tag:theconversation.com,2011:/us/topics/germline-editing-18978/articlesGermline editing – The Conversation2023-03-08T12:06:26Ztag:theconversation.com,2011:article/2009832023-03-08T12:06:26Z2023-03-08T12:06:26ZHuman genome editing offers tantalizing possibilities – but without clear guidelines, many ethical questions still remain<figure><img src="https://images.theconversation.com/files/513790/original/file-20230306-28-k1tc0y.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1936%2C1547&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">DNA editing has the capacity to treat many diseases, but how to do this safely and equitably remains unclear.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/molecules-illustration-royalty-free-image/1148113002">KTSDESIGN/Science Photo Library via Getty Images</a></span></figcaption></figure><p><a href="https://royalsociety.org/science-events-and-lectures/2023/03/2023-human-genome-editing-summit/">The Third International Summit on Human Genome Editing</a>, a three-day conference organized by the Royal Society, the U.K. Academy of Medical Sciences, the U.S. National Academies of Sciences and Medicine and The World Academy of Sciences, was held this week in March 2023 at the Francis Crick Institute in London. Scientists, bioethicists, physicians, patients and others gathered to discuss the latest developments on this technology that lets researchers modify DNA with precision. And a major topic at the summit was <a href="https://royalsociety.org/-/media/events/2023/03/human-genome-editing-summit/third-international-summit-on-human-genome-editing-programme-booklet.pdf?la=en-GB&hash=16DB894FBD02A549B2F090D575C3E92D">how to enforce</a> research policies and ethical principles for human genome editing.</p>
<p>One of the first agenda items was how to regulate human genome editing in China in light of its <a href="https://theconversation.com/crispr-babies-raise-an-uncomfortable-reality-abiding-by-scientific-standards-doesnt-guarantee-ethical-research-108008">misuse in 2018</a>, when scientists modified the DNA of two human embryos before birth to have resistance against HIV infection. The controversy stems from the fact that because the technology is relatively early in its development, and its potential risks have not been reduced or eliminated, editing human embryos in ways they could pass on to their own offspring could lead to a variety of known and unknown adverse complications. The <a href="https://www.statnews.com/2023/03/06/genome-editing-summit-experts-worry-rule-changes-in-china-fall-short/">summit speakers noted</a> that while China has updated its guidelines and laws on human genome editing, it failed to address privately funded research – an issue other countries also face. Many countries, including the U.S., <a href="https://doi.org/10.1038/d41586-023-00625-w">do not have sufficiently robust regulatory frameworks</a> to prevent a repeat of the 2018 scandal.</p>
<p>We are a <a href="https://www.rit.edu/hudsonlab/">biochemist</a> and a <a href="https://www.rit.edu/directory/grssbi-gary-skuse">geneticist</a> who teach and conduct research in genomics and ethics at the Rochester Institute of Technology. As in our classrooms, debate about genome editing continues in the field.</p>
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<figcaption><span class="caption">Listening to different perspectives about CRISPR could lead to more balanced discussions about how to regulate it.</span></figcaption>
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<h2>What is genome editing?</h2>
<p>The <a href="https://theconversation.com/the-human-genome-project-pieced-together-only-92-of-the-dna-now-scientists-have-finally-filled-in-the-remaining-8-176138">human genome</a> typically consists of 23 pairs of chromosomes made of approximately 3.2 billion nucleotides – the building blocks of DNA. There are four nucleotides that make up DNA: adenine (A), thymine (T), guanine (G) and cytosine (C). If the genome were a book, each chromosome would be a chapter, each gene on a particular chromosome would be a paragraph and each paragraph would be made of individual letters (A, T, G or C). </p>
<p>One can imagine a book with over 3 billion characters might need editing to correct mistakes that occurred during the writing or copying processes. </p>
<p>Genome editing is a way for scientists to make specific changes to the DNA in a cell or in an entire organism by adding, removing or swapping in or out one or more nucleotides. In people, these changes can be done in somatic cells, those with DNA that cannot be inherited by offspring, or in gamete cells, those containing DNA that can be passed on to offspring. Genome editing of gamete cells, which includes egg or sperm, is controversial, as any changes would be passed on to descendants. Most <a href="https://doi.org/10.1089/crispr.2020.0082">existing guidelines and policies</a> prohibit its use at this time.</p>
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<figcaption><span class="caption">Geneticist Jennifer Doudna is one of the co-inventors of CRISPR/Cas9.</span></figcaption>
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<h2>How CRISPR works</h2>
<p>In 2012, scientists published a <a href="https://doi.org/10.1126/science.1225829">groundbreaking study</a> demonstrating how CRISPR, or Clustered Regularly Interspaced Short Palindromic Repeats, can be used to accurately change specific DNA sequences.</p>
<p>CRISPR’s natural origins are as a kind of immune response for bacteria. Bacteria that can be infected with viruses have evolved mechanisms to combat them. When a bacterium is infected with a particular virus, it keeps a small piece of the viral DNA sequence called a “spacer” in its own genome. This spacer is an exact match to the viral DNA. Upon subsequent infection, the bacterium is able to use the spacer to recruit a scissorlike protein called Cas9 that can sever new viral DNA attempting to integrate into the bacterium’s genome. This cut to the genetic material prevents the virus from replicating and killing its bacterial host.</p>
<p>After this discovery, scientists were able to fine-tune the system in the lab to be highly precise. They can sever DNA from a variety of cells, including human cells, at a specific location in the genome and subsequently edit it by adding, removing or swapping nucleotides. This is similar to adding or removing letters and words from a book. </p>
<p>This technology has the potential to treat diseases that have genetic origins. One of the summit’s sessions covered CRISPR’s ongoing experimental use to treat patients with <a href="https://doi.org/10.1056/NEJMoa2031054">sickle cell anemia and beta-thalassemia</a>, two blood disorders caused by mutations in the genes. Notably, genetic modification to treat sickle cell anemia and beta-thalassemia involves editing somatic cells, not germline cells. But as the summit speakers noted, whether these likely expensive therapies will be <a href="https://www.statnews.com/2023/03/07/crispr-sickle-cell-access/">accessible to the people who need them most</a>, especially in low- and middle-income countries, is a problem that requires changes to how treatments are sold.</p>
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<figcaption><span class="caption">Scientists have been testing ways to use CRISPR/Cas9 to treat sickle cell anemia.</span></figcaption>
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<h2>Ethics of human genome editing</h2>
<p><a href="https://doi.org/10.1016%2Fj.jmb.2018.05.044">Many questions remain</a> concerning the safety of genome editing, along with its potential to promote eugenics and exacerbate inequities and inequality.</p>
<p>A number of the summit’s sessions involved discussion on the ethics and regulation of the use of this tool. While the landmark 1979 <a href="https://www.hhs.gov/ohrp/regulations-and-policy/belmont-report/read-the-belmont-report/index.html">Belmont Report</a> outlined several ethical pillars to guide human research in the U.S., it was published before human genome editing was developed. In 2021, the World Health Organization <a href="https://www.who.int/news/item/12-07-2021-who-issues-new-recommendations-on-human-genome-editing-for-the-advancement-of-public-health">issued recommendations on human genome editing</a> as a tool to advance public health. There is <a href="https://doi.org/10.1146/annurev-genom-111320-091930">no current international law</a> governing human genome editing. </p>
<p>There is <a href="https://www.pewresearch.org/internet/2022/03/17/americans-are-closely-divided-over-editing-a-babys-genes-to-reduce-serious-health-risk/">still a debate</a> regarding how to use this technology. Some people equate genome editing to interfering with the work of God and argue that it shouldn’t be used at all, while others recognize its potential value and weigh that against its potential risks. The latter focuses on the fundamental question of <a href="https://www.scientificamerican.com/article/the-dark-side-of-crispr/">where to draw the line</a> between which applications are considered acceptable and which are not. For example, some people will agree that using genome editing to modify a defective gene that may lead to an infant’s death if untreated is acceptable. But these same people may frown upon the use of genome editing to ensure that an unborn child has specific physical features such as blue eyes or blond hair.</p>
<p>Nor is there consensus about <a href="https://doi.org/10.1001/jama.2022.13468">what diseases</a> are desirable targets. For example, it may be acceptable to modify a gene to prevent an infant’s death but not acceptable to modify one that prevents a disease later in life, such as the gene responsible for <a href="https://www.mayoclinic.org/diseases-conditions/huntingtons-disease/symptoms-causes/syc-20356117">Huntington’s disease</a>.</p>
<p>The potential for positive applications of human genome editing is both numerous and tantalizing. But establishing informed regulatory legislation everyone can agree on is and will continue to be a challenge. Conferences such as the human genome editing summit are one way to continue important discussions and educate the scientific community and the public on the benefits and risks of genome editing.</p><img src="https://counter.theconversation.com/content/200983/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andre Hudson receives funding from the National Institutes of Health</span></em></p><p class="fine-print"><em><span>Gary Skuse has received funding from the National Science Foundation. </span></em></p>Following the controversial births of the first gene-edited babies, a major focus of the Third International Summit on Human Genome Editing was responsible use of CRISPR.André O. Hudson, Interim Dean/Professor-College of Science, Rochester Institute of TechnologyGary Skuse, Professor of Bioinformatics, Rochester Institute of TechnologyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1491082021-02-15T14:31:11Z2021-02-15T14:31:11ZFive principles that should guide future DNA ‘editing’ in South Africa<figure><img src="https://images.theconversation.com/files/380676/original/file-20210126-15-1ertiyg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Any man-made changes to the human genome must be carefully regulated.</span> <span class="attribution"><span class="source">Billon Photos/Shutterstock</span></span></figcaption></figure><p>In recent years there have been several major innovations in genetics. One prominent example is <a href="https://theconversation.com/what-is-crispr-the-gene-editing-technology-that-won-the-chemistry-nobel-prize-147695">CRISPR-Cas9</a>, a novel biotechnology derived from bacteria that could be used to make precise changes to specific locations in the human genome – our DNA. </p>
<p>Scientists could use CRISPR-Cas9 and similar technologies to eliminate genetic diseases by using germline cells (gametes and embryos). This is known as germline editing; a child born from modified gametes or embryos will have such “edits” in their DNA and can pass those on to their future offspring. Of course, as with anything that relates to altering DNA, <a href="http://sajbl.org.za/index.php/sajbl/article/viewFile/636/626">controversy abounds</a>.</p>
<p>It is possible that germline editing will be ready for public use in the next decade. Currently, however, many <a href="https://doi.org/10.1186/1477-7827-12-108">countries lack rules on the use of this technology</a>. Therefore, it has been argued that this situation should be rectified to ensure that germline editing is governed by proper legal and ethical rules, although what these rules should be is heavily disputed.</p>
<p>In a <a href="https://www.sajs.co.za/article/view/6760">recent paper</a> published by the South African Journal of Science, we investigated the current regulatory framework for germline editing in South Africa. Quite simply, it is lacking and several gaps must be filled. We propose five principles that could guide a proper ethical and legal framework for this and similar technologies.</p>
<h2>The status quo</h2>
<p>There is a distinction between the rules relating to germline editing by scientists for the purpose of research, and germline editing for use in practice by the general public, known as clinical application.</p>
<p>South Africa’s regulatory environment that covers questions of ethics in medicine currently seems to not permit research on, and the clinical application of, human germline editing. This is according to ethics guidelines published by the <a href="https://www.sada.co.za/media/documents/HPCSA_Booklet_14_Biotechnology_Research_in_SA.pdf">Health Professions Council of South Africa</a> and the <a href="https://www.samrc.ac.za/sites/default/files/attachments/2016-06-29/ethicsbook2.pdf">South African
Medical Research Council</a> – although the justifications for this are unclear. </p>
<p>By contrast, the South African legal regulatory environment allows a regulatory path that would, in principle, permit research on human germline editing. This is because none of the current regulation on research using germline cells prohibits research for the purpose of germline editing. The legal regulation of the clinical application of human germline editing, on the other hand, is uncertain. </p>
<p>When it comes to research, there is currently no South African law that specifically regulates germline editing. It’s expected to comply with the same laws and ethical requirements as <a href="https://www.sajs.co.za/article/view/6760">all scientific research relating to human reproduction.</a>. This gap needs to be addressed through new regulations.</p>
<p>When it comes to germline editing as a clinical application, new regulations are required. But the wording will need to be nuanced because germline editing has long term, multi-generational effects that must be taken into account.</p>
<p>The new regulation will also have to manage gaps such as the fact that the practice is viewed under existing regulations as a hybrid of medicine and medical device.</p>
<p>Crucially, germline editing can only proceed if South African law doesn’t prohibit it. Some may argue that section 57 of the <a href="https://www.gov.za/documents/national-health-act">National Health Act</a>, which forbids the “reproductive cloning of a human being”, applies here – and so, they would suggest, germline editing is actually illegal. </p>
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Read more:
<a href="https://theconversation.com/why-the-case-against-designer-babies-falls-apart-45256">Why the case against designer babies falls apart</a>
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<p>But we disagree with this line of argument. This provision was intended for the purpose of regulating cloning, and because germline editing is different from cloning, this section should not be interpreted as applying to germline editing. </p>
<p>Having considered all this, we propose that five guiding principles should steer future regulation of germline editing in South Africa.</p>
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Read more:
<a href="https://theconversation.com/human-gene-editing-who-decides-the-rules-128434">Human gene editing: who decides the rules?</a>
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<h2>Principles</h2>
<p><strong>Principle 1: Human germline editing should be regulated, not banned.</strong></p>
<p>Human germline editing for clinical application has the potential to improve people’s lives. It could, for instance, be used to prevent diseases. For this reason, it shouldn’t be ignored or banned; instead proper regulation that considers the potential long-term implications must be considered.</p>
<p><strong>Principle 2: Use the well-established standard of safety and efficacy.</strong> </p>
<p>Human germline editing clinical applications should only be made accessible to the public if they are proven to be safe and effective, including for future generations. This will mean that human clinical trials will have to be carried out. These are <a href="https://doi.org/10.1007/s11673-019-09947-9">challenging, but possible</a>.</p>
<p><strong>Principle 3: Non-therapeutic uses of germline editing may be permissible.</strong></p>
<p>Even among those who are in favour of germline editing, it is often claimed that such use should be limited exclusively to the ‘therapeutic’ in the form of preventing genetic diseases. This, <a href="http://sajbl.org.za/index.php/sajbl/article/viewFile/636/626">it is said</a>, makes it different from genetic ‘enhancement’ in the form of germline edits that are not done for the purpose of healing people, but benefiting them. An example of genetic enhancement would be an edit which made a child have a high IQ or greater athletic ability. </p>
<p>These are often viewed as morally reprehensible because they <a href="https://academic.oup.com/jlb/article/5/2/355/5036208">are reminiscent of the state-sponsored eugenics programmes</a> of early 20th century Britain, America and Nazi Germany. </p>
<p>It is important to note that state-enforced eugenic regimes used coercive means that violated procreative freedom. But individual uses of germline editing technologies promote procreative freedom by leaving their application up to individual choice. </p>
<p><strong>Principle 4: Respect parents’ reproductive autonomy.</strong></p>
<p>The choice to use safe and effective germline editing should be made by individual prospective parents because this choice is part of the parents’ right to make decisions concerning reproduction. The freedom to use new reproductive technologies like germline editing is one which falls under the protection of section 12(2)(a) of South Africa’s <a href="https://www.justice.gov.za/legislation/constitution/SAConstitution-web-eng.pdf">Constitution</a>. </p>
<p><strong>Principle 5: Promote the achievement of equality of access.</strong></p>
<p>New technology may only be accessible to the rich, worsening existing inequalities in society – particularly in societies like South Africa given the wide <a href="https://theconversation.com/south-africa-needs-to-fix-its-dangerously-wide-wealth-gap-66355">gap between the rich and poor</a>, and the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556866/">lack of access to healthcare</a> for the underprivileged. However, the possibility of inequality cannot be a reason to suppress the technology. Instead it should be a reason for measures to be taken that promote access for the underprivileged.</p><img src="https://counter.theconversation.com/content/149108/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Bonginkosi Shozi receives funding from the National Research Foundation and the UKZN African Health Research Flagship. </span></em></p><p class="fine-print"><em><span>Marietjie Botes receives funding from the UKZN African Health Law Research Flagship</span></em></p>We propose five principles that could guide a proper ethical and legal framework for germline editing and similar technologies.Bonginkosi Shozi, Doctoral Fellow with the UKZN African Health Research Flagship, University of KwaZulu-NatalMarietjie Botes, Post Doctoral Fellow, University of KwaZulu-NatalLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1513132020-12-07T13:24:31Z2020-12-07T13:24:31ZEditing the DNA of human embryos could protect us from future pandemics<figure><img src="https://images.theconversation.com/files/373292/original/file-20201207-15-iedm1d.jpg?ixlib=rb-1.1.0&rect=60%2C60%2C6720%2C4365&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">We could edit our genes to make us more resistance to viruses.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/researcher-working-dna-on-blurred-background-1106986568"> Natali_ Mis/Shutterstock</a></span></figcaption></figure><p>Hollywood blockbusters such as <a href="https://www.imdb.com/title/tt0120903/">X-men</a>, <a href="https://www.imdb.com/title/tt0119177/">Gattaca</a> and <a href="https://www.imdb.com/title/tt0369610/">Jurassic World</a> have explored the intriguing concept of “germline genome editing” – a biomolecular technique that can alter the DNA of sperm, eggs or embryos. If you remove a gene that causes a certain disease in an embryo, not only will the baby be free of the disease when born – so will its descendants. </p>
<p>The technique is, however, controversial – we can’t be sure how a child with an altered genome will develop over a lifetime. But with the COVID-19 pandemic showing just how vulnerable human beings are to disease, is it time to consider moving ahead with it more quickly?</p>
<p>There’s now good evidence that the technique works, with research normally carried out on unviable embryos that will never result in a living baby. But in 2018, Chinese scientist He Jiankui claimed that the first gene-edited babies <a href="https://www.ncbi.nlm.nih.gov/books/NBK535994/">had indeed been born</a> – to the <a href="https://theconversation.com/worlds-first-gene-edited-babies-premature-dangerous-and-irresponsible-107642">universal shock</a>, criticism and intrigue of the scientific community.</p>
<p>This human germline genome editing (hGGe) was performed using the <a href="https://theconversation.com/nobel-prize-two-women-share-chemistry-prize-for-the-first-time-for-work-on-genetic-scissors-147721">Nobel-prize winning CRISPR system</a>, a type of molecular scissors that can cut and alter the genome at a precise location. Researchers and policy makers in the fertility and embryology space agree that it is a matter of “when” and not “if” hGGe technologies will become available to the general public.</p>
<p>In 2016, the UK became the first country in the world to formally permit “<a href="https://theconversation.com/worlds-first-three-parent-baby-raises-questions-about-long-term-health-risks-66189">three-parent babies</a>” using a genetic technique called mitochondrial replacement therapy – replacing unhealthy mitochondria (a part of the cell that provides energy) with healthy ones from a donor.</p>
<h2>COVID-19 protection</h2>
<p>Scientists are now discussing genome editing <a href="https://www.wired.com/story/could-crispr-be-the-next-virus-killer/">in the light of the
COVID-19 pandemic</a>. For example, one could use CRISPR <a href="https://www.fiercebiotech.com/research/stanford-team-deploys-crispr-gene-editing-to-fight-covid-19">to disable coronaviruses</a> by scrambling their genetic code. But we could also edit people’s genes to make them more resistant to infection – for example by targeting “T cells”, which are central in the body’s immune response. There are already CRISPR clinical trials underway that look to <a href="https://science.sciencemag.org/content/367/6481/eaba7365">genome edit T cells in cancer patients</a> to improve anti-tumour immunity (T cells attacking the tumour). </p>
<p>This type of gene editing differs to germline editing as it occurs in non-reproductive cells, meaning genetic changes are not heritable. In the long term, however, it may be more effective to improve T-cell responses using germline editing.</p>
<p>It’s easy to see the allure. The pandemic has uncovered the brutal reality that the majority of countries across the world are completely ill equipped to deal with sudden shocks to their, often, already overstretched healthcare systems. Significantly, the healthcare impacts are not only felt on COVID patients. Many cancer patients, for instance, have struggled to access treatments or diagnosis appointments in a timely manner during the pandemic.</p>
<p>This also raises the possibility of using hGGe techniques to tackle serious diseases such as cancer to protect healthcare systems against future pandemics. We already have a wealth of information that suggests certain gene mutations, such as those in the BRCA2 gene in women, increase the probability of cancer development. These disease genetic hotspots <a href="https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet">provide potential targets</a> for hGGe therapy. </p>
<p>Furthermore, healthcare costs for diseases such as cancer will continue to rise as drug therapies continue to become more personalised and targeted. At this point, wouldn’t gene editing be simpler and cheaper? </p>
<h2>Climate change and malaria</h2>
<p>As we approach the mezzo point of the 21st century, it is fair to say that COVID-19 could prove to be just the start of a string of international health crises that we encounter. A <a href="https://ipbes.net/pandemics">recent report</a> by the UN Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) emphasised the <a href="https://theconversation.com/why-are-emerging-viruses-here-and-why-now-29311">clear connection</a> between global pandemics and the loss of biodiversity and climate change. Importantly, the report delivers the grim future prediction of more frequent pandemics, which may well be deadlier and more devastating than COVID-19. </p>
<p>It isn’t just more viral pandemics that we might have to face in the future. As our global climate changes, so will the transmission rates of other diseases such as malaria. If malaria begins presenting itself in locations with unprepared healthcare systems, the impacts on healthcare provision could be overwhelming. </p>
<p>Interestingly, there is a way to protect people from malaria – introducing a single faulty gene for the sickle cell anaemia. One copy of this faulty gene gives you <a href="https://www.newscientist.com/article/dn20450-how-sickle-cell-carriers-fend-off%20malaria/#:%7E:text=People%20develop%20sickle%2Dcell%20disease,confers%20some%20resistance%20to%20malaria">a level of protection against malaria</a>. But if two people with a single faulty gene have a baby, the child could develop sickle cell anaemia. This shows just how complicated gene editing can be – you can edit genes to protect a population against one disease, but potentially causing trouble in other ways.</p>
<p>Despite the first hGGe humans already having been born, the reality is that the technique won’t be entering our mainstream lives any time soon. The UK Royal Society <a href="https://royalsociety.org/news/2020/09/heritable-genome-editing-report/">recently stated</a> that heritable genome editing is not ready to be tried in humans safely, although it has urged that if countries do approve hGGe treatment practices, it should focus on specific diseases that are caused by single specific genes, such as sickle cell anaemia and cystic fibrosis. But, as we have seen, it may not make sense to edit out the former in countries with high rates of malaria.</p>
<p>Other major challenges for researchers is unintended genetic modifications at specific sites of the genome which this could lead to a host of further complications to the genome network. The equitable access of treatment provides another sticking point. How would hGGe be regulated and paid for? </p>
<p>The world is not currently ready for hGGe technologies and any progress in this field is likely to occur at a very incremental pace. That being said, this technology will eventually come to feature in humanity for disease prevention. The big question is simply “when?”. Perhaps the answer depends on the severity and frequency of future health crises.</p><img src="https://counter.theconversation.com/content/151313/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Yusef Paolo Rabiah does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>We could start making our genomes equipped to deal with more frequent pandemics. But it may come at a cost.Yusef Paolo Rabiah, PhD Candidate at UCL Science, Technology, Engineering and Public Policy, UCLLicensed 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/1212112019-08-06T12:19:16Z2019-08-06T12:19:16ZGM humans are possible, but do we really want them?<figure><img src="https://images.theconversation.com/files/286263/original/file-20190730-186805-jq2kc8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/1125283274?src=IVEARFWQtSQEl8iFCahYWA-1-0&studio=1&size=huge_jpg">Panuwach/Shutterstock</a></span></figcaption></figure><p>We are entering a new era as a species. For the first time, we are not only able to read our genetic code but also edit it. This will revolutionise our ability to treat disease and it will improve the lives of millions if not billions of people. But it means that, if we want to, we can now edit human embryos to “improve” the characteristics of our children. We will be able to create designer babies and these changes will be passed on to their descendants, which will change the human species forever. </p>
<p>It is worth thinking about the scale of what we can now do. The human genome is made up of 3 billion characters, which is about ten times the size of Encyclopaedia Britannica. This contains all the information needed to make a human, and it determines nearly all our characteristics as individuals (not only height, athletic performance and IQ but also our personality and even political views). We completed the first sequence of the human genome around 20 years ago at a cost of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915252/">US$2.7 billion</a>. We can now sequence a genome for less than the cost of an MRI scan. </p>
<p>In the past decade, there has been an explosion in the technology that allows the genome to be edited. This means that we can change the letters of the genome at nearly any site we choose. This is an incredible feat. It is like being able to walk up to a shelf in a library, select the correct volume, page, line and word and then change only a single character. Amazingly, this can be done in billions of cells at the same time. It is also possible to edit cells inside living animals using viruses to make the genetic changes.</p>
<p>Genome editing will be a huge power for good. It means that we can fix broken genes directly. This will allow debilitating genetic disorders, such as <a href="https://www.nature.com/articles/s41436-018-0409-6">sickle cell disease</a> and <a href="https://www.bbc.co.uk/news/health-45355556">muscular dystrophy</a>, to be cured. We will also be able to use this technology to reprogram cells to kill cancerous cells and perhaps even modify organs to reduce cholesterol levels. This can probably be done with few ethical problems by modifying cells of specific tissues.</p>
<h2>Changing the germline</h2>
<p>By contrast, editing the genome of human embryos is hugely problematic. Editing the embryo when it is a single cell causes genetic changes to occur in every cell in the baby’s body, including their reproductive organs. This means that the changes will not only be made to the baby but all their descendants. </p>
<p>Scientists have found that it is remarkably straightforward to edit mammalian embryos using IVF technology to inject tiny quantities of editing molecules. This has been optimised to generate thousands of genetically modified laboratory animals, which has led to rapid advances in our understanding of many biological processes and disease models. Yet the same technology can be used to edit human embryos, which are very similar to other mammalian embryos. </p>
<p>The main reasons people are likely to edit human embryos is for augmentation, such as improving intelligence or height. It is unlikely to prove that useful for treating genetic disease because nearly all severe genetic disorders can be prevented by pre-implantation genetic diagnosis. Here the embryo is tested to check if it has a mutation before it is put back into the uterus. </p>
<p>The only time pre-implantation diagnosis won’t work is the very rare instance when both parents have the same recessive genetic condition when there is a 100% chance the baby will be affected. But it would still only be justifiable to do germline editing if the disorder is not treatable in another way, such as gene editing of the affected organs.</p>
<h2>Already happening</h2>
<p>In 2018, the Chinese scientist He Jiankui <a href="https://www.nature.com/articles/d41586-018-07545-0">edited human embryos</a> try to make babies resistant to HIV. This led to an outcry in part because it is not possible to ensure the safety of editing human embryos at present and the risks could not be justified because transmission of HIV from mother to baby is very rare with proper medical intervention.</p>
<p>Despite this, Russian scientist <a href="https://institutions.newscientist.com/article/2208777-exclusive-five-couples-lined-up-for-crispr-babies-to-avoid-deafness/">Denis Rebrikov</a> now appears determined to do germline genome editing. This also seems to be a vanity project rather than being in the best interests of the parents or children involved. But it is interesting because it demonstrates how difficult it is to find cases where it is possible to even tenuously justify germline editing; paradoxically helping the argument that it should be outlawed.</p>
<p>Rebrikov has managed to track down five couples where both parents have the same genetic mutation causing deafness. But this mutation does not always cause severe deafness - it can only cause mild hearing loss and this is not predictable in advance. Importantly, severe cases are readily treatable with cochlear implants, which are effective. </p>
<p>The edit needed to fix this defect is not straightforward. He will have to discard at least half of the embryos he tries to edit. And there is a risk he will cause unintended mutations that will not be detectable until after the children are born. </p>
<p>Some people argue that genome editing embryos is ethically justifiable because it means you don’t have to discard embryos, unlike pre-implantation genetic diagnosis. But cells that can create viable humans will always have to be destroyed to test that the edit has been successful. </p>
<p>If we develop technology for editing human embryos, it is likely to lead to widespread human augmentation. Many of the genetic sequences associated with intelligence and athletic performance are already known and recent advances in editing technology mean that it will soon be possible to make hundreds of precise changes at the same time. This raises the possibility that, in the future, parents will be able to choose to have sets of edits to improve IQ, athletic performance and appearance, simultaneously. </p>
<p>If it is taken up by large numbers of people, it is likely people will feel obliged to have their offspring genetically augmented to give them a good chance in life. Unscrupulous governments are also likely to use this technology to generate elite athletes if doping programmes of the past are anything to go by, and it isn’t too difficult to see the potential advantages of genetically engineered soldiers.</p>
<p>It is important that, as a society, we understand the potential ramifications of allowing editing of human embryos and that we do not use this technology indiscriminately.</p><img src="https://counter.theconversation.com/content/121211/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>James Davies is funded by the Medical Research Council and is a Co-founder of Nucleome Therapeutics.</span></em></p>A Russian scientist is preparing to do germline gene editing. Here’s why that’s a problem.James Davies, Clinician Scientist and Consultant Haematologist, University of OxfordLicensed 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/1136392019-03-15T19:44:58Z2019-03-15T19:44:58ZCRISPR gene editing: Why we need Slow Science<figure><img src="https://images.theconversation.com/files/264022/original/file-20190314-28468-1v3lii1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Experts have called for a moratorium on clinical research with CRISPR/Cas9 gene editing
of the germline — that is changing heritable DNA in sperm, eggs or embryos to make genetically modified children. </span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>In a <a href="https://www.nature.com/articles/d41586-019-00726-5">newly published article in <em>Nature</em></a>, a group of prominent scientists and ethicists have called for a moratorium on clinical research using <a href="https://theconversation.com/what-is-crispr-gene-editing-and-how-does-it-work-84591">CRISPR/Cas9 gene editing</a>. </p>
<p>This moratorium deals with the use of CRISPR/Cas9 gene editing of the germline — changing heritable DNA in sperm, eggs or embryos to make genetically modified children. </p>
<p>In other words, this would be a temporary ban on experiments that <a href="https://theconversation.com/why-we-are-not-ready-for-genetically-designed-babies-107756">might result in more “CRISPR babies.”</a></p>
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<a href="https://theconversation.com/opening-pandoras-box-gene-editing-and-its-consequences-108003">Opening Pandora's Box: Gene editing and its consequences</a>
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<p>The document was signed and authored by a number of prominent ethicists and scientists, including CRISPR pioneers <a href="https://www.emmanuelle-charpentier-lab.org/our-team/emmanuelle-charpentier/">Emmanuelle Charpentier</a> (one of the co-discovers of the CRISPR/Cas9) and <a href="https://zlab.bio">Feng Zhang</a> (one of the first to use CRISPR in human cells), as well as <a href="https://www.broadinstitute.org/bios/eric-s-lander">geneticist Eric Lander</a> and bioethicists <a href="https://www.dal.ca/sites/noveltechethics/our-people/francoise-baylis.html">Françoise Baylis</a> and <a href="https://www.otago.ac.nz/bioethics/people/academic/profile/?id=665">Jing-Bao Nie</a>. </p>
<p>However, CRISPR researcher Jennifer Doudna (the other co-discoverer of the CRISPR/Cas9 system) refused to sign this call for a moratorium. She told <a href="https://www.washingtonpost.com/science/2019/03/13/nih-top-scientists-call-moratorium-gene-edited-babies/?noredirect=on&utm_term=.c452381d4f8a"><em>The Washington Post</em></a>: “My feeling is, this is effectively just rehashing what’s been going on for several years.” </p>
<p>This is a contentious point, as the word moratorium has been used sparsely by the scientists involved in this research. Many of the signatories have, however, been vocal about <a href="https://www.broadinstitute.org/bios/david-liu">their views</a> on <a href="https://www.nejm.org/doi/full/10.1056/NEJMp1506446">germline gene editing</a> in the past. </p>
<p>By asking for a global moratorium, the signatories do not mean a permanent ban, but rather, a temporary one — to allow for the development of an international governance framework surrounding <a href="https://www.geneticsandsociety.org/internal-content/about-human-germline-gene-editing">human germline genome editing</a>. Specifically, they suggest a five-year moratorium, a period of time sufficient to allow critical conversations and stakeholder engagement. </p>
<p>Importantly, they are not calling for a unanimous decision among nations either. Countries would be allowed to come up with their own regulatory framework considering the ethical, scientific, technical and medical considerations of CRISPR/Cas9 germline gene editing.</p>
<h2>Slowing down science for the common good</h2>
<p>CRISPR/Cas9 gene editing has moved forward at unprecedented speed since CRISPR was first used in human cells in vitro in 2013 to claims of the birth of the <a href="https://www.sciencenews.org/article/gene-edited-babies-top-science-stories-2018-yir">first germline gene-edited babies in 2018</a>. This is very concerning, especially when the medical need and social risks are still being debated and the safety and efficacy of the treatments are still largely unknown.</p>
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<p>In our view, what the authors of the recent <em>Nature</em> editorial are asking for is Slow CRISPR Science. <a href="http://slow-science.org/">Slow Science</a> — a response to the increasing speed and corporate interest driving the scientific endeavour, and the “publish or perish paradigm” — was built on concepts of the <a href="https://www.slowfood.com/">Slow Food</a> movement. </p>
<p>Slow Food was a direct response to Fast Food, a system in which the environment, people and economies were often jeopardized at the expense of corporate interests that ostensibly provided quick and easy meals. Ideally, the Slow movement is not calling for “less productivity or efficiency” but for more thoughtful and engaging work be done in the food industry and in science.</p>
<p>In terms of gene editing, moving slow would mean perfecting non-heritable gene-editing techniques in patients before attempting ethically charged and technically more difficult heritable gene-editing clinical trials (which appear to be driven by profit or the need to be first, rather than societal need or the common good).</p>
<p>J. Benjamin Hurlbut, an associate professor of biology and society at Arizona State University, wrote in a <a href="https://www.nature.com/articles/d41586-018-07881-1"><em>Nature</em> commentary</a> in early January 2019: </p>
<blockquote>
<p>“To move forward in a positive direction, science must not presume to set the destination for a technology, but should follow the direction that we, the people, provide.”</p>
</blockquote>
<p>Slow CRISPR science would allow for proper consultation with appropriate stakeholders and the public before making the decision to move forward.</p>
<h2>A divided scientific community</h2>
<p>Scientific communities are not in agreement on the issue of a moratorium. In fact, a commentary published in <em>Science</em> in 2015 pushed for “<a href="http://science.sciencemag.org/content/348/6230/36">a prudent path forward</a>” and discussed what steps should be taken to ensure ethical and safe use of this technology. </p>
<p>However, the word <em>moratorium</em> was never used in this document. Further, many of the authors of the 2015 publication have shied away from a moratorium, with much of the organizing committee of the <a href="http://www.nationalacademies.org/hk/">2018 Human Genome Editing Summit</a> (many of whom were also authors on the 2015 <em>Science</em> article) <a href="http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=11282018b">suggesting a “translational pathway”</a> on human germline genome editing. </p>
<p>This is in direct conflict with the language in the concluding statement of the 2015 Human Gene Editing Summit that considered germline genome editing “<a href="https://www.nap.edu/read/21913/chapter/1#6">irresponsible</a>” until relevant safety and efficacy concerns were addressed and “broad societal consensus” was achieved.</p>
<p>Many have effectively skipped to the question of, “How we can do this,” rather than, “Should we do this?” </p>
<p>Ultimately a period of time to pause and reflect would allow for citizens in each nation to have the important conversation of whether their society condones germline genome editing. Each society has to decide for themselves if the rewards outweigh the risks, informed by science but not dictated by it.</p>
<h2>Time to get it right</h2>
<p>For Canada, the moratorium will have little effect on CRISPR research activity as germline gene editing of embryos is already banned under the <a href="https://laws-lois.justice.gc.ca/eng/acts/a-13.4/">2004 Assisted Human Reproduction Act</a>. </p>
<p>Clearly the stakes are high, and missteps in the early applications of CRISPR to human health may result in an all-out ban on this technology, which holds such incredible promise for alleviating human suffering by curing genetic disease. </p>
<p>Therefore, a prudent step in our view is to temporarily press pause on germline gene editing to allow deeper contemplation of the risks and benefits. In essence, this is what these scientists and ethicists are calling for in their proposed moratorium. </p>
<p>They are requesting time to pause and reflect. Time to conduct the appropriate consultations with relevant stakeholders, and (very importantly) the public in an attempt to achieve broad societal consensus. And finally, time to develop the most robust and precise gene-editing tools so that when we use CRISPR/Cas9 to rewrite the source code of humanity, we get it right.</p>
<p><em>This is a corrected version of a story originally published March 15, 2019. The earlier story misattributed a quote calling for “broad scientific consensus” on human germline genome editing. The quote has been removed from the corrected version.</em></p><img src="https://counter.theconversation.com/content/113639/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Landon J Getz receives funding from the Natural Sciences and Engineering Research Council of Canada. </span></em></p><p class="fine-print"><em><span>Graham Dellaire receives funding from the Canadian Institutes of Health Research (CIHR). </span></em></p>CRISPR gene editing should learn from the Slow Food movement. Scientists must allow time for critical conversations and perfecting of techniques before rewriting the source code of humanity.Landon J Getz, Vanier Scholar and Ph.D. Candidate in Microbiology and Immunology, Dalhousie UniversityGraham Dellaire, Director of Research and Professor of Pathology, Dalhousie UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1136272019-03-15T19:19:14Z2019-03-15T19:19:14ZEditing genes shouldn’t be too scary – unless they are the ones that get passed to future generations<figure><img src="https://images.theconversation.com/files/264020/original/file-20190314-28479-o5as8r.jpg?ixlib=rb-1.1.0&rect=0%2C153%2C4268%2C3475&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Gene editing a fertilized human embryo. </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/gene-editing-science-vitro-genetic-crispr-1263162556">Lightspring/Shutterstock.com</a></span></figcaption></figure><p>Gene editing is one of the <a href="https://theconversation.com/how-a-scientist-says-he-made-a-gene-edited-baby-and-what-health-worries-may-ensue-107764">scarier things in the science news</a>, but not all gene editing is the same. It matters whether researchers edit “somatic” cells or “germline” cells. </p>
<p>Germline cells are the ones that propogate into an entire organism – either cells that make sperm and eggs (known as germ cells), or the cells in an early embryo that will later differentiate into different functions. What’s critical about those particular cells is that a change or mutation in one will go on to affect every cell in the body of a baby that grows from them. That’s why scientists are calling for a <a href="http://doi.org/10.1038/d41586-019-00788-5">moratorium on editing the genes of germ cells or germline cells</a>. </p>
<p>Somatic cells are everything else – cells in particular organs or tissues that perform a specific function. Skin cells, liver cells, eye cells and heart cells are all somatic. Changes in somatic cells are much less significant than changes in germline cells. If you get a mutation in a liver cell, you may end up with more mutant liver cells as the mutated cell divides and grows, but it will never affect your kidney or your brain.</p>
<p>Our bodies accumulate mutations in somatic tissues throughout our lives. Most of the time humans never know it or suffer any harm. The exception is when one of those somatic mutations grows out of control leading to cancer.</p>
<p>I am a <a href="http://www.publichealth.pitt.edu/home/directory/eleanor-feingold">geneticist</a> who studies the genetic and environmental causes of a number of different disorders, from birth defects – <a href="https://doi.org/10.1371/journal.pgen.1007501">cleft lip and palate</a> – to diseases of old age like <a href="https://doi.org/10.1038/s41380-018-0246-7">Alzheimer’s</a>. Studying the genome always entails thinking about how the knowledge you generate will be used, and whether those likely uses are ethical. So geneticists have been following the gene editing news with great interest and concern.</p>
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<a href="https://images.theconversation.com/files/264019/original/file-20190314-28512-gztrol.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/264019/original/file-20190314-28512-gztrol.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/264019/original/file-20190314-28512-gztrol.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=360&fit=crop&dpr=1 600w, https://images.theconversation.com/files/264019/original/file-20190314-28512-gztrol.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=360&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/264019/original/file-20190314-28512-gztrol.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=360&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/264019/original/file-20190314-28512-gztrol.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=452&fit=crop&dpr=1 754w, https://images.theconversation.com/files/264019/original/file-20190314-28512-gztrol.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=452&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/264019/original/file-20190314-28512-gztrol.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=452&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">Germ cells are the cells - egg and sperm - that make a baby. Editing genes in these cells will cause permanent changes in the child and all of their progeny.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/structure-human-gametes-ovum-sperm-cell-496197304">arborelza/Shutterstock.com</a></span>
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<p>In gene editing, it matters enormously whether you are messing with a germline cell, and thus an entire future human being and all its future descendants, or just one particular organ. Gene therapy – fixing faulty genes in individual organs – has been one of the <a href="https://onlinelibrary.wiley.com/doi/full/10.1002/jgm.3015">great hopes</a> of medical science for decades. There have been a few successes, but more failures. Gene editing may make gene therapy more effective, potentially curing important diseases in adults. The National Institutes of Health runs a well-respected and highly ethical <a href="https://commonfund.nih.gov/editing">research program</a> to develop tools for safe and effective gene editing to cure disease.</p>
<p>But editing germline cells and creating babies whose genes have been manipulated is a very different story, with multiple ethical issues. The first set of concerns is medical – at this point society doesn’t know anything about the safety. “Fixing” the cells in the liver of someone who might otherwise die of liver disease is one thing, but “fixing” all of the cells in a baby who is otherwise healthy is a much higher-risk proposition. This is why the recent announcement that a Chinese scientist had done just that created such an uproar.</p>
<p>But even if we knew the procedure was safe, gene editing of the germline would still catapult us straight into all of the “designer baby” controversies and the problems of creating a world where people try to micromanage their offspring’s genes. It does not take much imagination to fear that gene editing will could bring us a new era of eugenics and discrimination. </p>
<p>Does gene editing still sound scary? It should. But it makes a big difference whether you are manipulating individual organs or whole human beings.</p><img src="https://counter.theconversation.com/content/113627/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Eleanor Feingold 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 worldwide are calling for a moratorium on gene editing in germline cells. But what is a germline cell? How does it differ from other cells in our body? Why does it matter if we edit them?Eleanor Feingold, Professor, Departments of Human Genetics and Biostatistics, University of PittsburghLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/817972017-08-01T22:36:56Z2017-08-01T22:36:56ZHuman genome editing: We should all have a say<figure><img src="https://images.theconversation.com/files/180420/original/file-20170731-22134-1s9uda.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Controversial gene editing should not proceed without citizen input and societal consensus.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>Shoukhrat Mitalipov, a reproductive biologist at Oregon Health and Science University, is nothing if not a pioneer. In 2007, his team published proof-of-principle research in primates showing it was possible to <a href="https://dx.doi.org/10.1038/nature06357">derive stem cells from cloned primate embryos</a>. In 2013, his team was the first to <a href="https://theconversation.com/human-embryonic-stem-cells-grown-from-skin-tissue-14339">create human embryonic stem cells by cloning</a>. Now, in 2017, <a href="https://dx.doi.org/10.1038/nature23305">his team has reported safely and effectively modifying human embryos with the MYBPC3 mutation (which causes myocardial disease)</a> using the gene editing technique <a href="https://theconversation.com/explainer-crispr-technology-brings-precise-genetic-editing-and-raises-ethical-questions-39219">CRISPR</a>. </p>
<p>Mitalipov’s team is not the first to genetically modify human embryos. This was first accomplished in 2015 by <a href="http://www.nature.com/news/chinese-scientists-genetically-modify-human-embryos-1.17378">a group of Chinese scientists led by Junjiu Huang</a>. Mitalipov’s team, however, may be the first to demonstrate basic safety and efficacy using the CRISPR technique. </p>
<p>This has serious implications for the ethics debate on human germline modification which involves inserting, deleting or replacing the DNA of human sperm, eggs or embryos to change the genes of future children. </p>
<h2>Ethically controversial</h2>
<p>Those who support human embryo research will argue that Mitalipov’s research to alter human embryos is ethically acceptable because the embryos were not allowed to develop beyond 14 days (the widely accepted international limit on human embryo research) and because the modified embryos were not used to initiate a pregnancy. They will also point to the future potential benefit of correcting defective genes that cause inherited disease. </p>
<p>This research is ethically controversial, however, because it is a clear step on the path to making heritable modifications - genetic changes that can be passed down through subsequent generations.</p>
<h2>Beyond safety and efficacy</h2>
<p>Internationally, <a href="http://en.unesco.org/news/unesco-panel-experts-calls-ban-editing-human-dna-avoid-unethical-tampering-hereditary-traits">UNESCO has called for a ban</a> on human germline gene editing. And the “Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine” – the <a href="http://www.coe.int/en/web/conventions/full-list/-/conventions/rms/090000168007cf98">Oviedo Convention</a> – specifies that “an intervention seeking to modify the human genome may only be undertaken for preventive, diagnostic or therapeutic purposes and only if its aim is not to introduce any modification in the genome of any descendants.”</p>
<p>In a move away from the positions taken by UNESCO and included in the Oviedo Convention, in 2015 the 12-person Organizing Committee of the first <a href="http://nationalacademies.org/gene-editing/Gene-Edit-Summit/">International Summit on Human Gene Editing</a> (of which I was a member) <a href="http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=12032015a">issued a statement</a> endorsing basic and preclinical gene editing research involving human embryos. </p>
<p>The statement further stipulated, however, that: “It would be irresponsible to proceed with any clinical use of germline editing unless and until (i) the relevant safety and efficacy issues have been resolved, based on appropriate understanding and balancing of risks, potential benefits, and alternatives, and (ii) there is broad societal consensus about the appropriateness of the proposed application.”</p>
<p>Mitalipov’s research aims to address the first condition about safety and efficacy. But what of the second condition which effectively recognizes that the human genome belongs to all of us and that it is not for scientists or other elites to decree what should or should not happen to it?</p>
<h2>Modification endorsed</h2>
<p>Since the 2015 statement was issued, many individuals and groups have tried to set aside the recommendation calling for a broad societal consensus. </p>
<p>For example, in February 2017, the U.S. National Academy of Sciences and National Academy of Medicine <a href="https://www.nap.edu/catalog/24623/human-genome-editing-science-ethics-and-governance">published a report</a> endorsing germline modification. It states unequivocally that “clinical trials using heritable germline genome editing should be permitted” provided the research is only for compelling reasons and under strict oversight limiting uses of the technology to specified criteria.</p>
<h2>Seeds of change in Canada</h2>
<p>In Canada, it is illegal to modify human germ cells. Altering “the genome of a cell of a human being or in vitro embryo such that the alteration is capable of being transmitted to descendants” is among the activities prohibited in the 2004 <a href="http://laws-lois.justice.gc.ca/eng/acts/a-13.4/FullText.html">Assisted Human Reproduction Act</a>. </p>
<p>Worried that “Canadian researchers may fall behind on the international scene” and that “restrictive research policies may lead to medical tourism,” the Canadian Institutes for Health Research (with input from the <a href="http://stemcellnetwork.ca/about-scn/">Canadian Stem Cell Network</a>) has begun to plant the seeds of change. </p>
<p>In its <a href="http://www.cihr-irsc.gc.ca/e/50158.html">Human Germline Gene Editing</a> report, CIHR hints at the benefits of changing the legislation. It also suggests professional self-regulation and research funding guidelines could replace the current federal statutory prohibition.</p>
<h2>Future of the species</h2>
<p>With Mitalipov’s technological advances and increasing suggestions from researchers that heritable modifications to human embryos be permitted, it is essential that citizens be given opportunities to think through the ethical issues and to work towards broad societal consensus. </p>
<p>We are talking about nothing less than the future of the human species. No decisions about the modification of the germline should be made without broad societal consultation. </p>
<p>Nothing about us without us!</p><img src="https://counter.theconversation.com/content/81797/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Françoise Baylis has received past funding from the Canadian Institutes for Health Research and the Stem Cell Network.</span></em></p>A team in the U.S. is said to have safely and effectively altered human embryos. The news is a reminder that citizens must be consulted on developments potentially affecting the future of the species.Françoise Baylis, Research Professor, Philosophy, Dalhousie UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/817322017-07-28T15:40:07Z2017-07-28T15:40:07ZEditing human embryos with CRISPR is moving ahead – now’s the time to work out the ethics<figure><img src="https://images.theconversation.com/files/180229/original/file-20170728-15340-1460v93.jpg?ixlib=rb-1.1.0&rect=35%2C73%2C1173%2C805&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">There's still a way to go from editing single-cell embryos to a full-term 'designer baby.'</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/zeissmicro/27771482282">ZEISS Microscopy</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>The announcement by researchers in Portland, Oregon that they’ve successfully modified the genetic material <a href="https://www.technologyreview.com/s/608350/first-human-embryos-edited-in-us/">of a human embryo</a> took some people by surprise.</p>
<p>With headlines referring to “<a href="https://www.businesslive.co.za/bd/world/americas/2017-07-27-us-university-edits-embryo-genes-in-experiment-hailed-as-groundbreaking/">groundbreaking</a>” research and “<a href="http://www.dailymail.co.uk/sciencetech/article-4734364/First-editing-human-embryos-carried-United-States.html">designer babies</a>,” you might wonder what the scientists actually accomplished. This was a big step forward, but hardly unexpected. As this kind of work proceeds, it continues to raise questions about ethical issues and how we should we react.</p>
<h2>What did researchers actually do?</h2>
<p>For a number of years now we have had the ability to alter genetic material in a cell, using a technique called CRISPR.</p>
<p>The DNA that makes up our genome comprises long sequences of base pairs, each base indicated by one of four letters. These letters form a genetic alphabet, and the “words” or “sentences” created from a particular order of letters are the genes that determine our characteristics.</p>
<p>Sometimes words can be “misspelled” or sentences slightly garbled, resulting in a disease or disorder. Genetic engineering is designed to correct those mistakes. CRISPR is a tool that enables scientists to target a specific area of a gene, working like the search-and-replace function in Microsoft Word, to remove a section and insert the “correct” sequence. </p>
<p>In the last decade, CRISPR has been the primary tool for those seeking to modify genes – human and otherwise. Among other things, it has been used in experiments to make <a href="https://doi.org/10.1038/nbt.3439">mosquitoes resistant to malaria</a>, genetically <a href="http://www.genengnews.com/gen-exclusives/crispr-applications-in-plants/77900846">modify plants to be resistant to disease</a>, explore the possibility of <a href="https://doi.org/10.1038/nature.2015.18448">engineered pets</a> and <a href="https://www.sciencenews.org/blog/science-ticker/crispr-used-cows-help-fight-tuberculosis">livestock</a>, and potentially treat some human diseases (including <a href="http://sites.tufts.edu/crispr/applications/hiv-treatment/">HIV</a>, <a href="https://doi.org/10.15252/emmm.201606325">hemophilia</a> and <a href="https://doi.org/10.1016/j.omtn.2016.12.012">leukemia</a>).</p>
<p>Up until recently, the focus in humans has been on changing the cells of a single individual, and not changing eggs, sperm and early embryos – what are called the “germline” cells that pass traits along to offspring. The theory is that focusing on non-germline cells would limit any unexpected long-term impact of genetic changes on descendants. At the same time, this limitation means that we would have to use the technique in every generation, which affects its potential therapeutic benefit.</p>
<p>Earlier this year, an international committee convened by the National Academy of Sciences <a href="https://doi.org/10.17226/24623">issued a report</a> that, while highlighting the concerns with human germline genetic engineering, laid out a series of <a href="http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=24623">safeguards and recommended oversight</a>. The report was widely regarded as opening the door to embryo-editing research.</p>
<p>That is exactly what happened in Oregon. Although this is the first study reported in the United States, similar research has been <a href="https://doi.org/10.1007/s13238-015-0153-5">conducted in China</a>. This new study, however, apparently avoided previous errors we’ve seen with CRISPR – such as changes in other, untargeted parts of the genome, or the desired change not occurring in all cells. Both of these problems had made scientists wary of using CRISPR to make changes in embryos that might eventually be used in a human pregnancy. Evidence of more successful (and thus safer) CRISPR use may lead to additional studies involving human embryos.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/180203/original/file-20170728-5295-1tgc36j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/180203/original/file-20170728-5295-1tgc36j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/180203/original/file-20170728-5295-1tgc36j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=402&fit=crop&dpr=1 600w, https://images.theconversation.com/files/180203/original/file-20170728-5295-1tgc36j.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=402&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/180203/original/file-20170728-5295-1tgc36j.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=402&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/180203/original/file-20170728-5295-1tgc36j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=505&fit=crop&dpr=1 754w, https://images.theconversation.com/files/180203/original/file-20170728-5295-1tgc36j.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=505&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/180203/original/file-20170728-5295-1tgc36j.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=505&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">We have a ways to go before ordering up desired traits in a future baby. Researchers at Oregon Health and Science University say they worked with single-cell embryos, inserting CRISPR chemicals at the time of fertilization.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/lunarcaustic/3233482244">lunar caustic</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>What didn’t happen in Oregon?</h2>
<p>First, this study did not entail the creation of “designer babies,” despite some news headlines. The research involved only early stage embryos, outside the womb, none of which was allowed to develop beyond a few days.</p>
<p>In fact, there are a number of existing limits – both policy-based and scientific – that will create barriers to implanting an edited embryo to achieve the birth of a child. There is a <a href="https://www.nih.gov/about-nih/who-we-are/nih-director/statements/statement-nih-funding-research-using-gene-editing-technologies-human-embryos">federal ban on funding</a> gene editing research in embryos; in some states, there are also <a href="https://nyscf.org/scmapus">total bans on embryo research</a>, regardless of how funded. In addition, the implantation of an edited human embryos would be regulated under the <a href="https://humansubjects.nih.gov/pregnant-women-human-fetuses-neonates">federal human research regulations</a>, the <a href="https://www.fda.gov/biologicsbloodvaccines/cellulargenetherapyproducts/">Food, Drug and Cosmetic Act</a> and potentially the federal rules regarding <a href="https://wwwn.cdc.gov/CLIA/Regulatory/default.aspx">clinical laboratory testing</a>.</p>
<p>Beyond the regulatory barriers, we are a long way from having the scientific knowledge necessary to design our children. While the Oregon experiment focused on a single gene correction to inherited diseases, there are few human traits that are controlled by one gene. Anything that involves multiple genes or a gene/environment interaction will be less amenable to this type of engineering. Most characteristics we might be interested in designing – such as intelligence, personality, athletic or artistic or musical ability – are much more complex.</p>
<p>Second, while this is a significant step forward in the science regarding the use of the CRISPR technique, it is only one step. There is a long way to go between this and a cure for various disease and disorders. This is not to say that there aren’t concerns. But we have some time to consider the issues before the use of the technique becomes a mainstream medical practice.</p>
<h2>So what should we be concerned about?</h2>
<p>Taking into account the cautions above, we do need to decide when and how we should use this technique.</p>
<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. Even in this country it can be difficult to craft guidelines that restrict only the research someone finds objectionable, while allowing other important research to continue. Additionally, the use of assisted reproductive technologies (IVF, for example) is <a href="http://www.rockinst.org/pdf/health_care/2009-07-States_Regulation_ART.pdf">largely unregulated in the U.S.</a>, and the decision to put in place restrictions will certainly raise objections from both potential parents and IVF providers.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/180211/original/file-20170728-18243-1g5vqx3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/180211/original/file-20170728-18243-1g5vqx3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/180211/original/file-20170728-18243-1g5vqx3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/180211/original/file-20170728-18243-1g5vqx3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/180211/original/file-20170728-18243-1g5vqx3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/180211/original/file-20170728-18243-1g5vqx3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/180211/original/file-20170728-18243-1g5vqx3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/180211/original/file-20170728-18243-1g5vqx3.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">Who should be able to use this technology? And who should decide?</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/j2dread/5595599661">Johnathan D. Anderson</a>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>Moreover, there are important questions about cost and access. Right now most assisted reproductive technologies are available only to higher-income individuals. A handful of <a href="http://www.ncsl.org/research/health/insurance-coverage-for-infertility-laws.aspx">states mandate infertility treatment coverage</a>, but it is very limited. How should we regulate access to embryo editing for serious diseases? We are in the midst of a <a href="https://theconversation.com/us/topics/us-health-care-reform-40185">widespread debate</a> about health care, access and cost. If it becomes established and safe, should this technique be part of a basic package of health care services when used to help create a child who does not suffer from a specific genetic problem? What about editing for nonhealth issues or less serious problems – are there fairness concerns if only people with sufficient wealth can access?</p>
<p>So far the promise of genetic engineering for disease eradication has not lived up to its hype. Nor have many other milestones, like the 1996 <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 of Dolly the sheep</a>, resulted in the feared apocalypse. The announcement of the Oregon study is only the next step in a long line of research. Nonetheless, it is sure to bring many of the issues about embryos, stem cell research, genetic engineering and reproductive technologies back into the spotlight. Now is the time to figure out how we want to see this gene-editing path unfold.</p><img src="https://counter.theconversation.com/content/81732/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jessica Berg 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 news may have come as a surprise, but it probably shouldn’t have. A bioethics expert walks through how big a deal this announcement is – and what we should be considering now.Jessica Berg, Law Dean; Professor of Law; and Professor of Bioethics & Public Health, Case Western Reserve UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/669182016-10-24T06:41:20Z2016-10-24T06:41:20ZCRISPR gene-editing controversy shows old ideas about East and West still prevail<figure><img src="https://images.theconversation.com/files/142827/original/image-20161024-15941-xkgcfv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">CRISPR uses segments of bacterial DNA that can make targeted cuts in a genome when paired with a specific guide protein.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/kyz/3340435836/">Stuart Caie/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>The debate that followed initial experiments using the <a href="https://www.nap.edu/catalog/23405/gene-drives-on-the-horizon-advancing-science-navigating-uncertainty-and">CRISPR-Cas9</a> genome editing tool show that old stereotypes about Asia still resonate in the West. </p>
<p>CRISPR-Cas9 is a gene editing tool that was <a href="http://science.sciencemag.org.libproxy1.nus.edu.sg/content/sci/337/6096/816.full.pdf">first demonstrated</a> in US and Swedish labs in 2012. Basically, it uses segments of bacterial DNA that can make targeted cuts in a genome when paired with a specific guide protein (in this case, Cas9). </p>
<p>The technique is relatively uncomplicated compared with previous genome editing tools, which have been studied by scientists for more than 50 years. If applied to the genome of human germline cells, which pass on genetic material to produce human embryos, CRISPR-Cas9 has – at least in theory – the capability to <a href="http://www.nytimes.com/2015/11/15/magazine/the-crispr-quandary.html?_r=0">alter humanity</a> as we understand it. </p>
<p>Once certain genes are introduced or removed in germline cells (also known as gametes), the changes are passed onto the next generation. Given its potential to be misapplied towards eugenic ends and related ethical concerns, <a href="http://www.nature.com/news/don-t-edit-the-human-germ-line-1.17111">scientists generally agree</a> that genetic modification of human gametes and embryos should not be done for reproductive purposes. </p>
<p>But it was less clear if genome editing in a human embryo that could not be used for reproduction was ethically acceptable. </p>
<h2>Confecting controversy</h2>
<p>In the spring of 2015, Junjiu Huang and his research team at Sun Yat-sen University in Guangzhou, China, used CRISPR-Cas9 to edit the genome of <em>non-viable</em> human embryos. The <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417674/">publication of that study</a> generated <a href="http://www.nytimes.com/2015/06/30/science/a-scientific-ethical-divide-between-china-and-west.html">a huge amount of controversy</a>, with an article in the New York Times claiming:</p>
<blockquote>
<p>medical researchers in China are stepping over ethical boundaries long accepted in the West.</p>
</blockquote>
<p>But such research could have also been possible in some Western countries, such as in the UK.</p>
<p>A recurring theme in such controversies is the concern that responsible conduct leads to loss of <a href="http://www.bbc.com/future/story/20160804-china-may-be-the-future-of-genetic-enhancement">competitive advantage</a>, when the same rules do not apply to everyone. </p>
<p>It’s often assumed that countries in Asia have an advantage in moving ahead rapidly with gene editing, stem cell research, cloning and other biotech fields because they don’t share the same religious or political views about the human embryo that prevail in Western countries.</p>
<p>This concern reached a high point for stem cell research when former <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744932/">US president George W Bush introduced a ban</a> on federal funding for research involving newly created human embryonic stem cell lines. </p>
<p><a href="https://papyrus.bib.umontreal.ca/xmlui/bitstream/handle/1866/724/Isasi-Knoppers%20Mind%20the%20Gap_Policy%20Approaches%20to%20Embryonic.pdf;jsessionid=6013B7BCAF7C73ECC794B0EB089BFCF0?sequence=1">Countries such as Germany and Italy</a> also impose legal restrictions on research involving the human embryo. In Germany, memory of <a href="https://theconversation.com/is-it-ethical-to-use-data-from-nazi-medical-experiments-39928">inhumane medical experiments</a> carried out by the Nazi regime has led to a comprehensibly more conservative stance towards technologies that could be misapplied toward eugenic ends. </p>
<p>And Italy is opposed to such research due mainly to the religious belief that a human embryo should be treated as morally equivalent to a person. It’s less clear whether non-viable embryos, such as those used by Huang, would enjoy a similar moral status. </p>
<p>In contrast – and by implication – the research culture in non-Western countries is portrayed as a free-for-all. But such an appraisal is clearly misleading. </p>
<p>For a start, this view assumes that there is a substantial difference in standards between Western countries and their non-Western competitors. The Chinese research team were perceived to have succeeded in their scientific endeavour primarily because China was assumed to have little or no regulatory control over human embryo research.</p>
<p>It also adopts a blinkered view of the competitive landscape: scientific progress depends on far more than differences in the ethical and regulatory environments. <a href="https://www.ncbi.nlm.nih.gov/books/NBK26378/">Many other factors apply</a>, ranging from social and economic systems, the availability of funding and institutional arrangements, and research networks and skills.</p>
<p>Finally, it fails to critically assess the limitations of its own reductionist perception. In his classic work Orientalism, <a href="http://www.postcolonialweb.org/poldiscourse/pol11.html">Edward Said explained</a> how the West had created a dichotomy between the Orient, as irrational, backward and culturally unsophisticated, and itself, as rational, advanced and culturally refined. </p>
<p>Said noted that this kind of blindness was just as much a part of the insights into how the “other” is understood, as it is of and in relation to the “self”. </p>
<h2>Shared ethical standards</h2>
<p>Contrary to what <a href="http://qz.com/441423/why-china-wont-listen-to-western-scientists-about-genetically-modifying-the-human-embryo/">some initial media reports</a> suggested, Huang’s study did not violate generally accepted international guidelines or even the regulatory requirements of scientifically advanced countries. </p>
<p><a href="http://legal.un.org/docs/?symbol=A/RES/59/280">International law</a> does not prohibit research on human embryos, although there’s a <a href="http://www.isscr.org/docs/default-source/guidelines/isscr-guidelines-for-stem-cell-research-and-clinical-translation.pdf?sfvrsn=2">general consensus</a> that all such research should be limited to within 14 days of embryonic development. The embryos are then to be destroyed.</p>
<p>Critically, only non-viable embryos (known technically as dispermic <a href="http://phenomena.nationalgeographic.com/2015/04/22/editing-human-embryos-so-this-happened/">tripronuclear zygotes</a>) were used in Huang’s research. These are embryos that would not be biologically capable of developing into an organism that looks anything like a human foetus. </p>
<p>For the purposes of the study, it was only necessary for the embryos to develop for about 48 hours (or to an eight-cell stage), before they were analysed to better understand the efficacy of the gene-editing technique under investigation.</p>
<p>Human embryo research is subject to <a href="https://www.ncbi.nlm.nih.gov/pubmed/26791577">ethical and regulatory controls in China</a>, just as it is in Western countries. Indeed, apart from some procedural or workflow differences, the requirements that these controls give effect to don’t differ significantly from the requirements in international guidelines and in the regulatory provisions of countries that allow the research. </p>
<p>Chinese regulations impose informed consent and ethics review requirements, for instance, as well as prohibit the application of such research for any reproductive purposes. These are no different from regulatory requirements that apply in many Western European and North American countries.</p>
<h2>The nature of competition</h2>
<p>The relationships between science and its broader social or political environment is a complex one. It should not be surprising to find that the <a href="https://hbr.org/1990/03/the-competitive-advantage-of-nations">nature of competition differs significantly</a> from one country to another. </p>
<p>Competition could be directed towards identifying problems that relate to the health and well-being of people, or it could be aimed at providing accurate and compelling information to promote better choices. In other words, <a href="http://www.nature.com/nmeth/journal/v11/n7/full/nmeth.3026.html">competition could also lead to collaboration</a>.</p>
<p>Where regimes of research governance are concerned, an even broader spectrum of approaches can exist. It is not especially insightful to speculate on scientific progress on the basis of one narrowly construed indicator which, in the context of this debate, is the stringency of ethical or regulatory control in the East versus the West.</p>
<p>Thankfully, baseless assumptions gave way to fair-minded engagement. In December 2015, the US National Academy of Sciences, US National Academy of Medicine, Chinese Academy of Sciences and the UK Royal Society organised an <a href="http://www.nationalacademies.org/gene-editing/Gene-Edit-Summit/index.htm">International Summit</a> in Washington DC on the scientific developments in human gene editing, and related ethical and governance issues. </p>
<p>A <a href="https://www.nap.edu/read/21913/chapter/1#6">statement released</a> from the meeting proposes that gene editing of human eggs, sperms and embryos should be allowed, but only as research in the laboratory. Just as Huang’s research had done.</p>
<p>Gene editing tools, when better understood, could help prevent life-threatening and seriously debilitating conditions, and could help treat currently incurable conditions. Still, for the time being, gene editing is not to be applied in the clinic. </p>
<p>Since this meeting, <a href="http://www.nature.com/news/uk-scientists-gain-licence-to-edit-genes-in-human-embryos-1.19270">scientists in the UK</a> have successfully obtained regulatory approval to use CRISPR-Cas9 in healthy human embryos in order to better understand early embryo development. These genome-edited embryos will only be studied for up to seven days of development, after which they will be destroyed.</p>
<h2>Excesses of Orientalism</h2>
<p>There was rampant speculation in the media less than two decades ago that Western countries would lose out to their non-Western competitors in developing <a href="http://www.stemcellfoundation.net.au/docs/fact-sheets/fact-sheet-4---therapeutic-cloning-(somatic-cell-nuclear-transfer).pdf?sfvrsn=5">therapeutic cloning</a>, a cornerstone technology in <a href="https://www.ncbi.nlm.nih.gov/pubmed/23809322">regenerative medicine</a>. </p>
<p>Ironically, it was in Japan that a new scientific method (known as <a href="http://www.the-scientist.com/?articles.view/articleNo/32765/title/Cell-Re-Programmers-Take-the-Nobel/">induced pluripotent stem cell</a> technique) was developed to allow cloning without destroying a human embryo.</p>
<p>For a time, both after cloning and Huang’s CRISPR experiment, various Western media depicted non-Western societies in ways that were static and crude. This process of “othering” Asia, broadly referred to as <a href="http://www.newworldencyclopedia.org/entry/Orientalism">Orientalism</a>, is problematic for its reductionism and stereotyping. </p>
<p>Sadly, its excesses seem impossible to edit out of human history.</p><img src="https://counter.theconversation.com/content/66918/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Calvin Wai-Loon Ho receives funding from the Singapore government.</span></em></p>Controversy over a Chinese study that used CRISPR-Cas9 gene-editing technology shows how the West still looks at the East through the lens of Orientalism.Calvin Wai-Loon Ho, Assistant Professor of Bioethics, National University of SingaporeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/523262015-12-16T15:52:23Z2015-12-16T15:52:23ZHow close are we to successfully editing genes in human embryos?<figure><img src="https://images.theconversation.com/files/106025/original/image-20151215-23205-32o10z.jpg?ixlib=rb-1.1.0&rect=0%2C31%2C639%2C432&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Eight cells in an embryo at three days.</span> <span class="attribution"><a class="source" href="https://en.wikipedia.org/wiki/Human_embryogenesis#/media/File:Embryo,_8_cells.jpg">ekem, Courtesy: RWJMS IVF Program/wikimedia</a></span></figcaption></figure><p>An important international summit on human gene editing <a href="http://www.theguardian.com/science/2015/dec/03/gene-editing-summit-rules-out-ban-on-embryos-destined-to-become-people-dna-human">recently recommended</a> that researchers go ahead with gene editing human embryos, but keep revisiting how and when such modifications would be appropriate in the clinic. The decision came after some scientists <a href="http://www.nytimes.com/2015/12/04/science/crispr-cas9-human-genome-editing-moratorium.html?_r=0">called for a moratorium</a> on such research.</p>
<p>The recommendation was always going <a href="https://www.washingtonpost.com/opinions/the-great-potential--and-great-risks--of-gene-editing/2015/12/11/ea1607a4-9a09-11e5-8917-653b65c809eb_story.html">to be controversial</a>, with many people concerned that the technology, which could be used to prevent parents from passing on genetic diseases to their children, will be misused and lead to permanent changes in the human gene pool.</p>
<p>But how close are we – is there really reason to be concerned at this point?</p>
<h2>Laboratory promise</h2>
<p>Gene editing of the human germline – those cells that form the sperm and eggs and, from a fertilised egg, will generate every cell in the human body – is different from other types of genetic editing because changes in those cells will be inherited by future generations, to become a permanent change in the human make-up.</p>
<p>Working on human germline cells at the very earliest stages of the formation of an embryo, just after an egg has been fertilised and then implants itself in the womb, is of course impossible to do in a pregnant woman. In <a href="http://www.gurdon.cam.ac.uk/research/surani">my lab</a>, where our focus is on early development, we approach this research using mice and, more recently, by simply growing human cells in a culture dish. In this way we have managed to identify some of the earliest genetic events that “specify” a stem cell to become a germline cell.</p>
<p>At the same time the technology underpinning gene editing, such as the <a href="https://theconversation.com/explainer-crispr-technology-brings-precise-genetic-editing-and-raises-ethical-questions-39219">CRISPR/Cas9</a> – a fast, easy and unprecedentedly precise method for targeting edits to specific genes – is becoming widespread across science. Together with the new ways of studying germline cells in the lab, this is offering a real chance for scientists and the public to consider whether or not editing of the human germline has merit – before any harm can be done.</p>
<p>We can now <a href="http://dev.biologists.org/content/141/2/245">create human “primordial germ cells”</a>, the precursors to eggs and sperm, from embryonic stem cells. It is a delicate and time-consuming procedure, and the resulting cells do not survive beyond the very early stages of development – partly because we have yet to reproduce the conditions that they are designed to thrive in. What we have been able to show is that some of the earliest steps in the development of human primordial germ cells are [different from those in mice](http://www.cell.com/cell/fulltext/S0092-8674(14). This is important as most of the previous results in this area have come from mouse models, indicating that such information cannot actually be wholly extrapolated to describe humans. </p>
<p>Last year, we also managed to generate primordial <a href="http://www.nature.com/news/rudimentary-egg-and-sperm-cells-made-from-stem-cells-1.16636">germ cells from adult body cells</a>, such as human skin cells. We take body cells that have been programmed to revert back into stem cells, and add chemical factors to “re-specify” them as primordial germ cells.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/106046/original/image-20151215-23172-145nf55.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/106046/original/image-20151215-23172-145nf55.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=593&fit=crop&dpr=1 600w, https://images.theconversation.com/files/106046/original/image-20151215-23172-145nf55.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=593&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/106046/original/image-20151215-23172-145nf55.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=593&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/106046/original/image-20151215-23172-145nf55.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=745&fit=crop&dpr=1 754w, https://images.theconversation.com/files/106046/original/image-20151215-23172-145nf55.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=745&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/106046/original/image-20151215-23172-145nf55.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=745&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">It is possible to create gene-edited sperm in mice. But humans may be a different story.</span>
<span class="attribution"><a class="source" href="https://simple.wikipedia.org/wiki/Semen#/media/File:Sperm-20051108.jpg">Gilberto Santa Rosa from Rio de Janeiro, Brazil/wikimedia</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>While these cells don’t survive long either, experiments have shown that introducing such cells into the testes and ovaries of in mice does allow them to continue their development and maturation into sperm and eggs. Remarkably, such mice were able to <a href="https://www.sciencemag.org/content/338/6109/971.full">give birth to healthy offspring</a> raising the prospect of reprogrammed skin cells creating living human beings. For that reason it certainly makes sense to carry out similar studies using primates. Further research might also make it possible to develop working sperm and egg cells entirely in a culture dish. </p>
<h2>Finished blueprint?</h2>
<p>Looking ahead, it is clear that there already is a potential template for editing the human germline. Genome-sequencing methods could also provide for additional checks to ensure that no inadvertent mutations or “off-target” effects have occurred during the editing procedures. </p>
<p>What’s more, if viable sperm and eggs could be grown in the lab from primordial germ cells, they could be used to generate fertilised embryos. Such “pre-implantation” embryos could also be further screened (as is routine now in the in-vitro fertilisation procedure) to ensure transfer to the womb of only those embryos that are free from specific mutations. </p>
<p>So how could this work in a clinic? Imagine combining the procedures in one patient, for example a woman with a disease-causing mutation who does not wish to pass this mutation to her child. Starting with a cell taken from her skin, this is reprogrammed to a primordial germ cell, in which the DNA is then edited to remove the mutated gene. The primordial germ cell is developed into an egg and used to create an embryo for IVF, to be screened and transplanted back into her womb. The child and its subsequent descendants would be free of the mutated gene.</p>
<p>There’s a reason why the summit carefully considered such massive implications and nevertheless recommended to pursue such research. Without making further gains in our knowledge about the fundamental processes in early germ cell and embryo development – starting with growing germ cells for longer in the culture dish – we will not know what we can and cannot safely achieve with the new gene-editing technologies. We are still some way from being able to contribute the necessary biological evidence to society’s debate about which, if any, of these technologies to pursue.</p><img src="https://counter.theconversation.com/content/52326/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Azim Surani receives funding from The Wellcome Trust and Cancer Research UK</span></em></p>We’re not quite there yet but there is already a potential blueprint for editing the human germline.Azim Surani, Director of Germline and Epigenomics Research at the Gurdon Institute, University of CambridgeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/518432015-12-07T10:46:38Z2015-12-07T10:46:38ZWhy treat gene editing differently in two types of human cells?<figure><img src="https://images.theconversation.com/files/104520/original/image-20151206-29716-m84d6a.jpg?ixlib=rb-1.1.0&rect=0%2C1016%2C6116%2C4101&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A snip here, but not a snip there?</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-303373844/stock-photo-gene-editing-health-care-concept-as-molecular-scissors-cutting-a-dna-strand-as-a-medical-science.html">DNA image via www.shutterstock.com</a></span></figcaption></figure><p>At the conclusion of the recent <a href="http://www.nationalacademies.org/gene-editing/Gene-Edit-Summit/index.htm">International Summit on Human Gene Editing</a> in Washington, DC, its organizing committee released a <a href="http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=12032015a">much-anticipated statement</a> recommending how human genetic engineering should be regulated. Co-organized by US, UK and Chinese national academies, the summit gathered preeminent researchers, clinicians and ethicists to grapple with how new gene editing technologies – particularly the method known as CRISPR – should be used. As CRISPR-cas9 is refined in the lab, several <a href="http://www.wired.co.uk/news/archive/2015-04/23/gene-editing-human-embryos-first-controversial-study">actual</a> and <a href="http://www.theguardian.com/science/2015/sep/18/uk-scientists-seek-permission-to-genetically-modify-human-embryos?CMP=share_btn_tw">proposed</a> trials using the technique have raised ethical concerns. </p>
<p>Somewhat surprisingly, the summit statement was generally supportive of human gene editing. It suggested that research into genetic modifications should continue as long as it doesn’t lead to a pregnancy. The statement opposed (for now) clinical use of <a href="http://ghr.nlm.nih.gov/glossary=germline">germline</a> modifications – those are genetic changes that would be in every cell of a resulting baby and be passed on to future generations. The committee, though, approved of clinical use of <a href="http://ghr.nlm.nih.gov/glossary=somaticcell">somatic</a> (body) cell gene therapies that affect only the treated individual, not future offspring.</p>
<p>There is not yet consensus within the gene editing community over what the ethical and legal limits to techniques like CRISPR should be. The statement contributes a reasonably clear position: research into using gene editing to cure diseases should continue. But by saying we should hold off on non-research changes to genes in sperm, eggs and embryos, I’d suggest the ethical distinction they make between modifying body cells and germline cells is tenuous. This leads to inconsistent regulatory standards that risk either underregulating somatic therapies or overregulating germline therapies.</p>
<h2>Both yes and no</h2>
<p>The committee’s position is at once liberal and conservative.</p>
<p>On the one hand, it promotes more research into germline editing, and does not suggest forever shutting the door on reproductive applications – policies are to be revisited regularly. <a href="http://www.nature.com/news/don-t-edit-the-human-germ-line-1.17111">Others</a> had <a href="https://www.washingtonpost.com/news/innovations/wp/2015/09/08/why-theres-an-urgent-need-for-a-moratorium-on-gene-editing/">called</a> for a <a href="https://theconversation.com/crispr-cas-gene-editing-technique-holds-great-promise-but-research-moratorium-makes-sense-pending-further-study-43371">stronger moratorium</a> or even a ban on such research. These voices are <a href="http://www.ipscell.com/2015/12/perspectives-no-moratorium-from-organizers-of-geneeditsummit/">concerned</a> that medical risks and ethical pitfalls have not been adequately taken into account. </p>
<p>But the committee’s position is also conservative, as it does not imply a major change to gene-editing “business as usual” in the host countries. Existing <a href="http://www.businessinsider.sg/china-edited-human-genome-laws-2015-4/#.VmJ29Y9OKM8">Chinese guidelines</a> and <a href="http://www.lawandreligionuk.com/2015/09/08/genome-editing-of-human-cells/">UK law</a> are already in line with this new statement. They ban reproductive germline modifications. But non-reproductive germline research and clinical somatic therapy are permitted under certain conditions. </p>
<p>The US situation is more complicated. While federal funding is <a href="http://www.nih.gov/about-nih/who-we-are/nih-director/statements/statement-nih-funding-research-using-gene-editing-technologies-human-embryos">not presently provided</a> for germline research, no ban on private research (or, for that matter, clinical germline modification) is in place. But since the committee’s statement does not urge countries to provide national funding for germline research, it’s consistent with the US regulatory landscape.</p>
<h2>Body cells or embryos</h2>
<p>The committee statement – also in line with many current regulations – makes a careful distinction between clinical somatic cell gene therapies and germline cell therapies. So, the recent <a href="http://www.theguardian.com/science/2015/nov/05/baby-girl-is-first-in-the-world-to-be-treated-with-designer-immune-cells">infusion of genetically modified white blood cells</a> that saved the life of a baby with leukemia, Layla Richardson, would be acceptable. But it would have been unacceptable if the intervention had also affected her egg cells, and thus future children.</p>
<p>There are three important differences between the two approaches.</p>
<ol>
<li><p>Somatic therapies target genes in specific types of cells (lung cells, skin cells, blood cells, etc), while germline modifications, applied to embryos, sperm or eggs, alter the genes in all the resultant person’s cells.</p></li>
<li><p>Somatic cell modifications are noninheritable, affecting only the treated individual. Germline modifications <a href="http://www.ncbi.nlm.nih.gov/books/NBK21894/">would be passed on</a> to future generations.</p></li>
<li><p>Somatic cell therapies have been tested and implemented for <a href="http://www.ncbi.nlm.nih.gov/pubmed/23618815">much longer</a>. The first somatic trials occurred two and a half decades ago, while human germline editing studies have <a href="http://dx.doi.org/10.1007/s13238-015-0153-5">only just begun</a> this year.</p></li>
</ol>
<p>But do those differences merit a significantly different regulatory approach – a moratorium for clinical germline editing, versus standard regulation for somatic therapies? I would, in line with <a href="http://jmp.oxfordjournals.org/content/16/6/641.short">a critique</a> that appeared during the advent of somatic therapies, suggest not. </p>
<h2>Does the ethical distinction make sense?</h2>
<p>One reason for the different approaches concerns risk levels. Germline gene therapy both has greater impact and is less established than somatic gene therapy. This certainly merits more caution. Regulatory bodies should be more reluctant to approve therapies with wide-ranging, uncertain effects. It’s sensible to demand strong evidence of safety and reasonable risk/benefit ratios before new technologies are made available clinically. </p>
<p>This is the approach we take to all novel biomedical interventions. Indeed, when somatic cell therapy was first proposed, it was also a new therapy with <a href="http://www.nytimes.com/1993/09/01/health/personal-health-the-promise-and-the-pitfalls-of-gene-therapy.html">potentially severe risks</a>. <a href="http://www.fda.gov/downloads/BiologicsBloodVaccines/SafetyAvailability/UCM148113.pdf">Careful regulation</a>, rather than a blanket moratorium, was needed to manage those risks. A similar approach would make sense for germline modifications.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/104540/original/image-20151206-8664-x67jw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/104540/original/image-20151206-8664-x67jw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/104540/original/image-20151206-8664-x67jw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/104540/original/image-20151206-8664-x67jw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/104540/original/image-20151206-8664-x67jw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/104540/original/image-20151206-8664-x67jw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/104540/original/image-20151206-8664-x67jw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/104540/original/image-20151206-8664-x67jw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Does what kind of cells you’re targeting matter?</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/kaibara/3075268200">Umberto Salvagnin</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>The committee emphasizes in its statement another reason for the distinction between editing genes in the two kinds of cells. Heritability of germline changes is a novel form of risk not adequately accounted for in current regulatory frameworks. </p>
<p>However, I would argue the long-term risks of inheritability unique to germline modification are much less certain and actually more manageable than the short-term risks of harmful modifications shared by somatic therapies. The therapy used on baby Layla was the first of its kind tried in humans, and there was a serious risk of rejection that could have increased her already acute suffering. Those risks needed to be weighed heavily. But it seems unlikely that the overall risk profile would have changed significantly if the treatment would have also have affected the baby’s future children. </p>
<p>In this sort of case, there would be at least a decade and a half gap between when a modification occurs and the point at which the affected individual may begin to bear children. That’s ample time to detect abnormalities and develop mitigation strategies, including further corrective germline modification. And in any case, I’d argue it would be irresponsible to allow near-term suffering in cases like baby Layla’s in order to avoid much more uncertain long-term risks to individuals who don’t even exist yet, and may not exist but for the treatment itself.</p>
<p>A final reason for the differentiation is that some people find germline modification to be a morally objectionable form of genetic engineering. Concerns abound that it involves <a href="http://www.un.org/apps/news/story.asp?NewsID=52172#.VmKYP49OKM8">playing God</a>, <a href="http://www.councilforresponsiblegenetics.org/ViewPage.aspx?pageId=101">opens the door to eugenics</a> and will lead to <a href="http://www.huffingtonpost.com/dr-yuval-noah-harari/inequality-rich-superior-biological_b_5846794.html">a genetically stratified society</a>. </p>
<p>These objections, though, would also apply to somatic therapy. Modification of the genes in only certain cells is nevertheless still tinkering with human nature, attempting to bring about a superior genetic profile in a person. If one supports a moratorium for germline therapies on such grounds, one should also support a moratorium on somatic therapies, on similar grounds.</p>
<p>As a bioethicist, I suggest we apply the same regulatory approach to somatic gene therapy as to germline therapy. Given the much stronger evidence for the safety and efficacy of certain somatic therapies, in the near-term this will likely mean offering clinical somatic therapies and not clinical germline therapies. Or we could ban both, if one seriously objects to playing God with the human genome.</p>
<p>But carving out a separate regulatory category, as the committee statement seems to imply, is not justified.</p><img src="https://counter.theconversation.com/content/51843/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>G. Owen Schaefer does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The International Summit on Human Gene Editing drew a distinction between editing an individual’s body cells and editing germline cells that would pass changes to future generations. Does that make sense?G. Owen Schaefer, Research Fellow in Biomedical Ethics, National University of SingaporeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/514802015-12-01T19:15:45Z2015-12-01T19:15:45ZWhy we can trust scientists with the power of new gene-editing technology<figure><img src="https://images.theconversation.com/files/103829/original/image-20151201-26546-ofjsvn.png?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Gene editing allows us to eliminate any misspellings, introduce beneficial natural variants, or perhaps cut out or insert new genes. </span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/libertasacademica/7016004213/">Libertas Academica/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p><a href="http://www.nationalacademies.org/gene-editing/index.htm">A summit of experts</a> from around the world is meeting in Washington to consider the scientific, ethical and governance issues linked to research into gene editing. Convened in response to recent advances in the field, the summit includes experts from the US National Academy of Science, the UK’s Royal Society and the Chinese Academy of Science. </p>
<p><a href="https://theconversation.com/explainer-what-is-genome-editing-25072">Gene editing</a> is a new technique that allows one to change chosen genes at will. It has been applied to many organisms but <a href="http://www.ncbi.nlm.nih.gov/pubmed/25894090">a recent report</a> from China showing the modification of human embryos using a technology known as <a href="https://theconversation.com/explainer-crispr-technology-brings-precise-genetic-editing-and-raises-ethical-questions-39219">CRISPR/Cas9</a> mediated editing set alarm bells ringing. </p>
<p>Here’s the main fear: if you modify an embryo (and therefore also its germline), you change not only the person that embryo will become but also its future sons, daughters, grandsons and granddaughters. </p>
<p>Since we don’t know much about this technology, it’s right to stop and think about it. But personally I’m not overly concerned: we’ve been here – or somewhere quite like it – before. </p>
<h2>Learning from history</h2>
<p>In 1975, scientists met at Asilomar on the Californian coast to discuss a moratorium on recombinant DNA (that’s DNA formed from combining constituents from different organisms). </p>
<p>Alarm bells had started ringing when scientists realised they could combine the DNA from a monkey virus with a circle of DNA called a plasmid, carrying an antibiotic resistance gene purified from the human gut bacteria, <em>Escherichia coli</em> (<a href="http://www.about-ecoli.com/"><em>E. coli</em></a>). </p>
<p>This cocktail sounded dangerous and scientists discussed a voluntary moratorium on certain experiments, as well as sensible guidelines for containing recombinant material within laboratories. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/103830/original/image-20151201-26578-1n37bah.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/103830/original/image-20151201-26578-1n37bah.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/103830/original/image-20151201-26578-1n37bah.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/103830/original/image-20151201-26578-1n37bah.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/103830/original/image-20151201-26578-1n37bah.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/103830/original/image-20151201-26578-1n37bah.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/103830/original/image-20151201-26578-1n37bah.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Horizontal gene transfer occurs in nature when DNA is carried between species by viruses and related carriers.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/blprnt/3694704325/">Jer Thorp/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Regulations and guidelines are still in place and after 40 years few, if anyone, has been harmed by recombinant DNA. And there have been no reported outbreaks of recombinant material that have significantly affected human health or the environment. </p>
<p>All technologies, including different agricultural practices, have upsides and downsides, and most medicines and treatments have side effects. But recombinant DNA would now have to be classed among the least dangerous of scientific developments.</p>
<h2>Understanding science</h2>
<p>One reason the technology has proven so safe may be that genetic recombination has been going on for millions of years. In most cases, genes are simply passed on from parent to child. But horizontal gene transfer also occurs in nature when DNA is carried between organisms or even species by viruses. </p>
<p>Over time, DNA is naturally swapped around and moved. Though you may have eaten transgenic plant products, I very much doubt you’ve noticed.</p>
<p>There was a fear “mad scientists” would invent dangerous new superbugs and killer viruses. Perhaps this could have happened, but sadly there are enough pre-existing dangerous substances and naturally occurring diseases, which have been perfected by evolution, out there already. So germ warfare scientists are more likely to just use them.</p>
<p>Another fear was that researchers would modify humans. Most countries quickly outlawed the modification of human germ cells and, to my knowledge, it has never occurred. In general, scientists seem to have obeyed the regulations. </p>
<p>But another reason is that it has proved difficult to introduce new genes into mammalian cells. It’s legal to modify human cells, such as blood stem cells, to cure genetic diseases. But human cells are among the hardest to modify. Human “anti-viral” software seems so powerful that it inhibits the stable insertion and expression of new DNA.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/103831/original/image-20151201-26595-n1zvf7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/103831/original/image-20151201-26595-n1zvf7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=426&fit=crop&dpr=1 600w, https://images.theconversation.com/files/103831/original/image-20151201-26595-n1zvf7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=426&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/103831/original/image-20151201-26595-n1zvf7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=426&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/103831/original/image-20151201-26595-n1zvf7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=536&fit=crop&dpr=1 754w, https://images.theconversation.com/files/103831/original/image-20151201-26595-n1zvf7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=536&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/103831/original/image-20151201-26595-n1zvf7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=536&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Fears that ‘mad scientists’ would use recombinant DNA techonolgy to create superbugs like MRSA have not eventuated.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/umdnews/8161119599/in/photolist-draSwB-bhhrmR-ibEmCY-6VESwi-kGq5r8-4BwtJZ-4BAEnC-4BACiY-pBtfyG-cNTZNU-cNTZH1-cPsbUS-nVzYss-cPsc4Y-cPsbTm-cPsc1u-dV5XkT-csnK1o-csnJwo-csnJzY-csnJum-crj1db-dMgueE-5QXCmd-dMaV1V-ddaJBA-r4TfX3-csnJBs-f37psU-csnJKy-csnJG1-f3SzQs-dNZC2S-7bepH7-2Mxz5W-dNZBuf-csnJLU-csnJXj-ekEQAg-csnJNm-csnJHY-7biLPL-dNZBwm-edsrB8-e29y8j-dZtRxo-dZo9rR-dZo9bv-dZtQGW-dZtQhf">Merrill College of Journalism Press Releases</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<h2>The promise of gene editing</h2>
<p>I’m sure you’ve met people who’ve had their teeth straightened or undergone cosmetic surgery. But you’ve probably never met anyone who’s had gene therapy or ever seen a transgenic animal.</p>
<p>Could that change with gene editing? Gene editing is so precise that one doesn’t just lob in a new gene and hope it works; what one does is edit the existing gene to eliminate any misspellings, introduce beneficial natural variants, or perhaps cut out or insert new genes into chosen locations. </p>
<p>Our anti-viral software may not even detect what’s happened. And provided there aren’t any “off-target’” effects, where we hit the wrong gene, there may be no or minimal side effects.</p>
<p>Now that’s it’s so easy to meddle in human genes, why shouldn’t we worry? </p>
<p>The new technology is a game-changer – but it’s not a runaway phenomenon, like releasing cane toads, blackberries or rabbits into Australia. After 40 years, there have been few, if any problems, with genetically modified organisms. And the experiments - though much easier now - are still so elaborate and expensive that the technology will spread slowly. </p>
<p>We’ll likely remain cautious about modifying human embryos and about any modification that may be passed on to the next generation. To date, consent is required for all treatments. And while patients may opt for experimental cancer therapy or surgery, we always try to think carefully when others, who cannot consent, will be affected.</p>
<p>Some people will even ask why it’s wrong to correct a defect that could haunt future generations. Or, if we could introduce a gene variant that protects people from cancer – such as creating a duplication of the <a href="http://www.ncbi.nlm.nih.gov/books/NBK22268/">tumour suppressor gene p53</a> – why wouldn’t we want that for our children?</p>
<p>Genetics is a branch of science that’s ripe for discussions, and conversations on recombinant DNA, gene therapy, cloning and stem cells have all gone well. Guidelines have been sensible and researchers have largely complied with them. </p>
<p>The very fact that people from across the world are gathering to discuss the issues surrounding the latest breakthroughs in gene technology is a very strong sign that the science will be used responsibly. One hopes that the concurrent meeting on climate change in Paris is also a victory for science.</p><img src="https://counter.theconversation.com/content/51480/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Merlin Crossley works for the University of New South Wales. He receives funding from the National Health and Medical Research Council and the Australian Research Council. He is a Trustee of the Australian Museum, a Board Member of the Sydney Institute of Marine Science, a Council Member of the European Molecular Biology Laboratory Australia, and the Australian Science Media Centre.</span></em></p>Should the gathering of experts from around the world that’s considering the scientific, ethical, and governance issues linked to research into gene editing ring alarm bells?Merlin Crossley, Dean of Science and Professor of Molecular Biology, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/514762015-12-01T19:13:14Z2015-12-01T19:13:14ZGene editing in embryos is fraught with scientific and ethical issues<figure><img src="https://images.theconversation.com/files/103840/original/image-20151201-26549-tgy4q1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Genetic changes to embryos will not only affect the person that embryo becomes but also all their descendants.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/anniferrr/5190095551/">anna gutermuth/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span></figcaption></figure><p>Recent technological advances have revolutionised our ability to manipulate the genetic code, allowing us to specifically edit individual genes. Gene editing offers exciting potential for disease therapies but application of the technology in embryos also raises many ethical and scientific issues.</p>
<p>Humans - and all other mammals - reproduce through sperm and eggs (germ cells) that transmit a single copy of each parent’s chromosomes to the offspring. When an embryo forms at conception, it has a mix of genes from both germs cells, producing a child who’s a biological reflection of the parents.</p>
<p>Sometimes, harmful mutations or changes in a gene sequence are transmitted by the germ cells and have deleterious effects in the embryo or in later life. In recent decades, genetic screening has allowed detection of particular genetic aberrations in early embryos. This has allowed us to avoid some of the harmful consequences of specific damaging mutations through pregnancy termination. </p>
<p>While genetic screening poses complex ethical questions, it’s safe and doesn’t introduce changes to genes that affect the baby or the baby’s future children. By contrast, gene editing affects both.</p>
<h2>Risking off-target effects</h2>
<p>Gene-editing technologies have introduced the possibility of altering individual genes in eggs or sperm, or immediately after fertilisation in the earliest human embryos. This has the potential to correct gene mutations that underlie inherited disease. </p>
<p>But such germline gene therapy doesn’t only affect the individual germ cells or embryo that has been treated; any changes will be transmitted to the future children of that individual. </p>
<p>This is highly controversial as it raises major safety concerns and the spectre of introducing “designer” mutations, in which specific genetic traits could be modified according to parents’ requirements. </p>
<p>Clearly, there are fundamental social and ethical considerations involved that preclude the use of gene editing in the human germline or in human embryos. But critical questions also surround safety and the potential biological impacts of gene editing if it were to be applied in humans.</p>
<p>The most obvious risk of editing embryo genes is the potential for errors or of introducing off-target genetic effects. Off-target effects occur when gene technology mistakenly hits a DNA sequence that’s not the intended target. </p>
<p>While gene editing can be very specific, even minor errors or off-target effects are unacceptable in human embryos as they could harm the developing fetus or cause disease in adulthood. Off-target sites can also include the surprisingly large proportion of DNA sequence that lies between genes and plays important roles in gene regulation. </p>
<p>Critically, changes to any of these sequences will then be inherited by future generations.</p>
<h2>The epigenetic black box</h2>
<p>Other concerns surround potential effects on the way genes are regulated in the embryo. Although we’ve made unprecedented advances in biotechnology, we’re only beginning to understand the complex biological systems that regulate fetal formation and influence lifelong health. </p>
<p>While gene sequence is paramount, additional information provided around the DNA is also crucial for development. One such example is the epigenetic code, which controls whether the thousands of genes contained in each cell are switched on and off in the correct combination, in the correct tissue, over a lifetime. </p>
<p>Epigenetic information contained in each cell type is passed to each new cell as it divides to maintain or renew each tissue. This code ensures the long-term identity of cell types and the proper function of the tissue and organs they constitute. </p>
<p>Two important epigenetic issues arise in the context of editing embryo genes. First, environmental stimuli, such as chemicals, drugs or even diet, can alter epigenetic mechanisms. Second, disruptions in this code can lead to disease, a concept that is best illustrated in cancer development. </p>
<p>Importantly, both the sperm and egg transmit epigenetic information to the newly fertilised embryo. This epigenetic information affects development, health and even behaviour in the offspring. </p>
<p>Growing evidence indicates certain environmental stimuli alter epigenetic state in the germline and significantly affect outcomes not only in children, but also in grandchildren. Despite this, we have little understanding of how these effects are mediated in the developing embryo.</p>
<h2>Cause for caution</h2>
<p>While gene editing may be designed to correct a very specific genetic mutation, the change must be made in an embryo culture environment – that is, in the lab. Although embryo culture conditions are carefully controlled, we still have no way of properly measuring the potentially complex impacts of the gene-editing process on the embryo</p>
<p>Importantly, any negative effects may not be limited to the actual edit; they may also result from the gene-editing process, which requires the use of specific enzymes, chemicals and reagents in an artificial culture environment. These too may alter epigenetic state and other mechanisms in the embryo. </p>
<p>Despite the rapid progress and undeniable power of gene-editing technologies, we’re still in the early stages of understanding the impacts of these processes on the genetic and epigenetic state of embryos and the future health and development of the person they become. The ethical issues surrounding germline gene therapy in humans are also enormous (more on that in The Conversation tomorrow). </p>
<p>If such technology were ever to be applied to the human germline for medical purposes, these issues would need to be addressed with the greatest stringency.</p><img src="https://counter.theconversation.com/content/51476/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Patrick Western receives funding from the National Health and Medical Research Council of Australia. </span></em></p>While gene editing offers the exciting potential for disease therapies, using it on human embryos opens up a can of worms.Patrick Western, Research Group Head, Germ Cell Development and Epigenetics, Hudson InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/452562015-07-28T05:24:35Z2015-07-28T05:24:35ZWhy the case against designer babies falls apart<figure><img src="https://images.theconversation.com/files/89817/original/image-20150727-7662-mww42i.png?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">What the world is waiting for?</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-257910377/stock-photo-newborn-twin-babies-boy-and-girl.html?src=csl_recent_image-1">Hannahmariah</a></span></figcaption></figure><p>When it comes to technological advances that could reduce human suffering, improve health and reduce disease, we are generally all in favour. But recent advances in procedures that tinker with reproductive cells are often seen as an exception. They attract fierce opposition from people who believe they are unethical and should be treated as serious criminal offences – which in some jurisdictions they are already. I don’t think these arguments are decisive, however. Indeed some of them are not convincing at all. </p>
<p>Ethical debates about changing the human genome make a distinction between two different types of cells. All cells except those involved in reproduction are known as somatic. These have been the subject of less controversial research for a number of years now – for example editing a type of white blood cell known as T-cells <a href="http://www.ncbi.nlm.nih.gov/pubmed/23935598">has become</a> a major area of enquiry in cancer research. </p>
<p>Cells involved in reproduction are called germ cells. Changing them, which is sometimes described as germline editing, can have effects that can be inherited by the offspring of the people whose bodies are amended. In other words, the changes can enter the gene pool. </p>
<p>The main objections to such procedures fall into four categories: they are <a href="http://www.nature.com/news/don-t-edit-the-human-germ-line-1.17111">unpredictable and dangerous</a>; they are the slippery slope to <a href="http://biochem158.stanford.edu/FInal%20Papers%202015/Farley.pdf">eugenics and designer babies</a>; they interfere with nature and <a href="https://books.google.co.uk/books?id=hbq187NKdngC&pg=PA118&lpg=PA118&dq=germline+editing+playing+God&source=bl&ots=y7nYsVUuxT&sig=HMshV2nWt5bmxpjWSXXnLnYVdNw&hl=en&sa=X&ved=0CEsQ6AEwCGoVChMI98ac9pb7xgIVQRsUCh2g8g2w#v=onepage&q=god&f=false">involve playing God</a>; and they will <a href="http://www.geneticsandsociety.org/downloads/7_Reasons.html">exacerbate social inequality</a> and cause a division between the genetically enhanced and the rest of us.</p>
<h2>First among equals</h2>
<p>To begin with, not everything that leads to social inequality is unethical. And even in instances when such practices are unethical, it doesn’t automatically follow that they should be illegal. </p>
<p>For instance, it is clearly arguable that any advanced system of higher education might perpetuate social inequality. Those who succeed in their studies might tend to get better jobs than people who are less educated. And the children of parents who are highly educated <a href="http://www.theguardian.com/education/2010/apr/26/university-school-grades-child-background">are more likely</a> to become highly educated than other children. But very few would argue that this makes higher education or indeed family units unethical. Neither do we normally say that scientific research should be undertaken only if won’t lead to social inequality and divisiveness. It is whimsical to attach such a requirement in the case of genome editing. </p>
<p>As for the course of nature, we alter it when we dam a stream or build a house. We play God if we inoculate a child against polio or operate upon a baby with a hole in her heart rather than watch her die. If we could edit a germline such that these possibilities were permanently eradicated, why shouldn’t we consider doing so? We play God when we consider it reasonable and so we should.</p>
<p>You have to consider the ethics of acts of omission in this context. It is wrong to push someone off a cliff. But it is also sometimes wrong to fail to prevent someone from accidentally falling off a cliff. In the same way, it would surely be wrong to deliberately edit a germline so that someone who would have lived a long and healthy life will lead a short, miserable one. But what about the reverse? What if we could deliberately edit a germline to lengthen someone’s life expectancy and make them healthier? Would we not have an ethical obligation to do so? And surely if their descendants would also enjoy the same benefits, the duty to intervene becomes even stronger. </p>
<p>Indeed you can turn the question around and say: if one could design healthy babies, what would be the moral justification for failing to do so? It is not obvious that there is one. The term “designer baby” is emotive, pejorative and misleading. But if there is a slope that leads to them, we should perhaps edge along it carefully. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/89815/original/image-20150727-7653-1ygxfmj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/89815/original/image-20150727-7653-1ygxfmj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/89815/original/image-20150727-7653-1ygxfmj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/89815/original/image-20150727-7653-1ygxfmj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/89815/original/image-20150727-7653-1ygxfmj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/89815/original/image-20150727-7653-1ygxfmj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/89815/original/image-20150727-7653-1ygxfmj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/89815/original/image-20150727-7653-1ygxfmj.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 next Einstein, you say?’</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/s/cloning/search.html?page=6&thumb_size=mosaic&inline=224787508">Nevodka</a></span>
</figcaption>
</figure>
<h2>Risks and rewards</h2>
<p>This brings us to the fourth common objection. Several prominent scientists <a href="http://www.nature.com/news/don-t-edit-the-human-germ-line-1.17111">argued in Nature</a> in March that there were “serious risks” around editing germ cells. They wrote: </p>
<blockquote>
<p>In our view, genome editing in human embryos using current technologies could have unpredictable effects on future generations. This makes it dangerous and ethically unacceptable.</p>
</blockquote>
<p>They argued that it may be impossible to know the precise effects of modifying an embryo until after birth. I would readily accept that. Yet risk and uncertainty are different concepts. Germline editing might be as likely to produce unpredicted benefits as harms. It does not follow that it is dangerous. It is, rather, uncertain. </p>
<p>The precise effects of failing to proceed with germline editing can be uncertain too. We are far from certain that developing such procedures will be more dangerous than avoiding them. And in some cases we can be pretty sure that some people will otherwise either die or only survive in pain, illness or incapacity. If we know that the absence of genetic editing is dangerous, why shun it? Surely we have a moral duty to do the opposite.</p>
<p>Finally, think about what happens with normal childbirth. In such situations, the genetic outcomes are generally not known until after birth. It does not follow that normal childbirth is dangerous, however. Even when it is dangerous and risky, it does not follow that it is unethical – nor of course that it should be illegal. </p>
<p>Equally it is far from clear that germ editing is dangerous. Even if it were, it does not follow that it is unethical or that it should be banned. For too long we have allowed religious groups and other well meaning people to prevent us from exploring avenues that are potentially vital to human progress with arguments that range from questionable to completely wrong. It is time we moved away from absolute bans and started focusing on how to mitigate the dangers and risks instead.</p><img src="https://counter.theconversation.com/content/45256/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Hugh McLachlan 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>Since science made it possible to research manipulating the cells that are linked to reproduction, the naysayers have carried the day. But how solid are their objections really?Hugh McLachlan, Professor of Applied Philosophy, Glasgow Caledonian UniversityLicensed as Creative Commons – attribution, no derivatives.