, numerous articles, books and <a href="https://nap.nationalacademies.org/catalog/25665/heritable-human-genome-editing">international</a> <a href="https://www.who.int/groups/expert-advisory-committee-on-developing-global-standards-for-governance-and-oversight-of-human-genome-editing">commissions</a> have reflected on whether and how heritable genome editing – that is, modifying genes that will be passed on to the next generation – should proceed. They’ve reinforced an international consensus that it’s premature to proceed with heritable genome editing. Yet, concern remains that some individuals might buck that consensus and recklessly forge ahead – just as He Jiankui did.</p>
<p>Some observers – <a href="https://scholar.google.com/citations?user=yebS-LIAAAAJ&hl=en&oi=ao">myself included</a> – have <a href="https://theconversation.com/rogue-science-strikes-again-the-case-of-the-first-gene-edited-babies-107684">characterized He as a rogue</a>. However, the new documentary “<a href="https://makepeoplebetterfilm.com/">Make People Better</a>,” directed by filmmaker Cody Sheehy, leans toward a different narrative. In its telling, He was a misguided centerpiece of a broader ecosystem that subtly and implicitly supported rapid advancement in gene editing and reproductive technologies. That same system threw He under the bus – <a href="https://www.technologyreview.com/2019/12/30/131061/he-jiankui-sentenced-to-three-years-in-prison-for-crispr-babies/">and into prison</a> – when it became evident that the global community strongly rejected his experiments.</p>
<h2>Creation of the ‘CRISPR babies’</h2>
<p>“Make People Better” outlines an already well-documented saga, tracing the path of He from a promising young scientist at Rice and Stanford to a driven researcher establishing a laboratory in China that secretly worked to make heritable genome editing a reality.</p>
<p>He’s experiment involved using the <a href="https://theconversation.com/nobel-prize-for-crispr-honors-two-great-scientists-and-leaves-out-many-others-147730">CRISPR-Cas9 technique</a>. Sometimes compared to “molecular scissors,” this precision tool allows scientists to make very specific edits to DNA in living cells. He used CRISPR to alter the CCR5 gene in human embryos with the goal of conferring immunity to HIV. These embryos were brought to term, resulting in the birth of at <a href="https://www.newscientist.com/article/mg25533930-700-whats-next-for-the-gene-edited-children-from-crispr-trial-in-china/">least three children with altered DNA</a>. </p>
<p>The revelation of the births of the first gene-edited babies in November 2018 resulted in an international uproar. A <a href="https://www.theatlantic.com/science/archive/2018/12/15-worrying-things-about-crispr-babies-scandal/577234/">laundry list</a> of ethical failings in He’s experiment <a href="https://www.nature.com/articles/d41586-018-07573-w">quickly became evident</a>. There was insufficient proof that editing embryos with CRISPR was safe enough to be done in humans. Appropriate regulatory approval had <a href="https://www.scmp.com/news/china/science/article/2182964/china-confirms-gene-edited-babies-blames-scientist-he-jiankui">not been obtained</a>. The parents’ consent was <a href="https://link.springer.com/article/10.1007/s11673-019-09953-x">grossly inadequate</a>. And the whole endeavor was <a href="https://apnews.com/article/health-science-china-medical-ethics-ap-top-news-13303d99c4f849829e98350301e334a9">shrouded in secrecy</a>.</p>
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<figcaption><span class="caption">Trailer for the documentary ‘Make People Better.’</span></figcaption>
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<h2>New context, same story</h2>
<p>Three figures play a central role in “Make People Better”‘s study of He Jiankui. There’s Antonio Regalado, the reporter from MIT Technology Review who broke the original story. There’s Ben Hurlbut, an ethicist and confidante of He. And there’s Ryan (the documentary withholds his full identity), a public relations representative who worked with He to make gene editing palatable to the world. He Jiankui himself was not interviewed, though his voice permeates the documentary in previously unreleased recordings by Hurlbut.</p>
<p>Regalado and Hurlbut have <a href="https://www.technologyreview.com/2019/12/03/75084/nature-jama-rejected-he-jiankui-crispr-baby-lulu-nana-paper/">already</a> <a href="https://doi.org/10.1353/pbm.2020.0013">written</a> a <a href="https://www.technologyreview.com/2019/02/21/137309/the-crispr-twins-had-their-brains-altered/">considerable</a> <a href="https://doi.org/10.1038/d41586-018-07881-1">amount</a> on this saga, so the documentary’s most novel contribution comes from Ryan’s discussion of his public relations work with He. Ryan appears to be a true believer in He’s vision to literally “make people better” by using gene editing to prevent dreadful diseases. </p>
<p>But Ryan is aware that public backlash could torpedo this promising work. His reference point is the initial <a href="https://www.pewresearch.org/science/2015/01/29/public-and-scientists-views-on-science-and-society/">public hostility to GMO foods</a>, and Ryan strove to avoid that outcome by gradually easing the public in to the heritable gene editing experiment.</p>
<p>This strategy turned out to be badly mistaken for a variety of reasons. He Jiankui was himself eager to publicize his work. Meanwhile, Regalado’s <a href="https://www.technologyreview.com/2018/11/25/138962/exclusive-chinese-scientists-are-creating-crispr-babies/">tenacious journalism</a> led him to a clinical trials registry where He had quietly posted about the study.</p>
<p>But ultimately, those factors just affected the timing of revelation. Both Ryan and He failed to appreciate that they had very little ability to influence how the experiment would be received, nor how much condemnation would result.</p>
<h2>Blind spots</h2>
<p>While some documentaries strive to be flies on the wall, objectivity is elusive. Tone, framing, editing and choice of interview subjects all coalesce into a narrative with a perspective on the subject matter. A point of view is not itself objectionable, but it opens the documentary to critiques of its implicit stance.</p>
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<p>An uncomfortable tension lies at the center of “Make People Better.” </p>
<p>On the one hand, the documentary gives substantial attention to Hurlbut and Ryan, who emphasize that He did not act alone. He discussed his plans with <a href="https://doi.org/10.1126/science.365.6452.430">dozens of people</a> in China and around the world, whose implicit support was essential to both the experiment and his confidence that he was doing nothing wrong.</p>
<p>On the other hand, the documentary focuses on understanding He’s background, motives and ultimate fate. Other figures who might have influenced He to take a different path fade into the background – sometimes quite literally, appearing for only seconds before the documentary moves on.</p>
<p>Indeed, as a biomedical ethicist, I believe there is good reason to put responsibility for the debacle squarely on He’s shoulders. Before the news broke in 2018, international panels of experts had already issued <a href="https://www.nationalacademies.org/news/2015/12/on-human-gene-editing-international-summit-statement">advisory statements</a> that heritable gene editing was premature. Individuals like Hurlbut personally advised He as much. The secrecy of the experiment itself is a testament: He must have suspected the international community would reject the experiment if they knew what was going on. </p>
<p>If He had gone through proper, transparent channels – <a href="https://www.cos.io/initiatives/prereg">preregistering the trial</a> and consulting publicly with international experts on his plans before he began – the whole saga could have been averted. He chose a different, more dangerous and secretive path from the vast majority of researchers working in reproductive biotechnology, which I suggest must be acknowledged.</p>
<p>The documentary does not reflect critically on its own title. The origin of the phrase “make people better” is surprising and the film’s most clever narrative moment, so I won’t spoil it. But does heritable gene editing really make people better? <a href="https://doi.org/10.1111/bioe.12878">Perhaps instead</a>, it makes better people. </p>
<p>The gene-edited babies were created via in vitro fertilization specifically as a part of He’s experiment. They would not have existed if He had never gotten involved in gene editing. So, some would argue, He did not save any individual from contracting HIV. Rather, he created new people potentially less likely to contract HIV than the general population. </p>
<p><a href="https://doi.org/10.1007/s11019-020-09947-2">I contend</a> that this doesn’t mean gene editing is pointless. From a population health perspective, gene editing could save lives by reducing the incidence of certain diseases. But this perspective does change the moral tenor of gene editing, perhaps reducing its urgency.</p>
<p>What’s more, editing CCR5 is a dubious means to improve human well-being, since there are already effective ways to prevent HIV infection that are far less risky and uncertain than heritable gene editing. <a href="https://doi.org/10.17226/25665">Scientific consensus suggests</a> that the best first-in-human candidates for heritable gene editing are instead devastating genetic disorders that cannot be ameliorated in other ways.</p>
<h2>The future for He Jiankui</h2>
<p>Perhaps due to the timing of its filming, the documentary does not dwell on He being <a href="https://www.science.org/content/article/chinese-scientist-who-produced-genetically-altered-babies-sentenced-3-years-jail">sentenced to three years in Chinese prison</a> as a result of the experiment, nor mention that <a href="https://www.technologyreview.com/2022/04/04/1048829/he-jiankui-prison-free-crispr-babies/">he was released</a> early in 2022.</p>
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<p>Evidently, He is not content to fade quietly into obscurity. He says he is slated in March 2023 to <a href="https://pandaily.com/chinese-gene-editing-scientist-he-jiankui-sets-up-beijing-lab-following-prison-release/">give a talk at the University of Oxford</a> that may shed more light on his motives and actions. In the meantime, he has <a href="https://www.statnews.com/2022/11/29/after-prison-crispr-babies-scientist-is-attempting-comeback/">established a new biotech start-up</a> focused on developing gene therapies. To be clear, this work does not involve editing embryos.</p>
<p>Still, it appears prison has not diminished He’s ambition. <a href="https://www.scmp.com/news/china/science/article/3201896/chinese-scientist-behind-gene-edited-babies-speak-oxford-university">He claims</a> that he could develop a cure for the degenerative genetic disease Duchenne muscular dystrophy – if he receives funding in excess of US$100 million. </p>
<p>To me, this ambition reflects a curious symmetry between Regalado and He in “Make People Better.” Both are driven to be first, to be at the forefront of their respective fields. Sometimes, as with Regalado, this initiative can be good – his intrepid reporting and instinct to publish quickly brought He’s unethical experiment to a rapid close. But in other cases, like He’s, that drive can lead to dangerous science that runs roughshod over ethics and good governance. </p>
<p>Perhaps, then, the best lesson a viewer can take from “Make People Better” is that ambition is a double-edged sword. In the years to come, it will be up to the international community to keep such ambition in check and ensure proper restrictions and oversight on heritable genome editing.</p><img src="https://counter.theconversation.com/content/196714/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>Scientific and public uproar resulted when the Chinese scientist announced the births of the first human babies with heritable edits to their genes. A new documentary reexamines the saga.G. Owen Schaefer, Assistant Professor in Biomedical Ethics, National University of SingaporeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1553492021-02-19T18:22:46Z2021-02-19T18:22:46ZThe human genome at 20: how biology’s most-hyped breakthrough led to anticlimax and arrests<figure><img src="https://images.theconversation.com/files/385281/original/file-20210219-21-rkb5rg.jpg?ixlib=rb-1.1.0&rect=40%2C0%2C8946%2C5982&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-illustration-virus-dna-molecule-structure-1371386951">Rost9/Shutterstock</a></span></figcaption></figure><p>When President Bill Clinton took to a White House lectern 20 years ago to announce that the <a href="https://home.bt.com/news/on-this-day/june-26-2000-the-book-of-life-falls-open-as-scientists-crack-the-human-genome-11363988716324">human genome sequence</a> had been completed, he hailed the breakthrough as “the most important, most wondrous map ever produced by humankind”. The scientific achievement was placed on par with the moon landings.</p>
<p>It was hoped that having access to the sequence would transform our understanding of human disease <a href="https://web.ornl.gov/sci/techresources/Human_Genome/project/clinton3.shtml">within 20 years</a>, leading to better treatment, detection and prevention. The famous <a href="https://science.sciencemag.org/content/291/5507/1304.full">journal article</a> that shared our genetic ingredients with the world, published in February 2001, was welcomed as a “Book of Life” that could revolutionise medicine by showing which of our genes led to which illnesses.</p>
<p>But in the two decades since, the sequence has underwhelmed. The potential of our newfound genetic self-knowledge has not been fulfilled. Instead, what has emerged is a new frontier in genetic research: new questions for a new batch of researchers to answer. </p>
<p>Today, the gaps between our genes, and the switches that direct genetic activity, are emerging as powerful determinants behind how we look and how we get ill – perhaps deciding <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877666/">up to 90%</a> of what makes us different from one another. Understanding this “<a href="https://theconversation.com/discovering-how-genetic-dark-matter-plays-a-role-in-mental-illness-is-just-the-tip-of-the-iceberg-for-human-health-142326">genetic dark matter</a>”, using the knowledge provided by the human genome sequence, will help us to push further into our species’ genetic secrets.</p>
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<figcaption><span class="caption">The announcement was first made in a joint press conference between President Bill Clinton and Prime Minister Tony Blair in 2000.</span></figcaption>
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<h2>Unravelled code</h2>
<p>Cracking the human genetic code took 13 years, US$2.7 billion (£1.9 billion) and hundreds of scientists peering through over 3 billion base pairs in our DNA. Once mapped, our genetic data helped projects like the <a href="https://depmap.sanger.ac.uk/">Cancer Dependency Map</a> and the <a href="https://www.genome.gov/about-genomics/fact-sheets/Genome-Wide-Association-Studies-Fact-Sheet">Genome Wide Association Studies</a> better understand the diseases that afflict humans.</p>
<p>But some results were disappointing. Back in 2000, as it was becoming clear the genome sequence was imminent, the genomics community began excitedly placing bets predicting how many genes the human genome would contain. Some bets were as high as 300,000, others as low as 40,000. For context, the onion genome contains 60,000 genes.</p>
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<a href="https://theconversation.com/explainer-what-is-a-gene-12951">Explainer: what is a gene?</a>
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<p>Dispiritingly, it turned out that our genome contains roughly the same number of genes as a mouse or a fruit fly (around 21,000), and three times less than <a href="https://www.sciencedirect.com/science/article/abs/pii/S2352407316300166">an onion</a>. Few would argue that humans are three times less complex than an onion. Instead, this discovery suggested that the number of genes in our genome had little to do with our complexity or our difference from other species, as had been previously assumed.</p>
<h2>Great responsibility</h2>
<p>Access to the human genome sequence also presented the scientific community with a huge number of important <a href="https://pubmed.ncbi.nlm.nih.gov/1825074/">ethical questions</a>,
underscored in 2000 by Prime Minister Tony Blair when he cautioned: “With the power of this discovery comes the responsibility to use it wisely.”</p>
<p>Ethicists were particularly concerned about questions of “genetic discrimination”, like whether our genes could be used against us as evidence in a court of law, or as a basis for exclusion: a new kind of twisted hierarchy determined by our biology.</p>
<p>Some of these concerns were addressed by legislation against <a href="https://www.genome.gov/about-genomics/policy-issues/Genetic-Discrimination">genetic discrimination</a>, like the US Genetic Information Nondiscrimination Act of 2008. Other concerns, like those around so-called “designer babies”, are still being put to the test today.</p>
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<strong>
Read more:
<a href="https://theconversation.com/should-we-edit-the-genomes-of-human-embryos-a-geneticist-and-social-scientist-discuss-100355">Should we edit the genomes of human embryos? A geneticist and social scientist discuss</a>
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<p>In 2018, human embryos were gene edited by a Chinese scientist, using a method called CRISPR which allows targeted sections of DNA to be snipped off and replaced with others. The scientist involved was subsequently <a href="https://www.nature.com/articles/d41586-020-00001-y">jailed</a>, suggesting that there remains little appetite for <a href="https://www.who.int/ethics/topics/human-genome-editing/WHO-Commissioned-Ethics-paper-March19.pdf">human genetic experimentation</a>. </p>
<p>On the other hand, to <a href="https://www.nature.com/articles/d41586-019-01906-z">deny available genetic treatments</a> to willing patients may one day be considered unethical – just as some countries have chosen to legalise euthanasia on ethical grounds. Questions remain about how humanity should handle its genetic data.</p>
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<figcaption><span class="caption">The Chinese scientist He Jiankui announced in 2018 that he had created gene-edited twins. He was jailed in 2019.</span></figcaption>
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<h2>Disease diversions</h2>
<p>With human gene editing still highly contentious, researchers have instead looked to find out which genes may be responsible for humanity’s illnesses. Yet when scientists <a href="https://www.genome.gov/about-genomics/fact-sheets/Genome-Wide-Association-Studies-Fact-Sheet">investigated which genes</a> are linked to human diseases, they were met with a surprise. After comparing huge samples of human DNA to find whether certain genes led to certain illnesses, they found that many unexpected sections of the genome were involved in the development of human disease.</p>
<p>The genome contains two sections: the coding genome, and the non-coding genome. The coding genome represents just 1.7% of our DNA, but is responsible for coding the proteins that are the essential building blocks of life. Genes are defined by their ability to code proteins: so 1.7% of our genome consists of genes. </p>
<p>The non-coding genome, which makes up the remaining 98.3% of our DNA, doesn’t code proteins. This largely unknown section of the genome was once dismissed as “junk DNA”, previously thought to be useless. It contained no protein-creating genes, so it was assumed the non-coding genome had little to do with the stuff of life.</p>
<p>Bewilderingly, scientists found that the <a href="https://science.sciencemag.org/content/306/5696/636.abstract">non-coding genome</a> was actually responsible for the majority of information that <a href="https://pubmed.ncbi.nlm.nih.gov/28622505/">impacted disease development</a> in humans. Such findings have made it clear that the non-coding genome is actually far more important than previously thought.</p>
<h2>Enhanced capabilities</h2>
<p>Within this non-coding part of the genome, researchers have subsequently found short regions of DNA called enhancers: gene switches that turn genes on and off in different tissues at different times. They found that enhancers needed to shape the embryo have changed very <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561167/">little during evolution</a>, suggesting that they represent a major and important source of genetic information.</p>
<p>These studies inspired one of us, Alasdair, to explore the possible role of enhancers in behaviours such as alcohol intake, anxiety and fat intake. By comparing the genomes of mice, birds and humans we identified an enhancer that has changed relatively little over 350 million years – suggesting its importance in species’ survival. </p>
<p>When we used CRISPR genome editing to delete this enhancer from the mouse genome, those mice <a href="https://pubmed.ncbi.nlm.nih.gov/31445429/">ate less fat</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/32203157/">drank less alcohol</a>, and displayed reduced anxiety. While these may all sound like positive changes, it’s likely that these enhancers evolved in calorifically poor environments full of predators and threats. At the time, eating high-calorie food sources such as fat and fermented fruit, and being hyper-vigilant of predators, would have been key for survival. However, in modern society these same behaviours may now contribute to obesity, alcohol abuse and chronic anxiety.</p>
<p>Intriguingly, subsequent genetic analysis of a <a href="https://www.ukbiobank.ac.uk/">major human population cohort</a> has shown that changes in the same human enhancer were also associated with <a href="https://pubmed.ncbi.nlm.nih.gov/32203157/">differences in alcohol intake and mood</a>. These studies demonstrate that enhancers are not only important for normal physiology and health, but that changing them could result in changes in behaviour that have major implications for human health.</p>
<p>Given these new avenues of research, we appear to be at a crossroads in genetic biology. The importance of gene enhancers in health and disease sits uncomfortably with our relative inability to identify and understand them. </p>
<p>And so in order to make the most of the sequencing of the human genome two decades ago, it’s clear that research must now look beyond the 1.7% of the genome that encodes proteins. In exploring uncharted genetic territory, like that represented by enhancers, biology may well locate the next swathe of healthcare breakthroughs.</p>
<p><em>This article was updated on February 21, 2021 to clarify that DNA base pairs are not made from proteins.</em></p><img src="https://counter.theconversation.com/content/155349/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Alasdair Mackenzie receives funding from the BBSRC, Tenovus (Scotland) and Medical Research Scotland</span></em></p><p class="fine-print"><em><span>Andreas Kolb 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 achievement didn’t live up to the hype, but it has illuminated new areas of ‘genetic dark matter’.Alasdair Mackenzie, Reader, Molecular Genetics, University of AberdeenAndreas Kolb, Senior Research Fellow, The Rowett Institute, University of AberdeenLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1463982020-09-17T19:50:14Z2020-09-17T19:50:14ZWhy we need a global citizens’ assembly on gene editing<figure><img src="https://images.theconversation.com/files/358550/original/file-20200917-24-1wko0xl.jpg?ixlib=rb-1.1.0&rect=206%2C188%2C5784%2C3799&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Developments in <a href="https://theconversation.com/au/topics/gene-editing-18986">gene editing</a> are often met with moral panic. Every new announcement raises outrage over the audacity of scientists “playing God”. The existence of <a href="https://theconversation.com/mutant-malaria-parasites-resistant-to-antimalarial-atovaquone-cannot-spread-new-research-57359">mutant mosquitoes</a> and <a href="https://edition.cnn.com/2019/08/16/opinions/gene-edit-dangers-opinion-klitzman/index.html">designer babies</a> are often framed as threats – evidence that science fiction has crossed over into real life.</p>
<p>There are clear dangers when the language of fear and scandal hijack public conversations on complex matters. But this doesn’t mean we should leave the discussion on genome editing – the process of altering an organism’s genetic sequence to produce favourable characteristics or remove unwanted ones – solely to scientists.</p>
<p>That danger was sharply underscored in 2018, when a young Chinese researcher announced he had engineered the birth of what may very well be the <a href="https://theconversation.com/designer-babies-wont-be-common-anytime-soon-despite-recent-crispr-twins-108342">first genetically modified humans</a>. “I feel proud,” he told the public, a year before he was <a href="https://www.sciencemag.org/news/2019/12/chinese-scientist-who-produced-genetically-altered-babies-sentenced-3-years-jail">jailed for forgery</a>.</p>
<p>And so we reach an impasse. As global leaders face pressure to regulate genome editing, questions about who drives these ethical debates persist. Should leaders listen to scientists, who may be vulnerable to moral blindness, or to the public, some of whom may be convinced their last Whopper contained a Frankenfood patty because an Instagram influencer told them so?</p>
<h2>The impasse doesn’t have to be permanent</h2>
<p>In recent years, ordinary citizens have become more empowered to collectively learn, deliberate, reflect, and put forward recommendations on divisive and technical policy issues. The <a href="https://www.oecd.org/gov/innovative-citizen-participation-and-new-democratic-institutions-339306da-en.htm">OECD</a> calls this the “<a href="https://carnegieeurope.eu/2019/11/26/new-wave-of-deliberative-democracy-pub-80422">deliberative wave</a>”. Processes like citizen juries or online town halls have been used to provide public input not only on topical issues such as <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/j.1369-7625.2010.00637.x">e-health</a> or <a href="https://www.tandfonline.com/doi/abs/10.1080/13549839708725520?journalCode=cloe20">waste management</a>, but also on issues that affect future generations, like <a href="https://connect2parliament.com/resources/">mitochondiral donation</a>.</p>
<p><a href="https://citizensassemblies.org/">Citizens’ assemblies</a> are forums in which a randomly selected, demographically diverse group of laypeople come together, typically for several days at a time, to deliberate over a policy issue. This allows them to learn more about the issue, scrutinise expert information, engage the arguments of advocates representing different sides, and deliberate with their fellow participants about possible ways forward.</p>
<p>These assemblies can be viewed as a counterbalance to the growing prevalence of public conversations shaped by disinformation, clickbait culture, hyper-partisanship, and distrust of experts.</p>
<p>A citizens’ assembly is a fitting approach to clarify controversies on genome editing, particularly around its ethics.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/358551/original/file-20200917-20-1r0pmxw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Embryo modification illustration" src="https://images.theconversation.com/files/358551/original/file-20200917-20-1r0pmxw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/358551/original/file-20200917-20-1r0pmxw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=348&fit=crop&dpr=1 600w, https://images.theconversation.com/files/358551/original/file-20200917-20-1r0pmxw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=348&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/358551/original/file-20200917-20-1r0pmxw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=348&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/358551/original/file-20200917-20-1r0pmxw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=437&fit=crop&dpr=1 754w, https://images.theconversation.com/files/358551/original/file-20200917-20-1r0pmxw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=437&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/358551/original/file-20200917-20-1r0pmxw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=437&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">A citizens’ assembly on gene editing would allow for democratic deliberation on the risks involved.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
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<h2>A groundbreaking global experiment</h2>
<p>We are among 25 experts on deliberative democracy and genome editing who have <a href="https://science.sciencemag.org/cgi/doi/10.1126/science.abb5931">published an article today in the journal Science</a>, making a case for a <a href="https://www.globalca.org/">Global Citizens’ Assembly on Genome Editing</a> </p>
<p>We envisage a process that would convene at least 100 people from all over the world, none of whom can claim expertise or a history of advocacy on this issue. After learning about the issue from a national perspective, they would gather for five days to deliberate over whether there should be a set of global principles for the regulation of genome editing technologies. The challenge of getting a representative sample of the world is not lost on us, although we are committed to ensuring a broad spread of participants representing different nationalities, ages, religions, levels of education, genders and cultures. </p>
<p>This would be a groundbreaking global experiment. It would be the first example of a global citizens’ assembly, and it remains to be seen whether national governments and institutions such as the World Health Organisation and the Food and Agriculture Organisation would seriously consider its recommendations.</p>
<p>But there are good reasons to think our global citizens’ assembly would be a meaningful undertaking.</p>
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<a href="https://images.theconversation.com/files/358552/original/file-20200917-18-u5zhop.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Illustration of a round table" src="https://images.theconversation.com/files/358552/original/file-20200917-18-u5zhop.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/358552/original/file-20200917-18-u5zhop.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=574&fit=crop&dpr=1 600w, https://images.theconversation.com/files/358552/original/file-20200917-18-u5zhop.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=574&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/358552/original/file-20200917-18-u5zhop.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=574&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/358552/original/file-20200917-18-u5zhop.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=721&fit=crop&dpr=1 754w, https://images.theconversation.com/files/358552/original/file-20200917-18-u5zhop.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=721&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/358552/original/file-20200917-18-u5zhop.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=721&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">An effective citizens’ assembly would have participants from varying backgrounds and demographics, to be as inclusive as possible.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
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<h2>Evolving evidence</h2>
<p>A decade ago, the idea of citizens’ assemblies may have been dismissed by sceptics as pie in the sky. Here in Australia, the idea of a citizens’ assembly may have been tarnished by its identification with a partisan agenda, such as when former prime minister <a href="https://www.tandfonline.com/doi/full/10.1080/10361146.2013.786675?casa_token=nEsR3ITZtQ4AAAAA%3A3AQpuwuK34KX-XgyaQeItF4cLzAkaze3QS4v-S1yXq1B9w2BmN9ocI9L9KgmG2fCdrX9a8kRtyQjq1w">Julia Gillard</a> called for a citizens’ assembly on climate change. But today, citizens’ assemblies have begun to establish a credible track record.</p>
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Read more:
<a href="https://theconversation.com/a-novel-idea-on-climate-change-ask-the-people-1962">A novel idea on climate change: ask the people</a>
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<p>Last year, French President Emmanuel Macron invited 150 randomly selected citizens to consider ways to reduce the country’s carbon emissions by at least 40% within a decade. <a href="https://www.france24.com/en/20200622-french-citizens-council-on-the-environment-proposes-making-ecocide-illegal">Over nine months</a>, the assembly listened to more than 100 climate experts, with communications experts also on hand to help answer technical questions. </p>
<p>An assembly that included a 16-year-old student, a bus driver and a former fireman engaged in rigorous deliberation on the complex issues involved in ecological transition, even as a pandemic was unfolding. In the end, among other recommendations, the assembly endorsed making <a href="https://www.euronews.com/living/2020/06/25/france-wants-to-make-hurting-the-planet-illegal-but-what-is-ecocide">ecocide</a> a criminal act. Macron promised to put this recommendation to a national referendum.</p>
<p>There are many other examples of citizens’ assemblies that have contributed to enriching public conversations and policy-making. The Canadian province of British Columbia set up a <a href="https://participedia.net/case/1">Citizens’ Assembly on Electoral Reform</a> that successfully preceded a referendum. And the <a href="https://participedia.net/case/5316">Irish Citizens’ Assembly</a> on abortion and same-sex marriage informed a divisive debate about constitutional reform.</p>
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Read more:
<a href="https://theconversation.com/fearmongering-is-scary-not-genetic-technologies-themselves-92171">Fearmongering is scary, not genetic technologies themselves</a>
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<p>The stakes are high in the Global Citizens’ Assembly on Genome Editing. On the line are the legitimacy of policies and regulations based on the extent to which they reflect the values of ordinary citizens whose lives will potentially be affected by these technologies. </p>
<p>Beyond its impact on regulation, however, this democratic experiment can show the way on how citizens, scientists, and policymakers can talk about a fast-moving technology with more care, better information, and democratic deliberation.</p><img src="https://counter.theconversation.com/content/146398/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Nicole Curato receives funding from the Australian Research Council for project titled Global Citizen Deliberation: Analysing a Deliberative Documentary.</span></em></p><p class="fine-print"><em><span>Simon Niemeyer receives funding from the Australian Research Council for project titled Global Citizen Deliberation: Analysing a Deliberative Documentary.</span></em></p>Our approach to controversial technologies shouldn’t be guided by scientists alone, nor by peddlers of misinformation on social media. A citizens’ assembly could walk the line between the two.Nicole Curato, Associate Professor, Centre for Deliberative Democracy and Global Governance, University of CanberraSimon Niemeyer, Professor in Deliberative Democracy and Environmental Governance, University of CanberraLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1284342020-01-15T14:07:39Z2020-01-15T14:07:39ZHuman gene editing: who decides the rules?<figure><img src="https://images.theconversation.com/files/308787/original/file-20200107-123403-1br8ey5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Gene editing technology allows scientists to make changes to an organism’s DNA. It has made it possible to create <a href="https://milkgenomics.org/article/genetic-editing-eliminates-dairy-cattle-horns/">cattle without horns</a>, <a href="https://newfoodeconomy.org/international-space-station-gene-edited-tomato/">tomatoes</a> that ripen slowly over time, and even <a href="https://www.synthego.com/blog/gene-drive-malaria">mosquitoes</a> that are incapable of transmitting malaria. </p>
<p>The next frontier is human gene editing. Its potential is undeniable, and it provides the opportunity to edit disease out of the <a href="https://www.britannica.com/science/human-genome">human genome</a>. </p>
<p>Gene editing in humans takes one of two forms. In somatic gene editing, changes are made to DNA in a person’s body cells. In <a href="https://www.geneticsandsociety.org/internal-content/about-human-germline-gene-editing">germline editing</a>, changes are made to the DNA in embryos, sperm or egg cells. The <a href="https://news.harvard.edu/gazette/story/2019/01/perspectives-on-gene-editing/">difference</a> between them is that somatic gene editing affects that one person only, while germline editing results in changes in that person and their descendants.</p>
<p>Germline editing is more ethically controversial as it allows some control over what people of the future may be like. <a href="https://www.geneticsandsociety.org/topics/human-genetic-modification">More than 40 countries prohibit it</a> in their laws. In South Africa, however, the law does not mention human somatic or germline editing at all. </p>
<p>Scientists around the world recently called for a <a href="https://www.nature.com/articles/d41586-019-00726-5">five-year moratorium</a> on gene editing of humans until the technology can be proven to be safe and efficient. The call follows the <a href="https://www.bbc.com/news/health-48496652">gene editing of two children by the Chinese scientist</a> He Jiankui in 2018. Jiankui performed germline editing on the children as embryos to try to make them resistant to HIV acquisition. This was labelled as <a href="https://www.newyorker.com/news/daily-comment/he-jiankui-and-the-implications-of-experimenting-with-genetically-edited-babies">experimentation</a> because the safety of gene editing in humans hasn’t been proven. At the end of 2019 Jiankui was <a href="https://theconversation.com/prison-sentence-for-creator-of-first-crispr-babies-reignites-ethical-debate-129268">sentenced</a> to three years in prison. </p>
<p>The scientific community agreed that <a href="https://www.nature.com/articles/d41586-018-07545-0">Jiankui had crossed the line</a>, but is it really fair for them to make this decision? Gene editing has the potential to make an impact on the human race, so shouldn’t everyone have a voice in this conversation?</p>
<p>As an <a href="https://law.ukzn.ac.za/team/ms-sheetal-soni/">academic</a> who teaches international law and bioethics, I believe this is a debate that must take place at the global level. International bodies such as the <a href="https://www.who.int/ethics/topics/human-genome-editing/en/">World Health Organisation</a> and the <a href="http://arrige.org/">Association for Responsible Research and Innovation in Genome Editing</a> are trying to facilitate this. </p>
<p>Gene editing needs more than legal regulation. It should also be politically and ethically acceptable. And the public should have a say on the issues. </p>
<h2>Political legitimisation</h2>
<p>International law is based on the <a href="https://www.un.org/en/sections/issues-depth/international-law-and-justice/index.html">principle of consent</a>. States <em>choose</em> to be bound by the rules. Only certain international laws can be enforced in international courts and these courts don’t bind all states. States make – and avoid – treaties and agreements based on political ties. It is difficult to bind states to legal rules at the international level because there isn’t always consensus on the issues. </p>
<p>The <a href="https://www.coe.int/en/web/bioethics/oviedo-convention">Convention on Human Rights and Biomedicine</a> also known as the Oviedo Convention is the only international legally binding instrument on the protection of human rights in the biomedical field. It’s binding on 29, mostly European, countries. Its application outside Europe is therefore limited. But it is still important to consider its provisions as it represents agreement between some countries on these issues. </p>
<p>Article 13 states that “an intervention seeking to modify the human genome may only be undertaken for preventive, diagnostic, or therapeutic purposes and <em>only if its aim is not to introduce any modification in the genome of any descendants</em>”. This is interpreted as permitting somatic gene editing, but prohibiting germline editing. </p>
<p>Gene editing has created a new <a href="https://www.scientificamerican.com/article/race-to-the-moon/">“race to the moon”</a>, with countries trying to be the pioneers in new technology. It is difficult to oblige countries to restrict their technological capacity as this is often linked to their political power. </p>
<p>This is why many countries are not keen on regulating gene editing. They want to push ahead with developing the technology and be the first to bring it to human use. </p>
<h2>Ethical legitimisation</h2>
<p>The idea of applying gene editing to humans is fraught with <a href="https://nuffieldbioethics.org/assets/pdfs/genome-editing-evidence-Vlaams-Instituut-voor-Biotechnologie.pdf">ethical issues</a>. They include the creation of <a href="https://interestingengineering.com/designer-babies-gene-editing-and-the-controversial-use-of-crispr">“designer babies”</a>, treatment for genetic diseases being accessible only to the wealthy minority, and deciding when gene editing may be used and when it should be banned. These issues have been raised in relation to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570985/">other medical technologies</a>, and are being revived in relation to gene editing. But the <a href="https://futurism.com/crispr-genetic-engineering-change-world">potential benefits</a> are there and need to be debated. </p>
<h2>Public engagement</h2>
<p>Gene editing has the ability to affect people’s common genetic heritage, and it should not be scientists alone who determine what should or should not be allowed. The public <a href="https://www.americanscientist.org/article/the-gene-editing-conversation">needs information</a> about the risks and benefits, and inclusion in the debate over acceptable standards. </p>
<p>The only way to place regulation of gene editing on the political agenda is to get people talking about it. The issue of climate change provides a good example of this. It’s through social mobilisation by citizens that the <a href="https://www.vox.com/2019/9/17/20864740/greta-thunberg-youth-climate-strike-fridays-future">climate change movement has gathered momentum</a> and placed the issue on the agenda. </p>
<p>Gene editing provides an opportunity for the public to participate in developing a regulatory framework. To some extent, this public engagement is already happening, through the media and documentary series such as Netflix’s <a href="https://www.netflix.com/za/title/80208910"><em>Unnatural Selection</em></a>. But these platforms often suggest Western narratives which aren’t applicable in every context. This is especially relevant for countries where traditional medicine is a norm for many citizens and private healthcare is often out of reach. Countries may have language, cultural and traditional barriers which these narratives don’t cater for. There’s <a href="https://www.nature.com/articles/d41586-018-03269-3">no one-size-fits-all model for public engagement</a>. </p>
<p>This isn’t uncharted territory. Engagement with specific populations has already been done in Africa, most notably with the <a href="http://www.scielo.org.za/pdf/samj/v109n6/05.pdf">San population</a>. The first <a href="http://bio-economy.org.za/2019/12/19/attending-the-1st-south-african-conference-on-gene-editing/">South African Gene Editing Conference</a> was recently held at the University of Witwatersrand in Johannesburg. It was a crucial first step towards a conversation on gene editing on the African continent. </p>
<p>It’s important to consider the religious, social and cultural context when developing a regulatory framework. Gene editing gives people control over human genetics which was previously impossible. It presents the opportunity to remove disease from the human population. The time is ripe to embrace this technology so that it’s safe to use in humans and to establish a framework within which it may be applied.</p><img src="https://counter.theconversation.com/content/128434/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sheetal Soni is a an academic at the School of Law at the University of KwaZulu-Natal, where she lectures Bioethics, International Law and Intellectual Property Law. She is also a member of the Association for Responsible Research in Genome Editing (ARRIGE). She has received funding from the organisation to attend its annual general meeting. </span></em></p>The debate about gene editing will help shape the future of the human race. But how should the discussion get started?Sheetal Soni, Researcher, Lecturer, Attorney, University of KwaZulu-NatalLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1274062019-12-03T14:07:10Z2019-12-03T14:07:10ZHuman genetic enhancement might soon be possible – but where do we draw the line?<figure><img src="https://images.theconversation.com/files/304926/original/file-20191203-67028-1bdybdw.jpg?ixlib=rb-1.1.0&rect=35%2C8%2C5955%2C3979&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">How far will we allow genetic enhancement to go?</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/genetic-engineering-gene-manipulation-concept-hand-607718810?src=b9cbd285-db86-4e21-b8e7-278d24e57648-1-0">vchal/ Shutterstock</a></span></figcaption></figure><p>The <a href="https://www.youtube.com/watch?v=th0vnOmFltc&t=3s">first genetically edited children</a> were born in China in late 2018. Twins Lulu and Nana had a <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa1300662">particular gene</a> – known as CCR5 – modified during embryonic development. The aim was to make them (and their descendants) resistant to HIV. By some definitions, this would be an example of human enhancement. </p>
<p>Although there is <a href="https://www.sciencedirect.com/science/article/pii/S0002929717302471">still a long way to go</a> before the technology is safe, this example has shown it’s possible to edit genes that will continue being inherited by genetic offspring for generations. However, we don’t yet know what effect these genetic changes will have on the overall health of the twins throughout life. Potential unintended changes to other genes is a grave concern which is limiting our use of gene editing technology at the moment – but this limit won’t always be present.</p>
<p>As we increasingly become less limited by what is scientifically achievable in the realm of gene editing for enhancement, we rely more heavily on ethical – rather than practical – limits to our actions. In fact, the case of Lulu and Nana <a href="https://www.hup.harvard.edu/catalog.php?isbn=978067497671">might never have happened</a> if both scientific and ethical limits had been more firmly established and enforced. </p>
<p>But in order to decide these limits, the expert community needs one important contribution: public opinion. Without the voice of the people, regulations are unlikely to be followed. In a worst-case scenario, a lack of agreed-upon regulations could mean the emergence of dangerous black markets for genetic enhancements. These come with safety and equity issues. In the meantime, experts have called for a <a href="https://www.ncbi.nlm.nih.gov/pubmed/28796468">temporary international ban</a> on the use of gene editing technologies until a broad societal consensus has been established. </p>
<p>What should this broad consensus be? <a href="https://nuffieldbioethics.org/publications/genome-editing-and-human-reproduction">Current guidance in the UK</a> is theoretically in favour of gene editing for treatment purposes in the future – if certain requirements regarding safety and the intentions of editing are met. This includes eliminating unintentional changes to other genes as a result of genetic enhancements, and that edits serve the welfare of the individuals involved. But when it comes to enhancement, ethical limits are harder to determine as people have different views on what’s best for ourselves and society.</p>
<p>One thing to consider with a technology like gene editing is that it affects more people than just the individual whose genes have been edited – and in some cases, those with edited genes could be unfairly better off than those who haven’t had their genes enhanced.</p>
<p>For example, if it were possible to enhance genes to improve facial symmetry or make a person more confident, it might mean these people are <a href="https://www.hofstra.edu/pdf/orsp_shahani-denning_spring03.pdf">more likely to find employment</a> in a competitive market, compared to those who haven’t had their genes edited for these characteristics. Future generations will also inherit and carry these enhancements in their DNA. In these <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4402029/">ethical dilemmas</a>, in order for one person to win, many people must (often unwittingly) lose.</p>
<h2>For the many not the few</h2>
<p>Surprisingly, the field of economics might provide us with one useful way of thinking through the ethics of genetic enhancement. In economics, an advantage that is only beneficial to one person because it makes them relatively better than everyone else is often called a <a href="https://www.hup.harvard.edu/catalog.php?isbn=9780674497900">“positional” good</a>. Positional goods rely on other people being worse off. This means they are less beneficial to the individual as other people become better off, as in the competitive employment example.</p>
<p>A <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4402029/">typical example</a> of a positional good related to enhancement is height. It has been shown that, particularly for men, being taller is associated with better outcomes in life – such as having a higher annual household income.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/304929/original/file-20191203-67002-1883f48.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/304929/original/file-20191203-67002-1883f48.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/304929/original/file-20191203-67002-1883f48.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/304929/original/file-20191203-67002-1883f48.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/304929/original/file-20191203-67002-1883f48.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/304929/original/file-20191203-67002-1883f48.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/304929/original/file-20191203-67002-1883f48.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">‘Positional goods’ only benefit the individual.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/profile-shot-businesspeople-standing-row-height-145411717?src=93de3733-2733-4e6f-a736-af077e22b784-1-16">sirtravelot/Shutterstock</a></span>
</figcaption>
</figure>
<p>But being taller isn’t good in and of itself. For example, tall people <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4402029/">need to eat more food, they take up more space</a> and may be <a href="https://www.ncbi.nlm.nih.gov/pubmed/28296269">more prone to osteoarthritis</a> and other health conditions later in life. If everyone was given access to height enhancements, any economic advantages a person might gain from being taller would either no longer exist, because everyone else would also be taller, or might be outweighed by these other height-based disadvantages.</p>
<p>However, this is not the case with all goods. Goods that can benefit both the individual and other people are said to have <a href="https://www.nature.com/articles/s41599-019-0265-2">“collective benefit”</a>. An example of this might be getting your flu shot or the MMR vaccine. If a person takes measures to protect themselves from catching an infectious disease (or, perhaps in the future, having their genes edited to make them immune to a certain infectious disease), that person also benefits the rest of society by not carrying and spreading the disease to others. If everyone gets the flu shot, or enhances their immune systems, society is benefited even more through the reduced disease burden. </p>
<p>Lifting the ban just on enhancements that provide collective benefit may be more morally defensible than also allowing those that only produce positional goods. Otherwise, if we allowed everyone to pursue enhancements that produce positional goods, there may be little benefit to enhancement either to the individual, or to everyone else, once the costs to the rest of society are taken into account, as with the height example. But there may be benefits to society more generally if we provide access to enhancements that create or support collective-benefiting goods such as immune system enhancements.</p>
<p>Both experts and society still need to decide what constitutes ethical use of gene editing for enhancement, and what benefits enhancements might have to either the individual or society – or both. This is perhaps one way of deciding whether and how human genetic enhancement should be allowed in the future.</p><img src="https://counter.theconversation.com/content/127406/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Tess Johnson 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>Ideas from economics might help us decide the most ethical way of using gene editing technology for human enhancement in the future.Tess Johnson, Doctor of Philosophy candidate, University of OxfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1219122019-08-15T11:14:47Z2019-08-15T11:14:47ZWhat’s the right way for scientists to edit human genes? 5 essential reads<figure><img src="https://images.theconversation.com/files/288064/original/file-20190814-136222-xtmn4o.jpg?ixlib=rb-1.1.0&rect=431%2C449%2C5290%2C3520&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Ethical frameworks, rules, laws: all try to have their say.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/doctor-prepares-special-media-growing-embryos-1447342460?src=XFXBbEV0tU5iihvrK1Vv0A-1-12">Tati9/Shutterstock.com</a></span></figcaption></figure><p>Since scientists first figured out how to edit genes with precision using a technology called CRISPR, they’ve been grappling with when and how to do it ethically. Is it reasonable to edit human genes with CRISPR? What about human genes in reproductive cells that pass the edits on to future generations?</p>
<p>The <a href="http://nationalacademies.org/gene-editing/international-commission/index.htm?_ga=2.266036175.1969896713.1565792406-1004430421.1565792406">International Commission on the Clinical Use of Human Germline Genome Editing</a> convened on Aug. 13 to hash out guidelines about editing human embryos. The goal is to provide a framework that researchers around the globe can consult to ensure their work is in line with scientific consensus.</p>
<p>An earlier U.S. National Academies committee had already released recommendations in 2017. They called for caution – but were ambiguous enough for Chinese scientist He Jiankui to suggest he’d followed them even as he produced <a href="https://theconversation.com/how-a-scientist-says-he-made-a-gene-edited-baby-and-what-health-worries-may-ensue-107764">twin girls with CRISPR-edited genomes</a> late last year.</p>
<p>Here are five stories from our archive that explore how to ethically develop and regulate a potentially risky new technology.</p>
<h2>1. A voluntary pause</h2>
<p>No one denies the power of the CRISPR editing tool. It could allow doctors to one day cure genetic diseases, whether in adults who are living with medical conditions or in embryos that have not yet even been born. But there’s a lot of lab work yet to be done, as well as many conversations to be had, about the right way to proceed.</p>
<p>In 2015, a group of prominent scientists called for a voluntary freeze on germline editing – that is, changing sperm, eggs or embryos – until ethical issues could be resolved.</p>
<p>Chemical biologist <a href="https://theconversation.com/profiles/jeff-bessen-174263">Jeff Bessen</a> wrote that this approach has precedents in the scientific community, where many think it makes sense to take things slow and place “the right emphasis on <a href="https://theconversation.com/crispr-cas-gene-editing-technique-holds-great-promise-but-research-moratorium-makes-sense-pending-further-study-43371">safety and ethics without hampering research progress</a>.”</p>
<h2>2. Stringent hurdles before proceeding</h2>
<p>The National Academies’ 2017 report was meant to provide the scientific community with definitive guidance on the issue.</p>
<p><a href="https://theconversation.com/profiles/rosa-castro-303464">Rosa Castro</a>, a scholar of science and society, explained that the report gave the green light to modifying body cells and a yellow light to modifying reproductive cells that would allow the changes to be inherited by future progeny. The report’s goal was to ensure that “germline genome editing <a href="https://theconversation.com/safe-and-ethical-ways-to-edit-the-human-genome-73110">will be used only</a> to prevent a serious disease, where no reasonable alternatives exist, and under strong supervision.”</p>
<h2>3. Science marches on</h2>
<p>By later that year, a research group announced they’d successfully used CRISPR to modify human embryos, though the edited embryos weren’t implanted in women and were never born. Bioethics and public health professor <a href="https://scholar.google.com/citations?user=eXQqA5gAAAAJ&hl=en&oi=ao">Jessica Berg</a> wrote about the importance of <a href="https://theconversation.com/editing-human-embryos-with-crispr-is-moving-ahead-nows-the-time-to-work-out-the-ethics-81732">working out the ethical issues</a> of gene editing before researchers take the critical step of allowing modified embryos to develop and be born as babies.</p>
<blockquote>
<p>“Should there be limits on the types of things you can edit in an embryo? If so, what should they entail? These questions also involve deciding who gets to set the limits and control access to the technology.</p>
<p>"We may also be concerned about who gets to control the subsequent research using this technology. Should there be state or federal oversight? Keep in mind that we cannot control what happens in other countries.</p>
<p>"Moreover, there are important questions about cost and access.”</p>
</blockquote>
<h2>4. Babies born with edited genomes</h2>
<p>Most of the world reacted with shock in 2018 when a Chinese researcher announced he’d <a href="https://theconversation.com/how-a-scientist-says-he-made-a-gene-edited-baby-and-what-health-worries-may-ensue-107764">edited the germline cells of embryos</a> that went on to become twin baby girls. His stated goal was to protect them from HIV infection.</p>
<p>This development seemed to many researchers to be in violation of at least the spirit of the 2017 guidelines around human gene editing. Biomedical ethicist <a href="https://scholar.google.com/citations?user=yebS-LIAAAAJ&hl=en&oi=ao">G. Owen Schaefer</a> described the central objection: that the procedure was simply too risky, with the potential for unexpected and harmful health effects later in the girls’ lives outweighing any benefit.</p>
<p>He wrote that the “CRISPR babies” are “part of a disturbing pattern in reproduction: <a href="https://theconversation.com/rogue-science-strikes-again-the-case-of-the-first-gene-edited-babies-107684">rogue scientists bucking international norms</a> to engage in ethically and scientifically dubious reproductive research.”</p>
<h2>5. Rules and regs don’t guarantee ethical work</h2>
<p>Whatever the outcome of the current meeting, there may be a distinction between sticking to the rules and doing what’s right. Arizona State professor of life sciences <a href="https://theconversation.com/profiles/j-benjamin-hurlbut-608394">J. Benjamin Hurlbut</a> and applied ethicist <a href="https://scholar.google.com/citations?user=hOM4hNIAAAAJ&hl=en&oi=ao">Jason Scott Robert</a> underscored this point after Chinese scientist He Jiankui claimed he checked off the boxes laid out by the 2017 guidelines.</p>
<blockquote>
<p>“Public debate about the experiment should not make the mistake of <a href="https://theconversation.com/crispr-babies-raise-an-uncomfortable-reality-abiding-by-scientific-standards-doesnt-guarantee-ethical-research-108008">equating ethical oversight with ethical acceptability</a>. Research that follows the rules is not necessarily good by definition.”</p>
</blockquote>
<p>Guidelines and expectations can help define what the scientific community finds acceptable. But complying with the routines of oversight doesn’t guarantee a project is ethical. That’s a much more complicated question.</p>
<p><em>Editor’s note: This story is a roundup of articles from The Conversation’s archives.</em></p><img src="https://counter.theconversation.com/content/121912/count.gif" alt="The Conversation" width="1" height="1" />
CRISPR technology could have momentous effects if it’s used to edit genes that will be inherited by future generations. Researchers and ethicists continue to weigh appropriate guidelines.Maggie Villiger, Senior Science + Technology EditorLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1138272019-03-20T10:32:43Z2019-03-20T10:32:43ZA case against a moratorium on germline gene editing<figure><img src="https://images.theconversation.com/files/264849/original/file-20190320-93054-isf374.jpg?ixlib=rb-1.1.0&rect=132%2C0%2C5065%2C3509&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">What's the best way to put the brakes on current research?</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/embryologist-adding-sperm-egg-laboratory-reproductive-607661843">Okrasyuk/Shutterstock.com</a></span></figcaption></figure><p>Should researchers put the brakes on genetically engineering babies? Leading scientists and ethicists recently <a href="https://doi.org/10.1038/d41586-019-00726-5">called for a moratorium</a> on clinical applications of <a href="https://theconversation.com/editing-genes-shouldnt-be-too-scary-unless-they-are-the-ones-that-get-passed-to-future-generations-113627">germline gene editing</a>: inheritable alterations to the DNA of embryos to improve kids’ health or other features – or just “gene editing,” for short. </p>
<p>This declaration was prompted in part by the birth last year of the <a href="https://www.apnews.com/4997bb7aa36c45449b488e19ac83e86d">first gene-edited babies</a> in China. The birth was <a href="https://www.nature.com/articles/d41586-018-07545-0">roundly condemned</a> by experts and <a href="https://www.scmp.com/news/china/science/article/2182964/china-confirms-gene-edited-babies-blames-scientist-he-jiankui">may result</a> in charges against He Jiankui, the <a href="https://theconversation.com/us/topics/he-jiankui-63070">lead scientist involved</a>. </p>
<p>The call for a moratorium is grounded in two main concerns. Its supporters assert, first, that the risks of gene editing are simply too uncertain and potentially large to proceed. Secondly, the deeply controversial nature and potential social impact of altering human DNA means researchers need “<a href="http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=12032015a">broad societal consensus</a>” before proceeding.</p>
<p>The authors suggest a five-year pause to wait for more scientific progress and public dialogue. At that point, the authors propose, societies may choose to begin a path forward for gene editing, if risks are deemed acceptable and the process is fully transparent.</p>
<p>However, several scientists have <a href="https://www.statnews.com/2019/03/13/crispr-babies-germline-editing-moratorium/">pushed back</a> against the call for a moratorium, including gene-editing pioneer Jennifer Doudna and geneticist George Church. <a href="https://scholar.google.com/citations?user=yebS-LIAAAAJ&hl=en&oi=ao">As a biomedical ethicist</a>, I believe the objectors raise valid concerns about the relevance and usefulness of a moratorium that are worth reflecting upon.</p>
<h2>Plenty everyone agrees on</h2>
<p>To be sure, those for and against a moratorium actually agree on some key points.</p>
<p>Almost no one thinks the world is ready for clinical trials today, as more basic science is needed to minimize <a href="https://cosmosmagazine.com/biology/study-raises-fears-of-collateral-damage-in-gene-editing">risks like</a> editing the wrong bits of DNA, or “mosaicism,” where some but not all DNA in an embryo is altered. He Jiankui’s rogue science was <a href="https://theconversation.com/rogue-science-strikes-again-the-case-of-the-first-gene-edited-babies-107684">clearly unethical</a> for this and other reasons, including a lack of transparency and flaws in informed consent.</p>
<p>There is also no pushback against the idea that the world needs to have a <a href="https://doi.org/10.1038/d41586-018-03270-w">public conversation</a> about gene editing. Do you want to live in a society where embryos’ DNA is edited in order to improve the lives of the next generation? Are the risks of gene editing worth the benefits? Can and should we draw a bright line between editing for disease prevention and editing for enhancement? These questions cannot be answered only by experts, and require substantial public engagement.</p>
<p>Nevertheless, a divide over other issues remains.</p>
<p><iframe id="hAGmJ" class="tc-infographic-datawrapper" src="https://datawrapper.dwcdn.net/hAGmJ/1/" height="400px" width="100%" style="border: none" frameborder="0"></iframe></p>
<h2>Moratorium redundant where laws already exist</h2>
<p>Already, <a href="https://doi.org/10.1186/1477-7827-12-108">over 30 countries</a> prohibit this sort of gene editing, either by <a href="https://doi.org/10.1126/science.aad6778">law, regulation or enforceable guidelines</a>. For this reason, it was quite easy for the director of the U.S. National Institutes of Health to <a href="https://www.nih.gov/about-nih/who-we-are/nih-director/statements/nih-supports-international-moratorium-clinical-application-germline-editing">endorse the proposed moratorium</a> – the NIH, the <a href="https://www.nih.gov/about-nih/what-we-do/impact-nih-research/our-society">largest public funder of biomedical research in the world</a>, is already prohibited by law from funding clinical applications of gene editing. So a moratorium is at best redundant in those nations, perpetuating the status quo. </p>
<p>It is also liable to cause confusion. If a country or scientific body announces a moratorium as recommended, this could misleadingly imply that germline editing was previously permitted and unregulated. It could also suggest that some countries’ bans will expire in five years, when currently none has a time-limited prohibition.</p>
<h2>Arbitrariness of a blunt instrument</h2>
<p>At the same time, I believe a moratorium could work in countries that currently lack prohibitions on gene editing. It could help prevent rogue scientists from seeking environments that are relatively unregulated to pursue dubious experiments. <a href="https://www.technologyreview.com/s/602499/a-three-parent-child-was-conceived-in-mexico-because-the-us-wont-allow-it/">This is what happened</a> with the first births using mitochondrial replacement (so-called “3-parent IVF”): An American fertility doctor carried out part of the procedure in Mexico because he perceived the rules as laxer there.</p>
<p>Additionally, the call can be heard as an argument for reform of current laws and regulations: Society should revisit prohibitions and – depending on the evidence and popular opinion – consider rescinding them in five years’ time.</p>
<p>But <a href="https://edition.cnn.com/2019/03/13/health/inherited-dna-editing-moratorium-study/index.html">some researchers remain concerned</a> that a moratorium is an overly crude and arbitrary means of regulating a controversial new technology. While the technology is currently not fit for clinical use, are scientists so certain that it still won’t be within five years’ time? More flexible regulatory frameworks that do not include arbitrary timelines could better adapt to rapid scientific developments and shifts in public perceptions.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/264851/original/file-20190320-93051-7po435.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/264851/original/file-20190320-93051-7po435.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/264851/original/file-20190320-93051-7po435.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/264851/original/file-20190320-93051-7po435.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/264851/original/file-20190320-93051-7po435.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/264851/original/file-20190320-93051-7po435.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/264851/original/file-20190320-93051-7po435.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/264851/original/file-20190320-93051-7po435.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">In deciding how society should proceed on this front, members of the public have just as much say as experts.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/closeup-on-discussion-people-communicating-while-439213456">g-stockstudio/Shutterstock.com</a></span>
</figcaption>
</figure>
<h2>A call for public input – without public input</h2>
<p>Finally, it’s unclear whether a moratorium is consistent with the democratic norms that the proponents of a moratorium espouse. In particular, they reiterate the idea that researchers should only proceed with germline gene editing <a href="https://issues.org/on-human-gene-editing-international-summit-statement-by-the-organizing-committee/">if there is broad societal consensus</a> on how to proceed.</p>
<p>But shouldn’t a moratorium itself be subject to the requirement of broad societal consensus? Blanket prohibitions will have a substantial impact not just on the scientific community but on access for the rest of society to the potential fruits of research – a potential infringement of the <a href="https://unesdoc.unesco.org/ark:/48223/pf0000185558">human right to benefit from science</a>. Whether that infringement is justified is an important question that cannot be answered by experts alone.</p>
<p>To some extent, democratic countries that ban gene editing will have already undergone typical (if flawed) democratic processes to come to that decision. But in places that the moratorium is not redundant, it is reasonable to demand broad societal consensus before proceeding with a moratorium that even leading scientists don’t all agree on.</p>
<p>The cautious may argue that a presumption against gene editing is warranted before consensus can be established, because of the <a href="https://www.thehastingscenter.org/a-moratorium-on-gene-editing/">substantial individual risks</a> and <a href="https://www.nature.com/articles/s41431-017-0024-z">societal impact</a> of proceeding to alter the human genome for future generations. However, those societal risks are very substantial only if gene editing quickly becomes widespread. That is something careful regulation rather than a blanket prohibition might be well-suited to address. </p>
<p>In addition, I see it as somewhat problematic for experts to impose their own personal assessment of whether the risks outweigh the benefits of gene editing on the rest of society. Weighing risks and benefits is a fundamentally ethical issue, not one where scientific expertise can resolve the matter.</p>
<p>In the end, though, there seems to be broad agreement on the need for greater public deliberation over the questions related to germline gene editing: on whether gene editing is permissible, on whether a moratorium is appropriate – and more fundamentally, on what sort of a society we all want to live in.</p><img src="https://counter.theconversation.com/content/113827/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>Scientists and ethicists have called for a five-year moratorium on editing human genes that will pass on to future generations. Yes, society needs to figure out how to proceed – but is this the best way?G. Owen Schaefer, Research Assistant Professor in Biomedical Ethics, National University of SingaporeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1086582018-12-17T11:38:30Z2018-12-17T11:38:30ZChina’s win-at-all-costs approach suggests it will follow its own dangerous path in biomedicine<figure><img src="https://images.theconversation.com/files/250793/original/file-20181216-185252-pog7ka.jpg?ixlib=rb-1.1.0&rect=400%2C30%2C4546%2C2589&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Megacity Shenzhen, as seen from Hong Kong, is a center for Chinese finance and tech.</span> <span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/China-Shenzhen-Rising/b6f947b7e94d4cf6ba3d70b8d2512584/6/0">AP Photo/Kin Cheung</a></span></figcaption></figure><p><a href="https://theconversation.com/rogue-science-strikes-again-the-case-of-the-first-gene-edited-babies-107684">The world was shocked</a> by <a href="https://www.apnews.com/4997bb7aa36c45449b488e19ac83e86d">Chinese scientist He Jiankui’s recent claim</a> that he’d brought to term twin babies whose genes – inheritable by their own potential descendants – he had modified as embryos. The genetic edit, He said, was meant to make the girls resistant to HIV infection.</p>
<p>Scientists within China and across the world responded to the announcement <a href="https://www.nytimes.com/2018/11/26/health/gene-editing-babies-china.html">with a mixture of</a> <a href="https://www.nytimes.com/2018/11/30/world/asia/gene-editing-babies-china.html">incredulity and alarm</a>.</p>
<p>But as a <a href="http://hallamstevens.org">historian of biology</a> who has closely followed biomedicine in China over the past few years, I was less surprised by these developments. Set within the context of China’s <a href="https://doi.org/10.1038/d41586-018-07692-4">approach to biomedical ethics</a> and its rampant global ambitions, He’s actions fit into a wider pattern of dangerous excess.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/250794/original/file-20181216-185264-c6oan.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/250794/original/file-20181216-185264-c6oan.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/250794/original/file-20181216-185264-c6oan.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/250794/original/file-20181216-185264-c6oan.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/250794/original/file-20181216-185264-c6oan.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/250794/original/file-20181216-185264-c6oan.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/250794/original/file-20181216-185264-c6oan.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/250794/original/file-20181216-185264-c6oan.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">He Jiankui’s announcement included plenty of careful image cultivation.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/China-Gene-Edited-Babies/5673e068deba45ce82d5b3b5ae085bd6/4/0">AP Photo/Mark Schiefelbein</a></span>
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</figure>
<p>Since He did not publish any of his results in scientific journals there’s no way of knowing yet whether his claims are true, <a href="https://www.wsj.com/articles/gene-edited-babies-experiment-raises-concerns-11544616000">false</a> or exaggerated in some way. But what seems the most surprising outside of China is that He believed – gambled, perhaps – that his announcement would be met with congratulations and acclaim. Didn’t he know that he’d be condemned? Why take such a risk?</p>
<h2>Different history frames what’s acceptable</h2>
<p>China’s relationship to biomedical ethics is <a href="https://link.springer.com/article/10.1057%2Fbiosoc.2015.34">very different from that of the West</a>.</p>
<p>In the West, after-the-fact condemnation of Nazi medical experiments, the <a href="https://en.wikipedia.org/wiki/Tuskegee_syphilis_experiment">Tuskegee syphilis experiment</a> and other patient abuses led to the rise of <a href="http://rc.rcjournal.com/content/53/10/1330">Institutional Review Boards</a> that carefully regulate medical experimentation on humans. China has its own history of dubious medical research, including by <a href="https://en.wikipedia.org/wiki/Unit_731">Japanese scientists during World War II</a>, but it didn’t result in the development of similar kinds of home-grown bioethics institutions. Although many hospitals and universities in China do now have Institutional Review Boards, they’re <a href="http://www.wpro.who.int/health_research/ethics/challenges_and_issues_of_concerned_regarding_the_research_ethics_qinglihu.pdf">not nearly as established</a> – or consistent in their practices – as those in the U.S. and Europe. </p>
<p>This does not excuse He’s actions. After all, he was trained in the U.S. and was surely aware of Western norms. But He’s willingness to engage in undoubtedly risky and dangerous actions suggests that he was working in a very different ethical context. </p>
<p>Apart from merely an <a href="https://theconversation.com/crispr-babies-raise-an-uncomfortable-reality-abiding-by-scientific-standards-doesnt-guarantee-ethical-research-108008">absence of compelling ethical oversight</a>, the broader attitudes toward biomedical research in China are important in explaining He’s annoucement. In the West, the potential benefits of biomedicine and biotechnologies are often <a href="https://www.fda.gov/Safety/Biotechnology/ucm624416.htm">weighed against potential harms</a>. In Europe and the U.S., many people <a href="https://theconversation.com/mandatory-labels-with-simple-disclosures-reduced-fears-of-ge-foods-in-vermont-98915">view genetically modified foods</a> with caution and treat <a href="https://theconversation.com/20-years-after-dolly-everything-you-always-wanted-to-know-about-the-cloned-sheep-and-what-came-next-72655">cloning</a> and <a href="https://stemcells.nih.gov/info/basics/1.htm">stem cells</a> with outright distrust. </p>
<p>China came to biotech late in the game, <a href="https://doi.org/10.1007/s13238-017-0474-7">scraping into the Human Genome Project</a> in the 1990s. Even so, both the Chinese state and Chinese scientists saw the field as an area in which <a href="https://rowman.com/ISBN/9780742553064/Biology-and-Revolution-in-Twentieth-Century-China">China had a good chance of catching up to the West</a>. As such, it gambled heavily and has <a href="https://doi.org/10.1038/d41586-018-00542-3">invested much in biotech</a> and biomedicine. <a href="https://doi.org/10.1086/699235">Having followed</a> <a href="https://www.bgi.com/us/">one of China’s most prominent biotech companies</a> for years, I can attest that these fields are seen as critical to sustaining China’s growing population: feeding people through agricultural technologies and keeping people healthy through new medicines and therapies.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/250795/original/file-20181216-185240-1kaq6tl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/250795/original/file-20181216-185240-1kaq6tl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/250795/original/file-20181216-185240-1kaq6tl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/250795/original/file-20181216-185240-1kaq6tl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/250795/original/file-20181216-185240-1kaq6tl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/250795/original/file-20181216-185240-1kaq6tl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/250795/original/file-20181216-185240-1kaq6tl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/250795/original/file-20181216-185240-1kaq6tl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">In January 2018, Chinese scientists claimed they’d made the first primate clones.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Cloned-Monkeys/b928cdea7abb4be99475b70d852c05dd/2/0">Qiang Sun and Mu-ming Poo/Chinese Academy of Sciences via AP</a></span>
</figcaption>
</figure>
<p>The upshot of all this is that Chinese view biomedicine in dramatically positive terms. Advances in biomedicine can have an <a href="http://www.globaltimes.cn/content/1126725.shtml">almost heroic status within China</a>. </p>
<p>He’s claims about genetic modification fit this model. He has represented his use of genetic modification as a bold intervention to save the lives of twin girls and eliminate discrimination against HIV patients. He himself is (or at least was) somewhat of a heroic figure. He completed his Ph.D. at Rice University and postdoctoral training at Stanford before being sponsored by the Chinese government to return to his homeland under the “<a href="http://www.1000plan.org/en/">Thousand Talents Plan</a>,” which aims to recruit top scientists back to Chinese universities. In 2018, he was <a href="https://www.thehastingscenter.org/jiankuis-genetic-misadventure-china/">nominated for the China Youth Science and Technology Award</a>. He was a rising star.</p>
<h2>Moving fast and breaking things</h2>
<p>In 2012, back from the U.S., He Jiankui joined <a href="http://sustc.edu.cn/en/">Southern University of Science and Technology</a>, an institution set up in Shenzhen in 2011. This local setting is important too. Shenzhen, the city that sprang up from China’s first <a href="https://en.wikipedia.org/wiki/Special_economic_zones_of_China">Special Economic Zone</a>, was an experiment in China’s reform and opening. Since 1980, Shenzhen has been a <a href="https://www.press.uchicago.edu/ucp/books/book/chicago/L/bo24731869.html">zone of experimentation</a>, a place of high risk and high reward. Both penniless farmers and entrepreneurs have gone there to <a href="https://www.penguinrandomhouse.com/books/26101/factory-girls-by-leslie-t-chang/9780385520188/">make their fortune</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/250796/original/file-20181216-185258-1283jvn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/250796/original/file-20181216-185258-1283jvn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/250796/original/file-20181216-185258-1283jvn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/250796/original/file-20181216-185258-1283jvn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/250796/original/file-20181216-185258-1283jvn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/250796/original/file-20181216-185258-1283jvn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/250796/original/file-20181216-185258-1283jvn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/250796/original/file-20181216-185258-1283jvn.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">Shenzhen’s busy Seg electronics market is a popular place for hardware startup entrepreneurs to buy components for their inventions and prototypes.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/China-Shenzhen-Rising/48a79758747244a486996552bbcf46e1/5/0">AP Photo/Kelvin Chan</a></span>
</figcaption>
</figure>
<p>This has resulted in some great successes: Shenzhen is the home of Huawei, Tencent, BGI, BYD, and hundreds of other <a href="https://www.scmp.com/lifestyle/technology/enterprises/article/1765430/top-5-tech-giants-who-shape-shenzhen-chinas-silicon">thriving companies</a>. But such experiments have also generated problems. The capitalist excesses that have come with reform and opening up – <a href="https://www.forbes.com/sites/yanzhonghuang/2014/07/16/the-2008-milk-scandal-revisited/#4d669b0b4105">doctored milk</a>, <a href="https://www.cnn.com/2018/07/23/asia/faulty-vaccine-china-intl/index.html">fake vaccines</a> and <a href="https://en.wikipedia.org/wiki/Gutter_oil">gutter oil</a> – are now well known. And Shenzhen is a place where such excesses – particularly <a href="https://www.washingtonpost.com/news/wonk/wp/2017/08/14/trump-administration-goes-after-china-over-intellectual-property-advanced-technology/">violations of intellectual property rules</a> – have been particularly rampant.</p>
<p>He’s reckless experimentation looks like the result of such an attitude, as applied to biomedicine. It is not just scientific competition and a “<a href="https://www.nytimes.com/2018/11/30/world/asia/gene-editing-babies-china.html">drive to succeed</a>,” but arguably a wider atmosphere of success through excess. The release of a <a href="https://www.youtube.com/watch?v=th0vnOmFltc">YouTube video</a> alongside He’s announcement suggests that his actions are motivated by personal aggrandizement and <a href="https://theconversation.com/youtube-persuasion-and-genetically-engineered-children-107938">fame- and fortune-seeking</a>.</p>
<p>Like those other scandals involving tainted products, He’s genetic modification is yet another failure by the Chinese government to protect its vulnerable citizens – in this case, unborn children – from predatory individuals and companies. </p>
<p>From an even broader perspective, such excesses might be seen as collateral damage from global competition and rapid development. In developing “<a href="https://en.wikipedia.org/wiki/Socialism_with_Chinese_characteristics">socialism with Chinese characteristics</a>” and in its reform and opening up, China has followed its own political path, often proving <a href="https://foreignpolicy.com/2018/08/08/china-doesnt-want-to-play-by-the-worlds-rules/">unwilling to follow international norms</a>. And Shenzhen – the world’s capital of tech hardware development – has found its <a href="https://www.wired.com/beyond-the-beyond/2018/08/new-shanzhai-%E5%B1%B1%E5%AF%A8-shanzhai/">own models of innovation</a> that now rival Silicon Valley’s. Catching up with – and surpassing – the West has motivated divergent, and sometimes ugly, actions. Take the <a href="https://www.forbes.com/sites/davidvolodzko/2018/12/11/what-the-huawei-scandal-says-about-american/#56029c6751b0">recent scandal involving Huawei</a>, for instance. </p>
<p>China may decide to forge its own path in science, too, following trajectories that would not be possible in the West. For now, He <a href="https://qz.com/1474530/chinese-scientists-condemn-crispr-baby-experiment-as-crazy/">remains shunned within China</a>. But if his reckless experiments do turn out to be a world first, Chinese scientists may embrace them – and him.</p>
<p>Science and public policy scholar <a href="https://scholar.google.com/citations?user=OBu0OHEAAAAJ&hl=en&oi=ao">Caroline Wagner</a> has argued that He’s actions will <a href="https://news.osu.edu/crispr-babies-and-other-ethical-missteps-in-science-threaten-chinas-global-standing/">threaten China’s position in the global scientific order</a> by undermining the willingness of scientists elsewhere to collaborate with them: “A global system that works by reputation will shun those who do not play by the rules.” But these rules are Western ones. And China may decide it can go its own way.</p><img src="https://counter.theconversation.com/content/108658/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Hallam Stevens receives funding from the Ministry of Education, Singapore. </span></em></p>CRISPR babies may be just the beginning. China has a different take than the West on ethics and how to get ahead in business and other endeavors.Hallam Stevens, Associate Professor of History, Nanyang Technological UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1080092018-12-04T11:31:07Z2018-12-04T11:31:07ZCRISPR babies and other ethical missteps in science threaten China’s global standing<figure><img src="https://images.theconversation.com/files/248584/original/file-20181203-194944-g5btiu.jpg?ixlib=rb-1.1.0&rect=255%2C197%2C2443%2C1796&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">China's military may bear the brunt of hits to the country's scientific reputation.</span> <span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/China-Ivory-Coast/aa6bba3d6a184e99baeb42dc39b9e162/4/0">Roman Pilipey/Pool Photo via AP</a></span></figcaption></figure><p>“What happened this time was an ethics disaster for the world,” according to Wang Yuedan, a professor of immunology at Peking University, as <a href="https://www.nytimes.com/2018/11/30/world/asia/gene-editing-babies-china.html">quoted in The New York Times</a>. He was talking about the recent claim by U.S.-trained Chinese scientist He Jiankui that he’d successfully altered the DNA in vitro of human embryos that were later born as twin girls in China. If true as claimed, the edits he made would be inherited by any of their future offspring.</p>
<p>As a longtime <a href="https://scholar.google.com/citations?user=OBu0OHEAAAAJ&hl=en&oi=ao">scholar of international relations in science</a>, I contend the “disaster” has many more implications for China than the world at large.</p>
<p>No doubt, you’ve seen the news that a scientist at <a href="http://sustc.edu.cn/en/">Southern University of Science and Technology</a> in Shenzhen, China, created the <a href="https://theconversation.com/rogue-science-strikes-again-the-case-of-the-first-gene-edited-babies-107684">first human babies with changes to their genetic germline</a> — the genes the babies would pass on to their own children. The announcement was made <a href="https://theconversation.com/screening-the-human-future-youtube-persuasion-and-genetically-engineered-children-107938">in a most unorthodox way</a>: over social media rather than through accepted scientific channels of <a href="https://theconversation.com/peer-review-is-in-crisis-but-should-be-fixed-not-abolished-67972">peer review</a>, reproduction, validation and publication.</p>
<p>In turn, He has been hit by a furious backlash over perceived violations of <a href="https://theconversation.com/crispr-babies-raise-an-uncomfortable-reality-abiding-by-scientific-standards-doesnt-guarantee-ethical-research-108008">scientific and ethical norms</a>. But in this age of increasingly collaborative science, the furor could unleash repercussions throughout the Chinese research community – and perhaps even have an impact on China’s military strength.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/248585/original/file-20181203-194925-1tmbf6g.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/248585/original/file-20181203-194925-1tmbf6g.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/248585/original/file-20181203-194925-1tmbf6g.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/248585/original/file-20181203-194925-1tmbf6g.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/248585/original/file-20181203-194925-1tmbf6g.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/248585/original/file-20181203-194925-1tmbf6g.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/248585/original/file-20181203-194925-1tmbf6g.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/248585/original/file-20181203-194925-1tmbf6g.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The scientific enterprise is increasingly global and collaborative. Here He Jiankui elaborates on his announcement at the Second International Summit on Human Gene Editing in Hong Kong.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Hong-Kong-Gene-Edited-Babies/8143f99506f345d9a283afdb47db9de9/1/0">AP Photo/Kin Cheung</a></span>
</figcaption>
</figure>
<h2>Tarnished reputation and trustworthiness</h2>
<p>The disaster for China comes in several flavors.</p>
<p>One hit comes in the form of reputational damage in the international system of science and technology research. A researcher and their institution advance by gaining positive attention for their work. This social system operates globally and is driven by reputation. <a href="https://scholar.google.com/citations?user=YO5XSXwAAAAJ&hl=en&oi=ao">Jennifer Doudna</a>, the molecular biologist who first described CRISPR-Cas9, published with other top scientists in the journals Nature and Science, building a reputation that attracted elite collaborators. These collaborations, conducted across international lines, led to the <a href="https://doi.org/10.1126/science.1258096">critical CRISPR breakthrough</a>.</p>
<p>In a perverse way, He Jiankui seems to have bet on this dynamic — that by being first, he would enhance his own and his nation’s scientific reputation. He bet wrong. He may now join the pantheon of notables making claims through media rather than through science journals, such as chemists <a href="https://en.wikipedia.org/wiki/Fleischmann%E2%80%93Pons_experiment">Martin Fleischman and Stanley Pons</a>, who, in 1989, announced by <a href="http://newenergytimes.com/v2/reports/UniversityOfUtahPressRelease.shtml">press release</a> that they’d discovered fusion at room temperature. They had discovered something, but the work had not been validated by the community before they went public.</p>
<p>This rollout will not burnish China’s scientific reputation since the research community expects to be part of the conversation. Science requires openness and exchange; He Jiankui operated in secret.</p>
<p>He’s action introduced a second threat to China by further reducing international trust in scientific collaboration with his country. Even before He’s announcement, this trust has been challenged by a long string of missteps in science and technology that were easier to ignore when China was still a developing nation.</p>
<p>A group of American scholars recently issued <a href="https://www.hoover.org/research/chinese-influence-american-interests-promoting-constructive-vigilance">a warning, through a report</a> by Stanford University’s public policy think tank the Hoover Institution, that Chinese actions <a href="http://www.ipcommission.org/report/index.html">violating intellectual property rights</a> and international norms warrant stepping up “constructive vigilance” and backing away from cooperation. “At the same time that China’s authoritarian system takes advantage of the openness of American society to seek influence,” the document continues, “it impedes legitimate efforts by American counterpart institutions to engage Chinese society on a reciprocal basis.” </p>
<p>China has had a spectacular rise as a global scientific producer and partner. The U.S. National Science Foundation reported that, in 2016, the number of <a href="https://www.nsf.gov/news/news_summ.jsp?cntn_id=244271">Chinese scientific publications outnumbered those from the U.S.</a> for the first time. China has risen to become the number one partner of American scientists, supplanting the U.K. But its status as a scientific power and partner can only be damaged by He’s ethics violation. His research is another black mark against China, joining widespread <a href="https://www.nytimes.com/2017/10/13/world/asia/china-science-fraud-scandals.html">scientific plagiarism and fraud</a> and <a href="https://www.nytimes.com/2018/11/29/us/politics/china-trump-cyberespionage.html">industrial espionage</a>.</p>
<h2>The view from inside China’s military</h2>
<p><a href="https://www.scmp.com/news/china/military/article/2166260/chinese-military-crackdown-forged-data-and-plagiarism-science">China’s own military has warned</a> about the damaging implications of China’s lack of integrity in science scholarship. </p>
<p>More is at stake than just reputation. Over the past three centuries, no country has been a global political leader without corresponding leadership in science and technology. These two systems – military advancement and science and technology discovery – are symbiotically linked. As historians J. Rogers Hollingsworth and David Gear have pointed out, <a href="https://papers.ssrn.com/sol3/papers.cfm?abstract_id=2080318">advances in science and technology feed military strength</a>: military procurement, specification and demand vitalize scientific research and technological development. Science is most strenuously tested in frontier defense applications.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/248586/original/file-20181203-194935-1rsg6t1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/248586/original/file-20181203-194935-1rsg6t1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/248586/original/file-20181203-194935-1rsg6t1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/248586/original/file-20181203-194935-1rsg6t1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/248586/original/file-20181203-194935-1rsg6t1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/248586/original/file-20181203-194935-1rsg6t1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/248586/original/file-20181203-194935-1rsg6t1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/248586/original/file-20181203-194935-1rsg6t1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A Chinese child’s shoes, embroidered with the slogan ‘Those who invade my territory will be punished no matter how far away.’</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/China-Military/9b2a5566dbae4f7c98de49990fde2726/2/0">AP Photo/Ng Han Guan</a></span>
</figcaption>
</figure>
<p>Leadership in military capabilities appears to be China’s goal. So says a <a href="https://www.rand.org/pubs/research_reports/RR2588.html">RAND Corporation report</a> just this past month, along with <a href="https://www.bloomberg.com/opinion/articles/2018-06-10/china-s-master-plan-a-global-military-threat">others</a>. Although Premier Xi Jinping has written that China is committed to expanding involvement in the international system and the “<a href="http://www.chinadaily.com.cn/a/201807/17/WS5b4cf446a310796df4df6c54.html">open world economy</a>,” national actions suggest otherwise. China is investing in technologies that will challenge U.S. technological supremacy in artificial intelligence, supercomputing and quantum information systems, all of which will contribute to <a href="https://nationalinterest.org/blog/the-buzz/china-wants-the-most-powerful-military-the-planet-by-2050-24779">military strength</a>.</p>
<p>China will not attain its military goals without attendant leadership in science and technology. And in turn, leadership in science and technology today requires international collaboration, as I detail in my recent book, “<a href="https://www.palgrave.com/us/book/9783319949857">The Collaborative Era in Science</a>.” <a href="https://theconversation.com/how-fair-is-it-for-just-three-people-to-receive-the-nobel-prize-in-physics-85161">International collaborations</a> – especially those projects that achieve truly novel breakthroughs – require open cooperation, intense communication and a level of trust (often attached to reputation) that cannot be requisitioned with funds or forced by increasing the numbers of people working on it.</p>
<p>The collaborative era in science is a change from the historical conditions that nurtured the leadership of Britain, Germany, France and eventually the United States. In these earlier cases, leadership in both science and defense could be built at the national level. This is not the case for China. The globalized system, the abundance of knowledge and the openness of research practices means that nations cannot operate alone, as they once might have done, or as China might wish it could do.</p>
<p>So China’s inability to adhere to international ethical norms in the knowledge system ends up harming itself. A continued lack of collaborative spirit and practice will eventually deprive China and the world of its potential peaceful contributions. </p>
<p>A global system that works by reputation will shun those who do not play by the rules. Imitation and secrecy appear as fools gold to those who think they can close off and operate beyond the norms of 21st-century science. He Jiankui’s actions call into question whether China can be a good partner. This case of human gene editing leaves China viewed with wary skepticism by the rest of the world. It will be China’s choice going forward whether it can build a strong research system under the new rules of scientific collaboration.</p><img src="https://counter.theconversation.com/content/108009/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Caroline Wagner 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>In an era of big scientific collaborations, China’s renegade actions have hurt its reputation. As international researchers back away, it may be the country’s military that ultimately suffers.Caroline Wagner, Milton & Roslyn Wolf Chair in International Affairs, The Ohio State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1077642018-11-29T11:38:58Z2018-11-29T11:38:58ZHow a scientist says he made a gene-edited baby – and what health worries may ensue<figure><img src="https://images.theconversation.com/files/247748/original/file-20181128-32236-1golhuc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">He Jiankui, a Chinese researcher, speaks during the Human Genome Editing Conference in Hong Kong, Nov. 28, 2018. He made his first public comments about his claim of making the world's first gene-edited babies.</span> <span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Hong-Kong-Gene-Edited-Babies/147babf6ae11469f8c4e25361a5e97a0/12/0">AP Photo/Kin Cheung</a></span></figcaption></figure><p>On Nov. 28, He Jiankui claimed to a packed conference room at the <a href="http://www.nationalacademies.org/gene-editing/2nd_summit/index.htm">Second International Summit on Human Genome Editing</a> in Hong Kong to have edited the genomes of two twin girls, Lulu and Nana, who were born in China. </p>
<p>Scientists at Southern University of Science and Technology in Guangdong, China, <a href="https://theconversation.com/rogue-science-strikes-again-the-case-of-the-first-gene-edited-babies-107684">condemned He’s research</a> asserting he “<a href="http://sustc.edu.cn/en/info_focus/2871">has seriously violated academic ethics and codes of conduct</a>,” and philosophers and bioethicists were quick dive into the <a href="https://theconversation.com/the-road-to-enhancement-via-human-gene-editing-is-paved-with-good-intentions-107677">morass of editing human genomes</a>. So I’m not going to cover that territory. What I want to address is what we learned: how He made these babies. </p>
<p>I am theoretically a retired <a href="http://csu-cvmbs.colostate.edu/academics/bms/Pages/george-seidel.aspx">professor</a> in the Department of Biomedical Sciences at Colorado State University. For more than 50 years, I have researched numerous aspects of assisted reproductive technology including cloning and making genetic changes to mammalian embryos, so I am interested in most any research concerning “designer babies” and the health problems they may suffer. </p>
<h2>A first?</h2>
<p>At the conference He gave a general overview of the science. While research like this would typically be presented to the scientific community by publishing in a peer-reviewed journal, which He claims that he intends to do, we can get a rough sense of how he created these modified babies. This is something that has been successfully done in <a href="https://doi.org/10.1002/mrd.22812">other species</a> and just last year in <a href="https://doi.org/10.1038/nature23305">human embryos</a> – but the latter were not implanted into a woman. He says he spent three years testing the procedure on mice and monkeys before he moved to working on human embryos. </p>
<p>There is no doubt that precise genetic modifications can be made to human sperm, eggs, embryos and even some cells in adults. Such modifications have been done ad nauseum in <a href="https://doi.org/10.1038/s41591-018-0184-6">mice</a>, <a href="http://doi.org/10.1126/science.aan4187">pigs</a> and several other <a href="https://doi.org/10.1016/j.cell.2014.01.027">mammals</a>. Thus, it is obvious to scientists like myself that these same genetic modifications can, and will, be made in humans. The easiest way to make genetic changes begins with the embryo.</p>
<h2>The toolbox</h2>
<p>The trendiest strategy to modify DNA these days involves the CRISPR/Cas-9 gene editing tool, which can make precise genetic modifications in living cells. Although other tools have been available for years, the CRISPR/Cas-9 approach is simpler, easier, more accurate and less expensive.</p>
<p>The way it works is simple in concept. The Cas-9 component is a molecular scissors that cuts the DNA at the location specified by a small piece of RNA, called the “CRISPR template.” Once the DNA is cut, a gene can be modified at that location. The cut is then repaired by enzymes already present in cells.</p>
<p>In this case, He targeted a gene which produces a protein on the surface of cells called CCR5. The HIV virus uses this protein to attach to and infect the cell. He’s idea was to genetically change CCR5 so that HIV can no longer infect cells, making the girls resistant to the virus.</p>
<p>At this point He has not provided a clear explanation of exactly how he disabled the CCR5 and the nature of the genetic modification. But this kind of “disabling” is <a href="http://doi.org/10.1038/srep27810">routinely used in research</a>. </p>
<h2>How he did it</h2>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/247742/original/file-20181128-32185-t0ok1x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/247742/original/file-20181128-32185-t0ok1x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/247742/original/file-20181128-32185-t0ok1x.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/247742/original/file-20181128-32185-t0ok1x.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/247742/original/file-20181128-32185-t0ok1x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/247742/original/file-20181128-32185-t0ok1x.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/247742/original/file-20181128-32185-t0ok1x.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">He Jiankui presenting his data on Wednesday, Nov. 28, 2018. The Chinese researcher claims that he helped make the world’s first genetically edited babies.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Hong-Kong-Gene-Edited-Babies/a5b3fcf827cf490a80e4a139ad92e402/11/0">AP Photo/Kin Cheung</a></span>
</figcaption>
</figure>
<p>From the diagram He presented, it appears that He injected the CRISPR/Cas-9 system into an egg at the same time as he injected a sperm to fertilize it. After this, the egg divided and formed a ball of dozens of cells – the embryo. At this stage, He removed a few cells from each embryo to determine if the desired genetic change was made. Based on my experience, the embryos were probably frozen at this point. When the analysis was complete, He probably thawed the modified embryos and transferred the best ones back into the mother’s uterus for gestation to term. Embryos without the edits or incorrect edits would either be discarded or used for research.</p>
<p>For many applications, it is ideal to make any changes to the genes at the one-cell stage. Then, when the embryo duplicates its DNA and divides to make a two-cell embryo, the genetic modification is also duplicated. This continues so that every cell in the resulting baby has the genetic change. </p>
<p>However, it appears that the genetic modification in this case did not occur until the two-cell stage or later, because some cells in the babies had the modification, while others did not. This situation is called <a href="https://medlineplus.gov/ency/article/001317.htm">mosaicism</a> because the child is a mosaic of normal and edited cells. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/247777/original/file-20181128-32180-bzp7hb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/247777/original/file-20181128-32180-bzp7hb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/247777/original/file-20181128-32180-bzp7hb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/247777/original/file-20181128-32180-bzp7hb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/247777/original/file-20181128-32180-bzp7hb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/247777/original/file-20181128-32180-bzp7hb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/247777/original/file-20181128-32180-bzp7hb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/247777/original/file-20181128-32180-bzp7hb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">When the modified embryo has reached the multi-cell stage, one cell is removed and tested to confirm that the embryo carries the modification.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/extraction-embryonic-stem-cells-87760477?src=cs4UxTWmw1kqvGNOdqgL0Q-1-5">Juan Gaertner/Shutterstock.com</a></span>
</figcaption>
</figure>
<h2>Hazards of embryo editing?</h2>
<p>What could go wrong in a gene-edited embryo? Plenty. </p>
<p>The first glitch is that no modification was made, which occurs frequently. A variation is that the change occurs in some cells of the embryo, but not in all the cells, as occurred in these babies. </p>
<p>The most common worry is so-called non-target effects, in which the genetic modification is made, but other unintended edit(s) occur in other locations in the genome. Having a modification at the wrong place can cause all kinds of developmental problems, such as abnormal organ development, miscarriage and even cancers. </p>
<p>From his slide it appears that He sequenced the genomes – the complete genetic blueprint for each child – at multiple stages of the pregnancy to determine whether there were any undesirable modifications, though these aren’t always easy to find. But until independent scientists can examine the DNA of these two baby girls, we won’t know the results. It is also not clear from the results He has shared so far whether this genetic change can be transmitted to the next generation.</p>
<p>Another common problem already alluded to is mosaicism, which appears to have happened in one of these twins. If some cells are edited, and some not, the baby might have liver cells that contain the edited gene and heart cells that have the normal version, for instance. This may or may not lead to serious issues.</p>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/247791/original/file-20181128-32233-jkk38a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/247791/original/file-20181128-32233-jkk38a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/247791/original/file-20181128-32233-jkk38a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=543&fit=crop&dpr=1 600w, https://images.theconversation.com/files/247791/original/file-20181128-32233-jkk38a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=543&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/247791/original/file-20181128-32233-jkk38a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=543&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/247791/original/file-20181128-32233-jkk38a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=683&fit=crop&dpr=1 754w, https://images.theconversation.com/files/247791/original/file-20181128-32233-jkk38a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=683&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/247791/original/file-20181128-32233-jkk38a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=683&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Boy or Girl? You can already choose the sex of your baby.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/newborn-twin-babies-boy-girl-257910377">Hannamariah / Shutterstock.com</a></span>
</figcaption>
</figure>
<p>Another issue is that manipulating embryos in vitro – outside their normal environment in the reproductive tract – where we can’t precisely duplicate the normal nutrition, oxygen levels, hormones and growth factors – could lead to developmental abnormalities including oversize fetuses, metabolic problems, and so on. This sometimes occurs with routine procedures such as <a href="https://doi.org/10.1146/annurev-animal-022513-114109">in vitro fertilization</a> when there is no attempt to make genetic modifications. </p>
<p>Fortunately, nature is quite good at weeding out abnormal embryos via embryonic death and spontaneous abortion. Even in healthy human populations reproducing normally, <a href="https://www.webmd.com/baby/guide/pregnancy-miscarriage#1">nearly half of embryos die</a> before the woman even knows that she was pregnant. </p>
<h2>We already design babies – and there are benefits</h2>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/247782/original/file-20181128-32236-61x0lq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/247782/original/file-20181128-32236-61x0lq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/247782/original/file-20181128-32236-61x0lq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=367&fit=crop&dpr=1 600w, https://images.theconversation.com/files/247782/original/file-20181128-32236-61x0lq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=367&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/247782/original/file-20181128-32236-61x0lq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=367&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/247782/original/file-20181128-32236-61x0lq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=461&fit=crop&dpr=1 754w, https://images.theconversation.com/files/247782/original/file-20181128-32236-61x0lq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=461&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/247782/original/file-20181128-32236-61x0lq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=461&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">With in vitro fertilization, it is already possible to test the embryos to make sure they are free of inherited diseases like cystic fibrosis or Tay-Sachs syndrome and also to choose the sex of the baby.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/colored-vitro-fertilization-ivf-flat-infographics-1206548056">Macrovector / Shutterstock.com</a></span>
</figcaption>
</figure>
<p>While I have emphasized what can go wrong, I believe that the science will evolve such that genetically modified babies will be healthier than unmodified ones. And these improvements will be passed on to future generations. Severely debilitating genetic abnormalities such as <a href="https://ghr.nlm.nih.gov/condition/tay-sachs-disease">Tay-Sachs</a> syndrome could be removed from a family by genetic modification. </p>
<p>Arguably, designer babies are already being born using a technique called <a href="https://emedicine.medscape.com/article/273415-overview">pre-implantation genetic diagnoses (PGD)</a>. A few cells from embryos are screened for dozens, and potentially hundreds, of genetic abnormalities such as Down syndrome, cystic fibrosis and Tay-Sachs syndrome, to name a few. Parents are also able to choose those embryos of the desired sex. In my view, choosing which embryos to implant is clearly making designer babies.</p>
<p>Going a step further, PGD isn’t restricted to just eliminating disease. A prospective parent can also choose other traits. When one of the prospective parents in infertile, there are catalogs that provide the race, height and weight, and even the educational level of a sperm or egg donor, who is also determined to be free of major genetic defects, and free of AIDS and other venereal diseases. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/247780/original/file-20181128-32214-1dzhc62.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/247780/original/file-20181128-32214-1dzhc62.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/247780/original/file-20181128-32214-1dzhc62.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=432&fit=crop&dpr=1 600w, https://images.theconversation.com/files/247780/original/file-20181128-32214-1dzhc62.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=432&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/247780/original/file-20181128-32214-1dzhc62.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=432&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/247780/original/file-20181128-32214-1dzhc62.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=543&fit=crop&dpr=1 754w, https://images.theconversation.com/files/247780/original/file-20181128-32214-1dzhc62.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=543&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/247780/original/file-20181128-32214-1dzhc62.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=543&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">It is already possible to choose desirable traits in our offspring as this advertisement reveals: ‘Become a sperm donor today! We’re looking for a few good men!’</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/1010711809?src=SNF1ac8DDuBgYVpb_YMgWg-2-99&size=huge_jpg">Bilal Kocabas/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>In my opinion, if the procedures are deemed ethically and morally acceptable, most genetic modifications likely to be made editing embryos as He says he has done, will involve removal of harmful traits rather than adding desirable ones. Because the changes will be targeted, they will be more precise and less harmful than the mutations that occur randomly in DNA of essentially all sperm and eggs naturally.</p>
<p>With all of this reproductive technology, there is one other consideration: the huge costs of the procedures described. To what extent should society invest scarce medical resources in applying such techniques, especially since any benefits likely will accrue mostly to wealthier families? </p>
<p>These perspectives need to be kept in mind when evaluating potential genetic manipulations of humans.</p><img src="https://counter.theconversation.com/content/107764/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>I have been principal investigator for dozens of contracts and grants to Colorado State University from dozens of organizations between 1972 and 2013, the subject matter of which concerned assisted reproductive technologies. There has been no such activity during the last 5 years since I am technically retired.</span></em></p>Chinese researcher He Jiankui told a spellbound audience how he created gene-edited babies. With a couple of revealing slides, we can see what he did and speculate what health problems might ensue.George Seidel, Professor of Biomedical Sciences, Colorado State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1077562018-11-27T23:19:43Z2018-11-27T23:19:43ZWhy we are not ready for genetically designed babies<figure><img src="https://images.theconversation.com/files/247608/original/file-20181127-76746-1ons9mi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Any children born of genome editing are genetic mosaics with uncertain resistance to disease.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>The media is buzzing with the <a href="https://www.technologyreview.com/s/612458/exclusive-chinese-scientists-are-creating-crispr-babies/">surprise news</a> that a <a href="https://www.sciencemag.org/news/2018/11/crispr-bombshell-chinese-researcher-claims-have-created-gene-edited-twins">Chinese researcher, Jainkui He</a>, has <a href="https://www.apnews.com/4997bb7aa36c45449b488e19ac83e86d">created the world’s first genome-edited twins</a>. He did this, ostensibly, to provide resistance to HIV, the virus that causes AIDS.</p>
<p>Prof. He, reportedly working with former Rice University supervisor Michael Deem, capitalized on work in 2012 by Jennifer Doudna and Emmanuel Charpentier, who introduced a new and easier way of altering the DNA of human and non-human organisms using <a href="https://theconversation.com/beyond-just-promise-crispr-is-delivering-in-the-lab-today-77596">CRISPR-Cas9 technology</a>. He also built upon the work of molecluar biologist <a href="https://www.broadinstitute.org/bios/feng-zhang">Feng Zhang</a>, who optimized this genome editing system for use in human cells.</p>
<p>He’s claim moves human germline genome editing from the lab to the delivery room — something other scientists might have been thinking about despite <a href="https://impactethics.ca/2018/11/26/first-crispr-babies-where-are-our-ethics/">ethical concerns</a>. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/th0vnOmFltc?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Jainkui He explains why his lab edited the genome of twin baby girls, Nana and Lulu, when they were embryos.</span></figcaption>
</figure>
<p>The scientific community has expressed <a href="https://www.nature.com/articles/d41586-018-07545-0">widespread condemnation</a> of He’s decision to initiate a pregnancy using genetically modified embryos — as “dangerous, "irresponsible” and “crazy.” What if mistakes are made? How can we be sure this powerful technology will benefit humankind? Are we ready for the consequences of genetically engineering our own evolution?</p>
<p>We argue that we cannot allow individual scientists to decide the fate of the human genome. Heritable human genome editing poses a significant existential threat because changes may persist throughout the human population for generations, with unknown risks.</p>
<p>We must <a href="https://www.ctvnews.ca/health/you-can-t-pretend-to-be-god-experts-condemn-claimed-gene-editing-of-babies-1.4192563">commit to inclusive global dialogue</a> — involving experts and the public — to <a href="http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=12032015a">develop broad societal consensus on what to do with genetic technologies</a>.</p>
<h2>Possible mutations or forced sterilization</h2>
<p>He announced to the world that he edited the genome of human embryos for seven couples using CRISPR-Cas9 technology. According to He, two of these embryos resulted in a pregnancy, and twin girls (Lulu and Nana, which are pseudonyms) were born. </p>
<p>The goal of the editing was to confer resistance to HIV by modifying the CCR5 gene (the protein doorway by which HIV enters human cells). He claims that these edits have been verified in both twins and <a href="https://www.statnews.com/2018/11/26/claim-of-crispred-baby-girls-stuns-genome-editing-summit/">this data has been looked over and called “probably accurate</a>” by George Church, a world-renowned Harvard geneticist.</p>
<p>Evidence suggests, however, the procedure was unnecessary, is unlikely to provide benefit and could even cause harm. Although the father of Lulu and Nana was HIV positive, it is unlikely that he would have passed this disease to his children using standard IVF procedures. </p>
<p>The children born of genome editing are genetic mosaics with uncertain resistance to HIV and perhaps decreased resistance to viral diseases like influenza and West Nile. This is because the CCR5 gene that He disabled plays an important role in resistance to these diseases. </p>
<p>As well, there is the possibility of unintended mutations caused by the CRISPR procedure. These health risks cannot be overstated, as the repercussions for these twin girls, in terms of their susceptibility to infectious diseases or cancer will likely be a cause for concern throughout their lives. </p>
<p>Another uncertain consequence for the twins concerns their reproductive health and freedom. As they approach reproductive age will they face the possibility of “forced” sterilization to prevent their edited genes being passed on to future generations?</p>
<h2>Multiple investigations</h2>
<p>The Southern University of Science and Technology in Shenzhen, China, where He is employed (currently on leave from February 2018 to January 2021), has distanced itself from the researcher and will form an independent international committee to <a href="http://sustc.edu.cn/en/info_focus/2871">investigate the widely publicized, controversial research</a>. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/247599/original/file-20181127-76737-nyfwu8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/247599/original/file-20181127-76737-nyfwu8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/247599/original/file-20181127-76737-nyfwu8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/247599/original/file-20181127-76737-nyfwu8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/247599/original/file-20181127-76737-nyfwu8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=504&fit=crop&dpr=1 754w, https://images.theconversation.com/files/247599/original/file-20181127-76737-nyfwu8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=504&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/247599/original/file-20181127-76737-nyfwu8.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">Feng Zhang, center, an institute member of Harvard and MIT’s Broad Institute, reacts to reporters on the issue of world’s first genetically edited babies after the Human Genome Editing Conference in Hong Kong on Nov. 27, 2018.</span>
<span class="attribution"><span class="source">(AP Photo/Vincent Yu)</span></span>
</figcaption>
</figure>
<p>Rice University, where Michael Deem is employed, has also said <a href="https://www.statnews.com/2018/11/26/rice-university-opens-investigation-into-researcher-who-worked-on-crisprd-baby-project/">they will investigate</a>. </p>
<p>The Shenzhen HarMoniCare Women’s and Children’s Hospital launched an inquiry into the validity of the ethics documents provided by He documenting research ethics approval. </p>
<p>Importantly, the ethics approval was only uploaded to the Chinese Clinical Trial Database on Nov. 8 as a retrospective registration — likely around the time that the twins were purportedly born.</p>
<h2>Designer babies by powerful elites</h2>
<p>With the Genetic Genie out of the bottle, we have to ask whether we need any more time to reflect on the ethics?</p>
<p>A just and fair society is one with less disparity and more justice. A predictable consequence of allowing (nay, encouraging) individuals to genetically modify their children will be greater disparity and greater injustice — and not only because of limited access to genome editing technology. </p>
<p>Of significant concern is the inevitable increase in discrimination, stigmatization and marginalization as powerful scientific and corporate elites decide which traits are desirable and which traits are not. </p>
<p>Although He disavows any interest in so-called “designer babies” whose parents have chosen their children’s eye-colour, hair-colour, IQ and so on, we are forced to contemplate such a “eugenic” dystopian future should we continue down this path.</p>
<p>The human genome belongs to all of us. As such, we need to commit to the hard work of making good on the 2015 admonition by the Organizing Committee for the International Summit on Human Gene Editing to work towards <a href="http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=12032015a">“broad societal consensus”</a> on how we should proceed with, or not proceed with, editing it.</p>
<p>In this regard it is heartwarming to have <a href="https://www.technologyreview.com/s/612465/crispr-inventor-feng-zhang-calls-for-moratorium-on-baby-making/">Feng Zhang</a> call for a moratorium on implantation of edited embryos and remind his scientific colleagues that “in 2015, the international research community said it would be irresponsible to proceed with any germline editing without ‘broad societal consensus about the appropriateness of the proposed application.’”</p><img src="https://counter.theconversation.com/content/107756/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Françoise Baylis has received funding from the Canadian Institute of Health Research and the Canada Research Chairs Program.</span></em></p><p class="fine-print"><em><span>Graham Dellaire receives funding from the Canadian Institutes of Health Research (CIHR).</span></em></p><p class="fine-print"><em><span>Landon J Getz receives funding from the Natural Sciences and Engineering Research Council of Canada. </span></em></p>Chinese researcher, Jainkui He claims to have created the world’s first genome-edited twins. Such action would pose unknown risks to the lives of these children and to humanity as a whole.Françoise Baylis, Research Professor, Philosophy, Dalhousie UniversityGraham Dellaire, Director of Research and Professor of Pathology, Dalhousie UniversityLandon J Getz, Vanier Scholar and Ph.D. Candidate in Microbiology and Immunology, Dalhousie UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1076842018-11-27T15:13:11Z2018-11-27T15:13:11ZRogue science strikes again: The case of the first gene-edited babies<figure><img src="https://images.theconversation.com/files/247537/original/file-20181127-76764-sd4z6m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Chinese scientists led by He Jiankui claimed they used CRISPR to modify human embryos that eventually were born as twin girls.</span> <span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Genetic-Frontiers-Gene-Edited-Babies/357555b59c0a41fb93a35eb0a938a38d/4/0">AP Photo/Mark Schiefelbein</a></span></figcaption></figure><p>The idea of scientists tinkering with the genes of babies was once the provenance of science fiction, but now it’s apparently entered the realm of reality: On Nov. 26, Chinese scientist He Jiankui reported the historic live births of <a href="https://www.apnews.com/4997bb7aa36c45449b488e19ac83e86d">twin girls whose genes he had edited</a>. The goal <a href="https://theconversation.com/the-road-to-enhancement-via-human-gene-editing-is-paved-with-good-intentions-107677">may have been noble</a>: to use CRISPR to alter their genes to include a variant protective against transmission of HIV. But the announcement – yet to be verified – has quickly become mired in a deluge of scientific and ethical <a href="https://theconversation.com/worlds-first-gene-edited-babies-premature-dangerous-and-irresponsible-107642">criticism</a> of He as a reckless researcher who overstepped well-established boundaries.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/247539/original/file-20181127-76764-1679rlk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/247539/original/file-20181127-76764-1679rlk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/247539/original/file-20181127-76764-1679rlk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/247539/original/file-20181127-76764-1679rlk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/247539/original/file-20181127-76764-1679rlk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/247539/original/file-20181127-76764-1679rlk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/247539/original/file-20181127-76764-1679rlk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/247539/original/file-20181127-76764-1679rlk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">He Jiankui has a lot to explain going forward.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Genetic-Frontiers-Gene-Edited-Babies/c5f8eb88e0e64fc3aed2b2388e0195ff/1/0">AP Photo/Mark Schiefelbein</a></span>
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<h2>Professional outcry</h2>
<p>The reaction from the professional community of scientists and ethicists was swift and essentially universal in its condemnation, including by <a href="https://qz.com/1474530/chinese-scientists-condemn-crispr-baby-experiment-as-crazy/">over 100</a> of He’s colleagues in China.</p>
<p>A <a href="https://theconversation.com/worlds-first-gene-edited-babies-premature-dangerous-and-irresponsible-107642">central objection</a> is that the study was simply too risky. Researchers have stressed that the risk of off-target effects (unintentionally changing other genes) and mosaicism (only altering the target gene in some of the child’s cells rather than all of them) could lead to <a href="https://www.newscientist.com/article/2174149-crispr-gene-editing-is-not-quite-as-precise-and-as-safe-as-thought/">unexpected and harmful health effects</a> such as cancer later in life. There is general agreement that <a href="https://theconversation.com/heres-what-we-know-about-crispr-safety-and-reports-of-genome-vandalism-100231">at present these risks</a> outweigh any potential benefits, and more basic research is needed before proceeding.</p>
<p>Interestingly, some of the strongest ethical objections to the experiment came from ethicists who have in other venues defended gene editing. <a href="https://scholar.google.com/citations?user=PxdgzQUAAAAJ&hl=en&oi=ao">Julian Savulescu</a>, for example, has <a href="https://www.sciencenews.org/blog/science-public/ethics-gene-editing-babies-crispr">gone so far as to argue</a> that, if it were safe and not too costly, we would even have an obligation to edit our children’s genes. Yet <a href="http://blog.practicalethics.ox.ac.uk/2018/11/press-statement-monstrous-gene-editing-experiment/">he called</a> the reported experiment “monstrous,” in light of the serious risks and lack of necessity. The twins were never in danger of inheriting a deadly genetic disorder, and there are far less risky ways to prevent HIV transmission.</p>
<h2>Public perception</h2>
<p>This backlash may have caught He by surprise. According to one report, He commissioned a <a href="https://www.technologyreview.com/s/612458/exclusive-chinese-scientists-are-creating-crispr-babies/">large-scale public opinion survey in China</a> a few months prior to the announcement. The survey found that over <a href="http://scd.sysu.edu.cn/sites/scd.prod.dpweb3.sysu.edu.cn/files/2018-11/ChinesePublicAttitudesOnGeneEditing.pdf">70 percent of the Chinese public was supportive</a> of using gene editing for HIV prevention. This is <a href="http://www.pewinternet.org/2018/07/26/public-views-of-gene-editing-for-babies-depend-on-how-it-would-be-used/">roughly in line</a> with a recent Pew poll in the United States that found 60 percent of Americans support using gene editing on babies to reduce lifetime risk of contracting certain diseases.</p>
<p>But polling tells only part of the story. The same Chinese poll also found very low levels of public understanding of gene editing and did not mention the details of He’s study. Abstract polling questions ignore the risks and state of the science, which were crucial to most objections to He’s experiment. It also obscures the involvement of embryos in gene editing. In the American Pew poll, despite overall support for gene editing, 65 percent opposed embryonic testing – a necessary step in the process of gene editing to address disease.</p>
<p>Moreover, polling is a crude and simplistic way to engage in public debate and deliberation over the controversial issue of gene editing. Various bodies, such as the <a href="https://www.nap.edu/read/24623/chapter/1">National Academies of Sciences, Medicine and Engineering</a> in the U.S. and the <a href="http://nuffieldbioethics.org/wp-content/uploads/Genome-editing-and-human-reproduction-short-guide-website.pdf">Nuffield Council on Bioethics</a> in the U.K., have emphasized that, for gene editing to proceed to human trials, a robust public discussion is first needed to establish its legitimacy.</p>
<p>Yet He decided to proceed in the least transparent way possible, hiding his study from public view, colleagues and his institution, and even going so far as to <a href="http://www.sustc-genome.org.cn/source/pdf/Informed-consent-women-English.pdf">ban participants</a> from sharing with anyone their participation in the trial, on pain of financial penalty.</p>
<p>He’s recklessness, then, was not limited to risk but also failing to earn public trust and buy-in before proceeding.</p>
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<a href="https://images.theconversation.com/files/247541/original/file-20181127-76746-1xpfw30.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/247541/original/file-20181127-76746-1xpfw30.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/247541/original/file-20181127-76746-1xpfw30.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/247541/original/file-20181127-76746-1xpfw30.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/247541/original/file-20181127-76746-1xpfw30.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/247541/original/file-20181127-76746-1xpfw30.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/247541/original/file-20181127-76746-1xpfw30.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/247541/original/file-20181127-76746-1xpfw30.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">IVF can be prohibitively expensive, even without editing the embryos’ genes.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Genetic-Frontiers-Gene-Edited-Babies/be12da8f5c424f18b43be98f34b4545f/3/0">AP Photo/Mark Schiefelbein</a></span>
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<h2>Consent and inducement</h2>
<p>A further failing of He’s experiment was the consent process. The study recruited couples with an HIV-positive husband and HIV-negative wife. Ostensibly, the couples had a particular interest in ensuring their children never contracted HIV, in light of the intended father’s experience. But looking a little closer reveals other, more problematic motivations.</p>
<p>For such couples, it is possible to safely conceive an HIV-negative child using <a href="https://academic.oup.com/humrep/article/22/3/772/2939095">robust IVF procedures</a>. Such therapy is expensive, prohibitively so for many couples. But He’s study offered a particularly enticing carrot – free IVF treatment and supportive care, along with a daily allowance and insurance coverage during the treatment and pregnancy. According to the <a href="http://www.sustc-genome.org.cn/source/pdf/Informed-consent-women-English.pdf">consent form</a>, the total value of treatments and payments was approximately US$40,000 – over four times the <a href="https://www.statista.com/statistics/278349/average-annual-salary-of-an-employee-in-china/">average annual wage</a> in urban China.</p>
<p>This raises a serious concern of <a href="https://www.dovepress.com/bioethical-issues-in-providing-financial-incentives-to-research-partic-peer-reviewed-fulltext-article-MB">undue inducement</a>: paying research participants such a large sum that it distorts their assessment of the risks and benefits. In this gene editing context, where the risks are incredibly uncertain and there is substantially limited general understanding of genetics and gene editing, society should be especially concerned about the distorting effect of such a large reward on the participants’ provision of free and informed consent.</p>
<h2>Aftermath</h2>
<p>In a <a href="https://www.youtube.com/watch?v=th0vnOmFltc&t=140s">video</a> announcing the birth of the twins, He announced he was willing to take on all personal responsibility for the conduct and outcomes of the experiment. And indeed, the consequences of this unethical experiment are already piling up. His own university has disavowed him, having previously suspended him, while <a href="https://www.technologyreview.com/s/612466/the-chinese-scientist-who-claims-he-made-crispr-babies-has-been-suspended-without-pay/">multiple investigations</a> are being launched into He, his <a href="https://www.statnews.com/2018/11/26/rice-university-opens-investigation-into-researcher-who-worked-on-crisprd-baby-project/">American collaborator</a> and the hospital ethics committee that approved the experiment. </p>
<p>The outcome of those investigations remains to be seen, but it is part of a disturbing pattern in reproduction: rogue scientists bucking international norms to engage in ethically and scientifically dubious reproductive research. Indeed, just within the last two years another set of <a href="https://www.newscientist.com/article/2107219-exclusive-worlds-first-baby-born-with-new-3-parent-technique/">renegade</a> <a href="https://www.npr.org/sections/health-shots/2018/06/06/615909572/inside-the-ukrainian-clinic-making-3-parent-babies-for-women-who-are-infertile">scientists</a> flaunted established norms to bring about the first “three-parent IVF” babies; there was tremendous outcry, but the procedure now seems to be continuing in the relatively lax regulatory environment of Ukraine. </p>
<p>Hard work is now needed by scientists, ethicists, policymakers and the public at large to figure out how to reverse this trend and return reproductive medicine to a path of responsible research and innovation.</p><img src="https://counter.theconversation.com/content/107684/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 announcement of the birth of babies with edited genes has been met by a deluge of scientific and ethical criticism. Public discussion focuses on risks and benefits – was breaking this taboo worth it?G. Owen Schaefer, Research Assistant Professor in Biomedical Ethics, National University of SingaporeLicensed as Creative Commons – attribution, no derivatives.