tag:theconversation.com,2011:/africa/topics/gene-editing-18986/articlesGene editing – The Conversation2024-03-27T19:07:40Ztag:theconversation.com,2011:article/2263932024-03-27T19:07:40Z2024-03-27T19:07:40ZThe first pig kidney has been transplanted into a living person. But we’re still a long way from solving organ shortages<figure><img src="https://images.theconversation.com/files/584634/original/file-20240327-22-zkx0ie.jpg?ixlib=rb-1.1.0&rect=0%2C73%2C8192%2C5383&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.massgeneral.org/news/press-release/worlds-first-genetically-edited-pig-kidney-transplant-into-living-recipient">Massachusetts General Hospital</a></span></figcaption></figure><p>In a world first, we heard last week that US surgeons had transplanted a kidney from a gene-edited pig into a living human. News reports said the procedure was <a href="https://www.npr.org/sections/health-shots/2024/03/21/1239790816/first-pig-kidney-human-transplant">a breakthrough</a> in xenotransplantation – when an organ, cells or tissues are transplanted from one species to another.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/cisOFfBPZk0?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The world’s first transplant of a gene-edited pig kidney into a live human was announced last week.</span></figcaption>
</figure>
<p>Champions of xenotransplantation regard it as <em>the</em> solution to organ shortages across the world. In December 2023, <a href="https://www.anzdata.org.au/anzod/publications-2/organ-waiting-list/">1,445 people</a> in Australia were on the waiting list for donor kidneys. In the United States, more than <a href="https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/">89,000</a> are waiting for kidneys. </p>
<p>One biotech CEO says gene-edited pigs <a href="https://www.technologyreview.com/2015/08/12/248193/surgeons-smash-records-with-pig-to-primate-organ-transplants/">promise</a> “an unlimited supply of transplantable organs”.</p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6452271/">Not</a>, <a href="https://theconversation.com/organ-transplants-from-pigs-medical-miracle-or-pandemic-in-the-making-175290">everyone</a>, though, <a href="https://onlinelibrary.wiley.com/doi/10.1111/imj.13183">is convinced</a> transplanting animal organs into humans is really the answer to organ shortages, or even if it’s right to use organs from other animals this way.</p>
<p>There are two critical barriers to the procedure’s success: organ rejection and the transmission of <a href="https://journals.sagepub.com/doi/epdf/10.1177/09636897241226849">animal viruses to recipients</a>. </p>
<p>But in the past decade, a new platform and technique known as CRISPR/Cas9 – often shortened to CRISPR – has promised to mitigate these issues.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/organ-transplants-from-pigs-medical-miracle-or-pandemic-in-the-making-175290">Organ transplants from pigs: Medical miracle or pandemic in the making?</a>
</strong>
</em>
</p>
<hr>
<h2>What is CRISPR?</h2>
<p>CRISPR gene editing takes advantage of a system already found in nature. CRISPR’s “genetic scissors” evolved in bacteria and other microbes to help them fend off viruses. Their cellular machinery <a href="https://www.sciencedirect.com/science/article/pii/S0300908415001042#:%7E:text=The%20system%2C%20called%20CRISPR%2DCas,remember%2C%20recognize%20and%20clear%20infections.">allows them</a> to integrate and ultimately destroy viral DNA by cutting it.</p>
<p>In 2012, two teams of scientists <a href="https://www.science.org/doi/10.1126/science.1225829">discovered how to harness</a> this bacterial immune system. This is made up of repeating arrays of DNA and associated proteins, known as “Cas” (CRISPR-associated) proteins. </p>
<p>When they used a particular Cas protein (Cas9) with a “guide RNA” made up of a singular molecule, they found they could <a href="https://pubmed.ncbi.nlm.nih.gov/22745249/">program</a> the CRISPR/Cas9 complex to break and repair DNA at precise locations as they desired. The system could even “knock in” new genes at the repair site. </p>
<p>In 2020, the two scientists leading these teams were awarded a <a href="https://www.nobelprize.org/prizes/chemistry/2020/summary/">Nobel prize</a> for their work.</p>
<p>In the case of the latest xenotransplantation, CRISPR technology was used to <a href="https://www.massgeneral.org/news/press-release/worlds-first-genetically-edited-pig-kidney-transplant-into-living-recipient">edit 69 genes</a> in the donor pig to inactivate viral genes, “humanise” the pig with human genes, and knock out harmful pig genes.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/UKbrwPL3wXE?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">How does CRISPR work?</span></figcaption>
</figure>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/what-is-crispr-the-gene-editing-technology-that-won-the-chemistry-nobel-prize-147695">What is CRISPR, the gene editing technology that won the Chemistry Nobel prize?</a>
</strong>
</em>
</p>
<hr>
<h2>A busy time for gene-edited xenotransplantation</h2>
<p>While CRISPR editing has brought new hope to the possibility of xenotransplantation, even recent trials show great caution is still warranted.</p>
<p>In 2022 and 2023, two patients with <a href="https://www.medschool.umaryland.edu/news/2023/um-medicine-faculty-scientists-and-clinicians-perform-second-historic-transplant-of-pig-heart-into-patient-with-end-stage-cardiovascular-disease.html#:%7E:text=The%20first%20historic%20surgery%2C%20performed,had%20end%2Dstage%20heart%20disease.">terminal heart diseases</a>, who were ineligible for traditional heart transplants, were granted <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00775-4/abstract">regulatory permission</a> to receive a gene-edited pig heart. These pig hearts had ten genome edits to make them more suitable for transplanting into humans. However, both patients died within several weeks of the procedures. </p>
<p>Earlier this month, we heard a team of surgeons in China transplanted a gene-edited pig liver into a <a href="https://www.nature.com/articles/d41586-024-00853-8">clinically dead man</a> (with family consent). The liver functioned well up until the ten-day limit of the trial.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/you-donate-your-body-to-science-you-die-what-happens-next-1481">You donate your body to science, you die ... what happens next?</a>
</strong>
</em>
</p>
<hr>
<h2>How is this latest example different?</h2>
<p>The gene-edited pig kidney <a href="https://www.massgeneral.org/news/kidney-xenotransplant-faqs">was transplanted</a> into a relatively young, living, legally competent and consenting adult.</p>
<p>The total number of gene edits edits made to the donor pig is very high. The researchers report making <a href="https://www.nature.com/articles/d41586-024-00879-y">69 edits</a> to inactivate viral genes, “humanise” the pig with human genes, and to knockout harmful pig genes.</p>
<p>Clearly, the race to transform these organs into viable products for transplantation is ramping up.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/what-are-uterus-transplants-who-donates-their-uterus-and-what-are-the-risks-190443">What are uterus transplants? Who donates their uterus? And what are the risks?</a>
</strong>
</em>
</p>
<hr>
<h2>From biotech dream to clinical reality</h2>
<p>Only a few months ago, CRISPR gene editing made its debut in mainstream medicine. </p>
<p>In November, drug regulators in the <a href="https://www.gov.uk/government/news/mhra-authorises-world-first-gene-therapy-that-aims-to-cure-sickle-cell-disease-and-transfusion-dependent-thalassemia">United Kingdom</a> and <a href="https://www.fda.gov/media/174618/download?attachment">US</a> approved the world’s first CRISPR-based genome-editing therapy for human use – a treatment for life-threatening forms of sickle-cell disease. </p>
<p>The treatment, known as <a href="https://sicklecellanemianews.com/ctx001-sickle-cell-disease">Casgevy</a>, uses CRISPR/Cas-9 to edit the patient’s own blood (bone-marrow) stem cells. By disrupting the <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2029392">unhealthy gene</a> that gives red blood cells their “sickle” shape, the aim is to produce red blood cells with a healthy spherical shape. </p>
<p>Although the treatment uses the patient’s own cells, the same underlying principle applies to recent clinical xenotransplants: unsuitable cellular materials may be edited to make them therapeutically beneficial in the patient.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Sickle cells have a different shape to healthy round red blood cells" src="https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=337&fit=crop&dpr=1 600w, https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=337&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=337&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">CRISPR technology is aiming to restore diseased red blood cells to their healthy round shape.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-rendered-medical-illustration-sickle-cell-2221001799">Sebastian Kaulitzki/Shutterstock</a></span>
</figcaption>
</figure>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/organs-too-risky-to-donate-may-be-safer-than-we-think-we-crunched-the-numbers-and-heres-what-we-found-124993">Organs 'too risky' to donate may be safer than we think. We crunched the numbers and here's what we found</a>
</strong>
</em>
</p>
<hr>
<h2>We’ll be talking more about gene-editing</h2>
<p>Medicine and gene technology regulators are increasingly asked to <a href="https://www.utas.edu.au/__data/assets/pdf_file/0011/1634258/OP12-final-report.pdf">approve new experimental trials</a> using gene editing and CRISPR.</p>
<p>However, neither xenotransplantation nor the therapeutic applications of this technology lead to changes to the genome that can be inherited.</p>
<p>For this to occur, CRISPR edits would need to be applied to the cells at the earliest stages of their life, such as to <a href="https://doi.org/10.1089/crispr.2020.0082">early-stage embryonic cells</a> in vitro (in the lab). </p>
<p>In Australia, intentionally creating heritable alterations to the human genome is a criminal offence carrying <a href="https://classic.austlii.edu.au/au/legis/cth/consol_act/pohcfra2002465/s15.html">15 years’ imprisonment</a>. </p>
<p><a href="https://www.utas.edu.au/__data/assets/pdf_file/0011/1634258/OP12-final-report.pdf">No jurisdiction in the world</a> has laws that <a href="https://doi.org/10.1089/crispr.2020.0082">expressly permits</a> heritable human genome editing. However, some <a href="https://crispr-gene-editing-regs-tracker.geneticliteracyproject.org/russia-germline-embryonic/">countries</a> lack specific regulations about the procedure.</p>
<h2>Is this the future?</h2>
<p>Even without creating inheritable gene changes, however, xenotransplantation using CRISPR is in its infancy.</p>
<p>For all the promise of the headlines, there is not yet one example of a stable xenotransplantation in a living human lasting <a href="https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.03060/full">beyond seven months</a>. </p>
<p>While authorisation for this recent US transplant has been granted under the so-called “compassionate use” <a href="https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=312.310">exemption</a>, conventional clinical trials of pig-human xenotransplantation have yet to commence. </p>
<p>But the prospect of such trials would likely require significant improvements in current outcomes to gain regulatory approval <a href="https://www.fda.gov/media/102126/download">in the US</a> or <a href="https://iris.who.int/bitstream/handle/10665/341817/WHO-HTP-EHT-CPR-2011.01-eng.pdf?sequence=1&isAllowed=y">elsewhere</a>. </p>
<p>By the same token, regulatory approval of any “off-the-shelf” xenotransplantation organs, including gene-edited kidneys, would seem <a href="https://link.springer.com/chapter/10.1007/978-981-99-7691-1_24">some way off</a>.</p><img src="https://counter.theconversation.com/content/226393/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Christopher Rudge was a member of a research team that designed and convened an Australian citizens' jury on genome editing in 2021-22. This was funded by the Medical Research Future Fund.</span></em></p>Champions of xenotransplantation see it as the solution to organ shortages across the world. But this technology has other applications.Christopher Rudge, Law lecturer, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2196372023-12-15T14:09:29Z2023-12-15T14:09:29ZGenetically modified crops aren’t a solution to climate change, despite what the biotech industry says<figure><img src="https://images.theconversation.com/files/564970/original/file-20231211-18-xfrqe8.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C3319%2C2383&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Barbara Van Dyck</span></span></figcaption></figure><p>The European Commission launched a <a href="https://food.ec.europa.eu/plants/genetically-modified-organisms/new-techniques-biotechnology_en">proposal</a> in July 2023 to deregulate a large number of plants manufactured using new genetic techniques. </p>
<p>Despite extraordinary attempts by the Spanish presidency to force a breakthrough, EU members have not yet reached a consensus on this plan. But if the proposal were to be approved, these plants would be treated the same as conventional plants, eliminating the need for safety tests and the labelling of genetically modified food products. </p>
<p>The European public <a href="https://journals.sagepub.com/doi/full/10.1177/25148486211042307">has refused</a> to blindly accept genetically modified food from the moment the technology was developed, largely due to concerns about corporate control, health and the environment. </p>
<p>Biotech firms have been trying to sell genetically modified crops to Europeans for decades. But <a href="https://extranet.greens-efa.eu/public/media/file/1/6910">most European citizens</a> remain convinced that crops made with both old and new genetic techniques should be tested and labelled.</p>
<p>So, where has this proposal come from? Biotech firms seem to have succeeded in convincing the European Commission that we need new genetically modified crops to tackle climate change. They <a href="https://croplife.org/wp-content/uploads/2022/10/Potential-Impact-of-Genome-Editing-on-Climate-Adaptation-and-Mitigation_FINAL.pdf">argue</a> that by enhancing crops’ resistance to drought or improving their ability to capture carbon, climate change may no longer seem such a daunting challenge. </p>
<p>If this seems too good to be true, unfortunately, it is. Biotech firms have taken advantage of growing concerns about climate change to influence the European Commission with an orchestrated <a href="https://corporateeurope.org/en/2021/03/derailing-eu-rules-new-gmos">lobbying campaign</a>.</p>
<figure class="align-center ">
<img alt="Green sprout soy growing in soil." src="https://images.theconversation.com/files/565444/original/file-20231213-25-cemqd7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/565444/original/file-20231213-25-cemqd7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=287&fit=crop&dpr=1 600w, https://images.theconversation.com/files/565444/original/file-20231213-25-cemqd7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=287&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/565444/original/file-20231213-25-cemqd7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=287&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/565444/original/file-20231213-25-cemqd7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=361&fit=crop&dpr=1 754w, https://images.theconversation.com/files/565444/original/file-20231213-25-cemqd7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=361&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/565444/original/file-20231213-25-cemqd7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=361&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The EU Council has rejected compromise over genetically modified crop regulation reform.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/green-sprout-soy-growing-fertile-soil-2277106953">Ruslan Khismatov/Shutterstock</a></span>
</figcaption>
</figure>
<h2>Climate goals as PR strategy</h2>
<p>In 2018, the European Court <a href="https://curia.europa.eu/jcms/upload/docs/application/pdf/2018-07/cp180111en.pdf">ruled</a> that plants made with new genetic techniques have to be regulated like any other genetically modified organism. Biotech firms and their <a href="https://corporateeurope.org/en/2023/04/dutch-biotech-researchers-conflicting-roles-lobby-deregulation-new-gmos">allies</a> within biotech research centres have since set out to convince the European Commission of the need for an entirely new legislation.</p>
<p>The first step was to rebrand the techniques they are using, aiming to distance themselves from the bad reputation of genetic modification. Biotech firms started to use more <a href="https://www.tandfonline.com/doi/pdf/10.1080/15487733.2020.1816687%40tsus20.2020.17.issue-S2">innocent terms</a> like gene editing and precision breeding instead. </p>
<p>They then argued that their processes are not really any different from what happens in nature, portraying them as an <a href="https://www.europabio.org/wp-content/uploads/2021/03/2019_06_G_PP_EuropaBio-Updated-genome-editing-paper.pdf">advanced version of natural processes</a>. Biotech firms need this argument to eliminate the requirement for labelling, which serves as a barrier for selling their products in a climate of public disapproval. </p>
<p>In a third step, they leveraged the urgency of the climate crisis to argue that we cannot afford time-consuming safety tests. They contended that such tests would <a href="https://www.eu-sage.eu/sites/default/files/2021-03/EU-SAGE%20EC%20letter%20February%202021.pdf">hinder innovation</a> in a period of accelerating climate change.</p>
<p>There are <a href="https://newgmo.org/">several flaws</a> in this approach. The terms “gene editing” or “precision breeding” may sound more reassuring, but we argue they are essentially marketing terms and say nothing about the accuracy of the techniques used or their potentially negative effects.</p>
<p><a href="https://www.testbiotech.org/content/joint-statement-scientists-future-eu-regulation-ngt-plants-perspective-protection-goals">Studies</a> have shown that new genetic techniques can alter the traits of a species “to an extent that would be impossible, or at least very unlikely, using conventional breeding”. They can also trigger substantial <a href="https://pubmed.ncbi.nlm.nih.gov/36365450/">unintended changes</a> in the genetic material of plants. </p>
<p>But, perhaps most importantly, genetically modified plants aren’t the solution to the climate crisis. They are a false solution that starts from the wrong question. </p>
<h2>False promises</h2>
<p>It is well known that our current agricultural model <a href="https://ipes-food.org/_img/upload/files/UniformityToDiversity_FULL.pdf">contributes</a> significantly to climate change. The development of genetically modified crops is being steered largely by the very same agro-chemical giants that established and control this form of agriculture. </p>
<p>Companies like Corteva and Bayer (which acquired US agrochemical company Monsanto in 2018) are leading the race to secure patents on new genetic techniques and their products. </p>
<p>Typical examples include <a href="https://www.bafu.admin.ch/dam/bafu/de/dokumente/biotechnologie/externe-studien-berichte/endbericht-semnar-gelinsky.pdf.download.pdf/endbericht-semnar-gelinsky.pdf">patents</a> for soybeans with increased protein content, waxy corn, or rice that is tolerant to herbicides. These crops are designed for an agricultural model centred on the large-scale cultivation of single crop varieties destined for the global market. </p>
<p>This agricultural model relies on staggering amounts of fuel for distribution and places farmers in a state of dependence on heavy machinery and farm inputs (like artificial fertilisers and pesticides) derived from fossil fuels. </p>
<p>Research has found that farming in this way causes <a href="https://ehp.niehs.nih.gov/doi/abs/10.1289/ehp.02110445">soil depletion</a> and <a href="https://www.sciencedirect.com/science/article/abs/pii/S0006320718313636">biodiversity loss</a>. It also increases <a href="https://ipes-food.org/_img/upload/files/UniformityToDiversity_FULL.pdf">vulnerability</a> to pests and diseases, necessitating the development of different and potentially more toxic pesticides and herbicides. </p>
<p>Although biotech firms are playing the climate card, only a <a href="https://www.preprints.org/manuscript/202311.1897/v1/download">small proportion</a> of the genetically modified crops being developed deal with concerns related to the climate. In fact, the climate credentials of many of these crops are questionable. Modifications such as an increased shelf life, or being better able to withstand being transported are merely intended to smooth the operation of our unsustainable food system. </p>
<p>Rather than strengthening our unsustainable agricultural model, the focus should be on restoring what industrial agriculture has destroyed: farmers’ livelihoods, biodiversity and soil health. Only then will farmers be able to cultivate local climates that naturally store carbon and provide optimal conditions for <a href="https://www.fao.org/3/cb0486en/cb0486en.pdf">food production</a> without placing so much pressure on the environment.</p>
<figure class="align-center ">
<img alt="Tractor spraying pesticides on a soy field." src="https://images.theconversation.com/files/565436/original/file-20231213-21-9rpgqu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/565436/original/file-20231213-21-9rpgqu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=362&fit=crop&dpr=1 600w, https://images.theconversation.com/files/565436/original/file-20231213-21-9rpgqu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=362&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/565436/original/file-20231213-21-9rpgqu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=362&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/565436/original/file-20231213-21-9rpgqu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=455&fit=crop&dpr=1 754w, https://images.theconversation.com/files/565436/original/file-20231213-21-9rpgqu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=455&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/565436/original/file-20231213-21-9rpgqu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=455&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Our current agricultural model centres on the large-scale cultivation of single crop varieties.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/tractor-spraying-pesticides-on-soy-field-1908369397">Fotokostic/Shutterstock</a></span>
</figcaption>
</figure>
<h2>Paying the price</h2>
<p>Biotech firms advocate a no-testing policy as they argue that new genetically modified crops would be safe. But there is a problem. The legislation proposed by the European Commission eliminates the possibility of ever <a href="https://ensser.org/publications/2023/statement-eu-commissions-proposal-on-new-gm-plants-no-science-no-safety/">finding out</a> if these claims are correct. </p>
<p>Health and environmental problems are often the result of complex, interacting and largely invisible causes. As tracing and labelling won’t be mandatory, it will be very difficult to trace any adverse outcomes back to their causes. </p>
<p>Ultimately, people and the planet will pay the price when untested genetically modified crops penetrate our environments and the food chain. </p>
<p><em>In response to this article, a spokesperson from the American Seed Trade Association said plant breeders need all the tools at their disposal to provide improved plant varieties to farmers so they can continue producing in a challenging environment. The Association said there is consensus among plant breeders and regulatory bodies that innovative techniques, like genome editing, can be safely integrated into breeding programmes to develop plant varieties that are indistinguishable from those developed through conventional breeding. Bayer and Corteva were contacted for a comment on the issues raised in this article, but had not provided any by the time of publication.</em></p>
<hr>
<figure class="align-right ">
<img alt="Imagine weekly climate newsletter" src="https://images.theconversation.com/files/434988/original/file-20211201-21-13avx6y.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/434988/original/file-20211201-21-13avx6y.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/434988/original/file-20211201-21-13avx6y.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/434988/original/file-20211201-21-13avx6y.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/434988/original/file-20211201-21-13avx6y.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/434988/original/file-20211201-21-13avx6y.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/434988/original/file-20211201-21-13avx6y.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
</figcaption>
</figure>
<p><strong><em>Don’t have time to read about climate change as much as you’d like?</em></strong>
<br><em><a href="https://theconversation.com/uk/newsletters/imagine-57?utm_source=TCUK&utm_medium=linkback&utm_campaign=Imagine&utm_content=DontHaveTimeTop">Get a weekly roundup in your inbox instead.</a> Every Wednesday, The Conversation’s environment editor writes Imagine, a short email that goes a little deeper into just one climate issue. <a href="https://theconversation.com/uk/newsletters/imagine-57?utm_source=TCUK&utm_medium=linkback&utm_campaign=Imagine&utm_content=DontHaveTimeBottom">Join the 20,000+ readers who’ve subscribed so far.</a></em></p>
<hr><img src="https://counter.theconversation.com/content/219637/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Biotech firms are using climate goals opportunistically in an attempt to force through the deregulation of genetically modified crops.Anneleen Kenis, Lecturer in Political Ecology and Environmental Justice, Brunel University LondonBarbara Van Dyck, Research Fellow in Political Agroecology, Université Libre de Bruxelles (ULB)Licensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2168762023-11-08T14:09:06Z2023-11-08T14:09:06ZCan HIV be cured using gene editing? We will soon find out<figure><img src="https://images.theconversation.com/files/558029/original/file-20231107-23-m91tyr.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5668%2C3937&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/editing-dna-chains-concept-genome-modification-2375332825">Andrii Yalanskyi/Shutterstock</a></span></figcaption></figure><p>HIV, the virus that causes Aids, was first <a href="https://www.who.int/news-room/spotlight/why-the-hiv-epidemic-is-not-over#:%7E:text=The%20HIV%20virus%20was%20first,situation%20and%20initiated%20international%20surveillance.">identified in 1983</a>. To catch this virus was initially a death sentence, but today, thanks to antiretroviral drugs, it can be kept in check. However, there is still no cure. </p>
<p>A small biotech company in San Francisco called Excision BioTherapeutics is trying to change that with its infusion, called EBT-101. The company <a href="https://www.globenewswire.com/news-release/2023/10/25/2766525/0/en/Excision-BioTherapeutics-Presents-Positive-Interim-Clinical-Data-from-Ongoing-Phase-1-2-Trial-of-EBT-101-for-the-Treatment-of-HIV-at-ESGCT-30th-Annual-Congress.html">recently reported</a> positive results on the one-off gene-editing treatment – but only regarding safety. There were no severe side-effects in the three patients given the experimental drug. </p>
<p>We will have to wait till 2024 for the first report on efficacy.</p>
<p>Despite the availability of antiretroviral drugs, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8864516/">hundreds of thousands</a> of people still die from Aids each year. A cure for the disease is sorely needed.</p>
<h2>Small but wily</h2>
<p>HIV, like all viruses, is made of genetic material and a shell. It is about a quadrillion times <a href="https://www.pnas.org/doi/10.1073/pnas.2303077120">smaller than a human body</a> and is an expert at dodging the immune system’s defences. </p>
<p>The treatment developed by Excision BioTherapeutics uses <a href="https://theconversation.com/nobel-prize-two-women-share-chemistry-prize-for-the-first-time-for-work-on-genetic-scissors-147721">gene-editing technology called Crispr</a> to seek out and disable the virus by cutting large sections of its DNA, which prevents it from replicating.</p>
<p>Crispr is an idea copied from our microscopic ancestors, the bacterial cells. This versatile tool against viruses, efficiently used by bacteria for millions of years to defend themselves, is now ready to protect humans from viral threats. </p>
<p>Crispr is like a miniature robot that can be directed to desired locations on genetic material within a living cell or outside. It can be used for <a href="https://www.frontiersin.org/articles/10.3389/fcell.2021.699597/full">curing diseases</a>, developing <a href="https://www.synthego.com/blog/crispr-agriculture-foods#:%7E:text=CRISPR%20gene%20editing%20technology%20has,to%20a%20store%20near%20you.">new types of crops</a>, and keeping an eye on how infectious <a href="https://www.nature.com/articles/s41551-021-00760-7">diseases spread</a>.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/UKbrwPL3wXE?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">How Crispr works.</span></figcaption>
</figure>
<p>It has been 35 years since Crispr was <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5847661/">first discovered</a>, but in the last ten years, the technology has made significant progress, especially in treating inherited diseases, such as <a href="https://www.npr.org/sections/health-shots/2023/03/16/1163104822/crispr-gene-editing-sickle-cell-success-cost-ethics">sickle cell disease</a>. The US Food and Drug Administration is expected to decide on the approval of Crispr for sickle cell therapy in December.</p>
<h2>We need a cure</h2>
<p>As of December 2022, nearly 30 million people were receiving antiretroviral drugs for HIV, which is a significant increase from 7.7 million in <a href="https://www.un.org/en/global-issues/aids#:%7E:text=Since%20the%20start%20of%20the,million%20people%20living%20with%20HIV.">2010</a>. Although these drugs are life-savers, they can induce side-effects, such as blocked arteries of the <a href="https://hivinfo.nih.gov/understanding-hiv/fact-sheets/hiv-and-heart-disease">heart</a> and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952282/">neurodegenerative disorders</a>.</p>
<p>Viruses and the organisms they infect have been at war for billions of years. The human body is a fortress guarded by layers of protection, so HIV uses several tactics to escape the sophisticated immune attack of the human body. One strategy is to remain hidden within the very same immune cells, called <a href="https://news.weill.cornell.edu/news/2020/04/hiv-hides-in-immune-system-cells-resistant-to-killer-t-cells">T cells</a>, that are designed to attack it. The virus can remain dormant in these cells for long periods, waiting for suitable conditions <a href="https://www.nih.gov/news-events/nih-research-matters/new-strategies-drive-hiv-cellular-hiding-places">to replicate</a>.</p>
<p>The virus also makes mistakes in its genetic material when replicating, giving rise to thousands of mutant varieties. This makes it very <a href="https://www.who.int/news-room/fact-sheets/detail/hiv-drug-resistance">difficult to develop drugs</a> against the threatening disease. However, Crispr is designed to attack the core of the virus, increasing the chance of disabling it.</p>
<p>Researchers have been focusing on enhancing Crispr tools and their delivery to HIV-infected cells to directly target and remove the integrated viral DNA from the host <a href="https://www.nature.com/articles/s41467-022-29346-w">immune cell’s</a> genome. </p>
<h2>From animals to humans</h2>
<p>As with all drugs, the treatment first had to be tested in lab animals. </p>
<p><a href="https://pubmed.ncbi.nlm.nih.gov/33247091/">In 2020</a> researchers at Temple University in the US successfully used Crispr to seek out HIV in the organs of mice and rats and remove critical bits of HIV DNA. This boosted further research in the field. </p>
<p>In the same year, the same team <a href="https://www.nature.com/articles/s41467-020-19821-7">provided proof</a> that the technique worked in macaques with the simian (monkey) form of HIV, known as SIV. This suggested that the treatment might be safe to test in humans.</p>
<p>While the safety results of EBT-101 are encouraging, there is still a lot of work to do. Testing on larger groups of people and making the therapy affordable for everyone with HIV are crucial because the disease is more prevalent in poorer countries. </p>
<p>Still, the accomplishment of Excision BioTherapeutics is starting to give hope that a cure for Aids may be on the horizon.</p><img src="https://counter.theconversation.com/content/216876/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kalpana Surendranath 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>Science is getting closer to finding a cure for HIV.Kalpana Surendranath, Senior Lecturer in Molecular biology and Microbiology, Leader of Genome Engineering Lab, University of WestminsterLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2166492023-11-02T14:20:44Z2023-11-02T14:20:44ZBird flu could be eradicated by editing the genes of chickens - our study shows how<p>Recent advances in gene editing technology could potentially be used to create disease-resistant animals. This could curtail the spread of avian influenza, commonly known as bird flu. </p>
<p>In a recent <a href="https://www.nature.com/articles/s41467-023-41476-3">gene editing</a> study, my colleagues and I showcased the potential of gene editing to protect chickens from the threat of bird flu. This disease is caused by an ever-evolving virus that gets around numerous <a href="https://www.daera-ni.gov.uk/articles/biosecurity#:%7E:text=Biosecurity%20is%20the%20prevention%20of,quality%20of%20a%20food%20product.">biosecurity</a> measures such as good hygiene, restricting bird movements, surveillance through appropriate testing, and selective elimination of infected birds.</p>
<p>A gene editing breakthrough would stem the huge economic losses currently suffered as a result of bird flu outbreaks. It would also be a significant step in controlling a disease that can cause serious sickness and death in humans.</p>
<h2>Why managing bird flu matters</h2>
<p>Outbreaks of bird flu around the world cost <a href="https://www.nature.com/articles/d41586-022-03322-2">billions of dollars</a> in losses. The United States Department of Agriculture reported that up to <a href="https://www.reuters.com/business/healthcare-pharmaceuticals/avian-flu-outbreak-wipes-out-5054-mln-us-birds-record-2022-11-24/">50 million birds</a> died from bird flu in 2022. Recently, the South African Poultry Association said more than <a href="https://www.thepoultrysite.com/news/2023/10/avian-influenza-forces-south-africa-to-cull-2-5-million-broilers">7 million</a> chickens were destroyed after outbreaks were detected in the first half of 2023.</p>
<p>Beyond the economic implications, bird flu outbreaks also pose a risk to <a href="https://www.who.int/news/item/12-07-%202023-ongoing-avian-influenza-outbreaks-in-animals-pose-risk-to-humans">human health</a>.</p>
<p>Prior to the COVID-19 pandemic, bird flu was considered a possible trigger for a devastating human pandemic. This prompted international surveillance led by the <a href="https://www.woah.org/en/home/">World Organisation for Animal Health</a>, the <a href="https://www.who.int/">World Health Organization</a> and the <a href="https://www.fao.org/home/en">Food and Agricultural Organisation of the United Nations</a>.</p>
<p>The fear is well-founded as the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291411/#:%7E:text=Three%20worldwide%20(pandemic)%20outbreaks%20of,and%20Hong%20Kong%20influenza%2C%20respectively.">three flu pandemics</a> of the 20th century – including the <a href="https://www.cdc.gov/flu/avianflu/timeline/avian-timeline-1880-1959.htm">1918 flu pandemic</a> that
claimed tens of millions of lives – originated from birds.</p>
<h2>Vaccinations can only do so much</h2>
<p>Vaccination is a primary method for preventing bird flu outbreaks in chickens. </p>
<p>However, the effectiveness of vaccines is limited because the bird flu virus rapidly evolves. This makes existing vaccines less effective over time. Also, there are multiple strains of the bird flu virus but a vaccine is effective against a specific strain only. </p>
<p>It’s necessary to match a <a href="https://doi.org/10.2903/j.efsa.2023.8271">vaccine</a> with the prevailing strain causing an outbreak. Using vaccines may also involve substantial costs and practical hurdles of distribution.</p>
<h2>Gene editing to improve animal welfare</h2>
<p>In contrast to vaccinations, gene editing targets a protein or proteins within chickens that are vital for all strains of bird flu, effectively stopping the virus in its tracks.</p>
<p>Gene editing refers to the process of making a precise change in a specific gene in an animal to introduce <a href="https://genomebiology.biomedcentral.com/articles/10.1186/s13059-018-1583-1">traits</a> such as resistance to a particular disease, increased productivity and characteristics that enhance animal welfare. </p>
<p>A beneficial genetic change introduced into an animal using gene editing may already occur naturally in another animal. </p>
<p>For example, gene editing was used to make dairy cattle hornless by introducing into them a <a href="https://www.nature.com/articles/nbt.3560">genetic change</a> found in naturally hornless cattle. This is important as many dairy cattle have horns, resulting in the painful practice of <a href="https://www.sciencedirect.com/science/article/abs/pii/S1090023304000486">dehorning</a> calves to reduce the risk of injury to the animal and the farmer.</p>
<p>It’s important not to confuse gene editing with genetic modification, which entails transferring a gene from one species to another. This distinction is necessary for regulatory purposes, especially as the older genetic modification technology has faced <a href="https://www.sciencedirect.com/science/article/abs/pii/S0956713522003863?via%3Dihub">stringent regulations</a> in many countries, hampering its development.</p>
<p>To produce the gene-edited chickens in our study, we used the powerful molecular scissors known as <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4975809/#:%7E:text=Go%20to%3A-,Overview%20of%20CRISPR%2FCas9,genome%20(see%20figure%201).">CRISPR/Cas9</a> to make a single gene edit. We targeted the <a href="https://www.ncbi.nlm.nih.gov/gene/8125">ANP32A</a> protein in chickens. </p>
<p>Compared to normal chickens hatched simultaneously, these gene-edited chickens reached maturity without any discernible adverse consequences on their health and wellbeing.</p>
<p>To test their resistance, we exposed the gene-edited chickens to a low dose of the bird flu virus. Remarkably, 9 out of 10 of these birds displayed complete resistance, and no transmission occurred to other chickens. </p>
<p>Taking a more ambitious step, we inoculated the gene-edited chickens
with a high, unnatural dose of the virus – 1,000 times the low dose. This time, 5 out of the 10 inoculated gene-edited chickens became infected. </p>
<p>We also found that the bird flu virus was capable of adapting to use the edited ANP32A protein, as well as two related proteins – <a href="https://www.ncbi.nlm.nih.gov/gene/10541">ANP32B</a> and <a href="https://www.ncbi.nlm.nih.gov/gene/81611">ANP32E</a>. But we demonstrated through experiments in cells that simultaneously editing all three proteins could completely suppress the virus. </p>
<h2>What’s next?</h2>
<p>Ongoing research aims to identify the specific combination of gene edits needed to create the next generation of gene-edited chickens, providing complete and permanent protection against bird flu.</p>
<p>Gene editing should be regarded as an essential tool for preventing and controlling deadly animal diseases. </p>
<p><a href="https://www.nature.com/articles/s41538-019-0035-y">Supportive government regulations</a> will be required to promote the development of gene editing aimed at enhancing animal health and welfare. </p>
<p>The potential for disease resistant animals to protect global food security and public health is a compelling reason to pursue this innovative path in biotechnology.</p><img src="https://counter.theconversation.com/content/216649/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Alewo Idoko-Akoh was supported in the highlighted study by funding from the UK Research & Innovation's BBSRC </span></em></p>The three flu pandemics of the 20th century originated from birds, making it critical to fight bird flu. Breakthroughs in gene-editing chickens show promise for eliminating the disease in the future.Alewo Idoko-Akoh, Research associate, University of BristolLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2082762023-07-13T12:37:38Z2023-07-13T12:37:38ZPromising assisted reproductive technologies come with ethical, legal and social challenges – a developmental biologist and a bioethicist discuss IVF, abortion and the mice with two dads<figure><img src="https://images.theconversation.com/files/534595/original/file-20230628-23-se3fkd.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2000%2C1500&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A few days after successful fertilization, an embryo becomes a rapidly dividing ball of cells called a blastocyst.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/blastocyst-embryo-illustration-royalty-free-illustration/1498384521">Juan Gaertner/Science Photo Library via Getty Images</a></span></figcaption></figure><p><em>Assisted reproductive technologies are medical procedures that help people experiencing difficulty having or an inability to have biological children of their own. From in vitro fertilization to genetic screening to creation of viable eggs from the <a href="https://doi.org/10.1038/s41586-023-05834-x">skin cells of two male mice</a>, each new development speaks to the potential of reproductive technologies to expand access to the experience of pregnancy.</em> </p>
<p><em>Translating advances from the lab to the clinic, however, comes with challenges that go far beyond the purely technical.</em></p>
<p><em>Conversations around the ethics and implications of cutting-edge research often happen after the fact, when the science and technology have advanced beyond the point at which open dialogue could best protect affected groups. In the spirit of starting such cross-discipline conversations earlier, we invited developmental biologist <a href="https://scholar.google.com/citations?user=i6SghEMAAAAJ&hl=en">Keith Latham</a> of Michigan State University and bioethicist <a href="https://www.researchgate.net/profile/Mary-Faith-Marshall">Mary Faith Marshall</a> of the University of Virginia to discuss the ethical and technological potential of <a href="https://www.npr.org/sections/health-shots/2023/05/27/1177191913/sperm-or-egg-in-lab-breakthrough-in-reproduction-designer-babies-ivg">in vitro gametogenesis</a> and assisted reproductive technology post-Roe.</em></p>
<h2>How new are the ethical considerations raised by assisted reproductive technologies?</h2>
<p><strong>Keith</strong></p>
<p>Every new technology raises many of the same questions, and likely new ones. On the safety and risk-benefit side of the ethical conversation, there’s nothing here that we haven’t dealt with since the 1970s with other reproductive technologies. But it’s important to keep asking questions, because the benefits are hugely dependent on the success rate. There are potential biological costs, but also possible social costs, financial costs, societal costs and many others.</p>
<p><strong>Mary Faith</strong> </p>
<p>It’s probably been that way even longer. One of my mentors, Joseph Francis Fletcher, a pioneering bioethicist and Episcopal priest, wrote a book called “<a href="https://press.princeton.edu/books/hardcover/9780691635224/morals-and-medicine">Morals and Medicine</a>” in 1954. It was the first non-Roman Catholic treatment of bioethics. And he raised a lot of these issues there, including the <a href="https://theconversation.com/jurassic-world-scientists-still-havent-learned-that-just-because-you-can-doesnt-mean-you-should-real-world-genetic-engineers-can-learn-from-the-cautionary-tale-184369">technological imperative</a> – the idea that because we can develop the technology to do something, we therefore should develop it.</p>
<p>Fletcher also said that the use of artifice, or human-made creations, is supremely human. That’s what we do: We figure out how things work and we develop new technologies like vaccines and heart-lung machines based on evolving scientific knowledge.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/534596/original/file-20230628-30-nfjlun.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Microscopy image of mouse ovum being fertilized by mouse sperm" src="https://images.theconversation.com/files/534596/original/file-20230628-30-nfjlun.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/534596/original/file-20230628-30-nfjlun.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=388&fit=crop&dpr=1 600w, https://images.theconversation.com/files/534596/original/file-20230628-30-nfjlun.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=388&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/534596/original/file-20230628-30-nfjlun.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=388&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/534596/original/file-20230628-30-nfjlun.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=487&fit=crop&dpr=1 754w, https://images.theconversation.com/files/534596/original/file-20230628-30-nfjlun.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=487&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/534596/original/file-20230628-30-nfjlun.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=487&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Scientists were able to create a mouse egg from the skin cells of male mice.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/fertilization-of-mouse-ovum-royalty-free-image/523741410">Clouds Hill Imaging Ltd./Corbis Documentary via Getty Images</a></span>
</figcaption>
</figure>
<p>I think that in most cases, scientists should be involved in thinking about the implications of their work. But often, researchers focus more on the direct applications of their work than the potential indirect consequences. </p>
<p>Given the evolution of assisted reproductive technology, and the fact that its evolution is going to continue, I think one of the central questions to consider is, what are the goals of developing it? For assisted reproduction, it’s to help infertile people and people in nontraditional relationships have children.</p>
<h2>What are some recent developments in the field of assisted reproductive technology?</h2>
<p><strong>Keith</strong></p>
<p>One recent advance in assisted reproductive technology is the expansion of <a href="https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2020/03/preimplantation-genetic-testing">pre-implantation genetic testing</a> methods, particularly DNA sequencing. Many genes come in different variants, or alleles, that can be inherited from each parent. Providers can determine whether an embryo bears a “bad” allele that may increase the risk of certain diseases and select embryos with “healthy” alleles.</p>
<p>Genetic screening <a href="https://doi.org/10.1016/j.fertnstert.2022.03.017">raises several ethical concerns</a>. For example, the parents’ genetic profiles could be unwillingly inferred from that of the embryo. This possibility may deter prospective parents from having children, and such knowledge may also have potential effects on any future child. The cost of screening and potential need for additional cycles of IVF may also increase disparities.</p>
<p>There are also considerations about the <a href="https://doi.org/10.1016/j.fertnstert.2022.03.019">accuracy of screening predictions</a> without accounting for environmental effects, and what <a href="https://doi.org/10.1007/s12687-021-00573-w">level of genetic risk</a> is “serious” enough for an embryo to be excluded. More extensive screening also raises concerns about possible misuse for purposes other than disease prevention, such as production of “<a href="https://theconversation.com/an-american-company-will-test-your-embryos-for-genetic-defects-but-designer-babies-arent-here-just-yet-126833">designer babies</a>.”</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/uhb5gd5B-7g?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">In vitro gametogenesis involves making egg or sperm cells from other adult cells in the body.</span></figcaption>
</figure>
<p>At a <a href="https://www.nationalacademies.org/news/2023/02/agenda-for-third-international-summit-on-human-genome-editing-march-6-8">genome-editing conference</a> in March 2023, researchers announced that they were able to <a href="https://doi.org/10.1038/s41586-023-05834-x">delete and duplicate whole chromosomes</a> from the skin cells of male mice to make eggs. This method is one potential way to make eggs that do not carry genetic abnormalities. </p>
<p>They were very upfront that this was done at 1% efficiency in mice, which could be lower in humans. That means something bad happened to 99% of the embryos. The biological world is not typically binary, so a portion of that surviving 1% could still be abnormal. Just because the mice survived doesn’t mean they’re OK. I would say at this point, it would be unethical to try this on people.</p>
<p>As with some forms of genetic screening, using this technique to reduce the risk of one disease could inadvertently increase the risk of another. Determining that it is absolutely safe to duplicate a chromosome would require knowing every allele of every gene on that chromosome, and what each allele could do to the health of a person. That’s a pretty tall order, as that could involve identifying hundreds to thousands of genes, and the effects of all their variants may not be known. </p>
<p><strong>Mary Faith</strong></p>
<p>That raises the issue of efficacy and costs to yet another order of magnitude.</p>
<p><strong>Keith</strong> </p>
<p>Genome editing with <a href="https://theconversation.com/human-genome-editing-offers-tantalizing-possibilities-but-without-clear-guidelines-many-ethical-questions-still-remain-200983">CRISPR technology</a> in people carries similar concerns. Because of potential limitations in how precise the technology can be, it may be difficult for researchers to say they are absolutely 100% certain there won’t be off-target changes in the genome. Proceeding without that full knowledge could be risky. </p>
<p>But that’s where bioethicists need to come into play. Researchers don’t know what the full risk is, so how do you make that risk-benefit calculation?</p>
<p><strong>Mary Faith</strong></p>
<p>There’s the option of a voluntary global moratorium on using these technologies on human embryos. But somebody somewhere is <a href="https://theconversation.com/did-he-jiankui-make-people-better-documentary-spurs-a-new-look-at-the-case-of-the-first-gene-edited-babies-196714">still going to do it</a>, because the technology is just sitting there, waiting to be moved forward.</p>
<h2>How will the legal landscape affect the development and implementation of assisted reproductive technologies?</h2>
<p><strong>Mary Faith</strong></p>
<p>Any research that involves human embryos is in some ways politicized. Not only because the <a href="https://doi.org/10.1038/d41586-020-00127-z">government provides funding</a> to the basic science labs that conduct this research, but because of the wide array of beliefs that members of the public at large have about <a href="https://theconversation.com/defining-when-human-life-begins-is-not-a-question-science-can-answer-its-a-question-of-politics-and-ethical-values-165514">when life begins</a> or <a href="https://theconversation.com/what-is-personhood-the-ethics-question-that-needs-a-closer-look-in-abortion-debates-182745">what personhood means</a>.</p>
<p>The <a href="https://theconversation.com/roe-overturned-what-you-need-to-know-about-the-supreme-court-abortion-decision-184692">Dobbs decision</a>, which overturned the constitutional right to an abortion, has implications for assisted reproduction and beyond. Most people who are pregnant don’t even know they’re pregnant at the earliest stages, and somewhere around <a href="https://theconversation.com/most-human-embryos-naturally-die-after-conception-restrictive-abortion-laws-fail-to-take-this-embryo-loss-into-account-187904">60% of those pregnancies end naturally</a> because of genetic aberrations. Between 1973 and 2005, <a href="https://doi.org/10.1215/03616878-1966324">over 400 women were arrested for miscarriage in the U.S.</a>, and I think that number is going to grow. The implications for reproductive health care, and for assisted reproduction in the future, are challenging and frightening.</p>
<p>What will abortion restrictions mean for people who have <a href="https://www.cdc.gov/art/key-findings/multiple-births.html">multiple-gestation pregnancies</a>, in which they carry more than one embryo at the same time? In order to have one healthy child born from that process, the other embryos often need to be removed so they don’t all die. In the past 40 years, the number of twin births doubled and triplet and higher-order births quadrupled, primarily because of fertility treatments. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/534477/original/file-20230628-27-v0r0uc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Needle touching eggs in petri dish under microscope in IVF" src="https://images.theconversation.com/files/534477/original/file-20230628-27-v0r0uc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/534477/original/file-20230628-27-v0r0uc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/534477/original/file-20230628-27-v0r0uc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/534477/original/file-20230628-27-v0r0uc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/534477/original/file-20230628-27-v0r0uc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/534477/original/file-20230628-27-v0r0uc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/534477/original/file-20230628-27-v0r0uc.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">IVF may involve transferring more than one embryo at a time.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/in-vitro-fertilization-royalty-free-image/1272954210">Antonio Marquez lanza/Moment via Getty Images</a></span>
</figcaption>
</figure>
<p><strong>Keith</strong> </p>
<p>IVF may transfer one, two, or sometimes three embryos at a time. The <a href="https://doi.org/10.1016/j.jpeds.2022.11.038">cost of care for preterm birth</a>, which is one possible outcome of multiple-gestation pregnancies, can be high. That’s in addition to the <a href="https://doi.org/10.1016/j.ajog.2013.10.005">cost of delivery</a>. IVF clinics are increasingly transferring just one embryo to mitigate such concerns.</p>
<p>The life-at-conception bills that have been put forth in some U.S. state legislatures and Congress may contain language claiming they are not meant to prevent IVF. But the language of the bills could be extended to affect procedures such as IVF with pre-implantation genetic testing to detect chromosomal abnormalities, particularly when single-embryo transfer is the goal. Pre-implantation genetic testing has been increasing, with one study estimating that <a href="https://doi.org/10.1001/jama.2022.1892">over 40% of all IVF cycles</a> in the U.S. in 2018 involved genetic screening. </p>
<p>Could life-at-conception bills criminalize clinics that don’t transfer embryos known to be genetically abnormal? Freezing genetically abnormal embryos could avoid destroying them, but that raises questions of, to what end? Who would pay for the storage, and who would be responsible for those embryos?</p>
<h2>How can we determine whether the risks outweigh the benefits when so much is unknown?</h2>
<p><strong>Keith</strong></p>
<p>Conducting studies in animal models is an important first step. In some cases, it either hasn’t been done or hasn’t been done extensively. Even with animal studies, you have to recognize that mice, rabbits and monkeys are not human. Animal models may reduce some risks before a technology is used in people, but they won’t eliminate all risks, because of biological differences between species.</p>
<p><strong>Mary Faith</strong> </p>
<p>We could look to the example of <a href="https://www.genome.gov/25520302/online-education-kit-1972-first-recombinant-dna">early recombinant DNA research in the U.S.</a> The federal government created the <a href="https://doi.org/10.1089%2Fhum.2013.2524">Recombinant DNA Advisory Committee at the National Institutes of Health</a> to oversee animal and early-phase human research involving synthetic or hybrid genetic material. </p>
<p>The <a href="https://doi.org/10.1126/science.307.5712.1028b">death of Jesse Gelsinger</a>, who was a participant in a gene therapy clinical trial in 1999, led to a halt in all gene therapy clinical trials in the U.S. for a time. When the Food and Drug Administration investigated what went wrong, they found huge numbers of adverse events in both humans and animals that should have been reported to the advisory committee but weren’t. Notably, the principal investigator of the trial was also the <a href="https://sciencehistory.org/stories/magazine/the-death-of-jesse-gelsinger-20-years-later/">primary shareholder</a> of the biotech company that made the drug being tested. That raises questions about the reality of oversight.</p>
<p>I think something like that earlier NIH advisory committee but for reproductive technologies would still be advisable. But researchers, policymakers and regulators need to learn from the lessons of the past to try to ensure that – especially in early-phase research – we’re very thoughtful about the potential risks and that research participants really understand what the implications are for participation in research. That would be one model for translating research from the animal into the human.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/534481/original/file-20230628-30590-2nwhy8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Child looking into a slip lamp microscope for an eye exam with a doctor" src="https://images.theconversation.com/files/534481/original/file-20230628-30590-2nwhy8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/534481/original/file-20230628-30590-2nwhy8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/534481/original/file-20230628-30590-2nwhy8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/534481/original/file-20230628-30590-2nwhy8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/534481/original/file-20230628-30590-2nwhy8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/534481/original/file-20230628-30590-2nwhy8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/534481/original/file-20230628-30590-2nwhy8.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 FDA approved a gene therapy for a form of congenital vision loss in 2017. The child in this photo, then 8, first received gene therapy at age 4.</span>
<span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/BlindnessTreatmentPrice/c567cc3a2b244cac8afc2b5ae2c62ca3">Bill West/AP Photo</a></span>
</figcaption>
</figure>
<p><strong>Keith</strong></p>
<p>A process to make sure that the people conducting studies don’t have a conflict of interest, like having the potential to commercially profit from the technology, would be useful. </p>
<p>Caution, consensus and cooperation should not take second place to profit motives. Altering the human genome in a way that allows human-made genetic changes to be <a href="https://doi.org/10.1089/crispr.2020.0096">propagated throughout the population</a> has a potential to alter the genetics of the human species as a whole. </p>
<p><strong>Mary Faith</strong></p>
<p>That raises the question of how long it will take for long-term effects to show. It’s one thing for an implanted egg not to survive. But how long will it take to know whether there are effects that aren’t obvious at birth?</p>
<p><strong>Keith</strong> </p>
<p>We’re still collecting long-term outcome data for people born using different reproductive technologies. So far there have been no obviously horrible consequences. But some abnormalities could take decades to manifest, and there are many variables to contend with. </p>
<p>One can arguably say that there’s substantial good in helping couples have babies. There can be a benefit to their emotional well-being, and reproduction is a natural part of human health and biology. And a lot of really smart, dedicated people are putting a lot of energy into making sure that the risks are minimized. We can also look to some of the practices and approaches to oversight that have been used over the past several decades.</p>
<p><strong>Mary Faith</strong></p>
<p>And thinking about international guidelines, such as from the <a href="https://cioms.ch">Council for International Medical Science</a> and other groups, could provide guidance on protecting human research subjects.</p>
<p><strong>Keith</strong></p>
<p>You hate to advocate for a world where the automatic response to anything new is “no, don’t do that.” My response is, “Show me it’s safe before you do it.” I don’t think that’s unreasonable.</p>
<p>Some people have a view that scientists don’t think about the ethics of research and what’s right and wrong, advisable or inadvisable. But we do think about it. I co-direct a research training program that includes teaching scientists how to responsibly and ethically conduct research, including speakers who specifically address the ethics of reproductive technologies. It is valuable to have a dialogue between scientists and ethicists, because ethicists will often think about things from a different perspective. </p>
<p>As people go through their scientific careers and see new technologies unfold over time, these discussions can help them develop a deeper appreciation and understanding of the broader impact of their research. It becomes our job to make sure that each generation of scientists is motivated to think about these things. </p>
<p><strong>Mary Faith</strong></p>
<p>It’s also really important to include stakeholders – people who are nonscientists, people who experience barriers to reproduction and people who are opposed to the idea – so they have a voice at the table as well. That’s how you get good policies, right? You have everyone who should be at the table, at the table.</p><img src="https://counter.theconversation.com/content/208276/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Scientists can create viable eggs from two male mice. In the wake of CRISPR controversies and restrictive abortion laws, two experts start a dialogue on ethical research in reproductive biology.Keith Latham, Professor of Animal Science, Adjunct Professor of Obstetrics, Gynecology and Reproductive Biology, Michigan State UniversityMary Faith Marshall, Professor of Biomedical Ethics, University of VirginiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2008032023-04-19T12:47:07Z2023-04-19T12:47:07ZErasing or replacing errors in a patient’s genetic code can treat and cure some genetic diseases<figure><img src="https://images.theconversation.com/files/512982/original/file-20230301-20-1v7gbc.jpg?ixlib=rb-1.1.0&rect=187%2C123%2C1762%2C1212&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Gene editing may hold promise for curing some diseases.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/concept-of-treatment-and-adjustment-of-dna-royalty-free-image/1316503044?phrase=gene%20editing&adppopup=true">Natali_Mis/iStock via Getty Images Plus</a></span></figcaption></figure><p><em>Genetic diseases can have devastating consequences for the people who inherit them. In recent years, scientists have found that there are human genetic diseases that might be treatable, and perhaps even curable, through gene editing. Gene editing is the process by which sections of a person’s DNA are altered. Commonly compared to a word processor or a pencil and eraser, precision gene editing agents can alter sections of a person’s genome to correct “misspellings,” or mutations, in their DNA.</em> </p>
<p><em><a href="https://chemistry.harvard.edu/people/david-r-liu">David Liu</a> is a professor of natural sciences at Harvard University. He co-founded several biotechnology companies including Prime Medicine, Beam Therapeutics, Editas Medicine, Chroma Medicine, Pairwise Plants, Exo Therapeutics, Resonance Medicine, and Nvelop Therapeutics. Liu and his team pioneered <a href="https://doi.org/10.1038/nature17946">base</a> editing and <a href="https://doi.org/10.1038/s41586-019-1711-4">prime</a> editing, two new innovative methods of gene editing that allow for precise alterations to a person’s genetic code.</em></p>
<p><em>In March, Liu’s video was shared with participants at the 2023 <a href="https://www.imaginesolutionsconference.com/">Imagine Solutions Conference</a> in Naples, Florida, about how gene editing works, why it is important, and the strides he and his team have made in the field so far.</em> </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/0XLdz4e_ML4?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">David Liu speaking at the Imagine Solutions 2023 Conference.</span></figcaption>
</figure>
<p><strong>What is gene editing, and why are scientists interested in developing and using this tool?</strong></p>
<p><a href="https://www.genome.gov/about-genomics/policy-issues/what-is-Genome-Editing">Gene editing</a> is a technique that makes it possible to purposefully change genes in the <a href="https://medlineplus.gov/genetics/understanding/basics/dna/">DNA</a> of different organisms, including <a href="https://doi.org/10.3390/ijms21165665">crops</a> and <a href="https://doi.org/10.1080/19768354.2020.1726462">animals</a>. Scientists are interested in developing and using genome editors because they are powerful tools for studying biology, treating human diseases and <a href="https://doi.org/10.3389/fsufs.2021.685801">improving agriculture</a>. More than <a href="https://clinicaltrials.gov">50 clinical trials</a> using gene editing to treat a variety of disorders are in progress.</p>
<p>According to the U.S. <a href="https://www.genome.gov/dna-day/15-ways/rare-genetic-diseases">National Human Genome Research Institute</a>, around 280 million individuals worldwide live with a rare genetic disease. Most of these individuals have few to no treatment options, leaving them resigned to their genetic fate.</p>
<p><strong>Can you explain the difference between base and prime editing? Why would scientists use one over the other?</strong></p>
<p>Neither <a href="https://doi.org/10.1038/s41573-020-0084-6">base editors</a> nor <a href="https://doi.org/10.1038/s41434-021-00263-9">prime editors</a> exist in nature; instead, both were engineered in our laboratory from natural and laboratory-evolved components. </p>
<p><a href="https://doi.org/10.1038/nature17946">Base editing</a>, often compared to a pencil and eraser, can precisely and efficiently correct <a href="https://doi.org/10.1038/nature24644">four of the most common types of misspellings</a> that occur in DNA, together accounting for about 30% of all known disease-causing DNA errors. Base editors perform a chemical reaction on an individual DNA letter, or “base,” rearranging its atoms to instead become a different DNA base. But base editing cannot be used to correct mistakes such as extra letters, missing letters or the remaining types of single-letter misspellings in DNA. </p>
<p>In contrast, <a href="https://doi.org/10.1038/s41586-019-1711-4">prime editors</a>, sometimes compared to the “search and replace” feature in a word processor, can replace any stretch of up to hundreds of DNA letters with virtually any other sequence of letters. In theory, the versatility of prime editing makes it possible to correct most known DNA misspellings that cause disease by restoring the typical DNA sequence. </p>
<p>Base editing and prime editing each have their own strengths and weaknesses. Whether a scientist should use base or prime editing depends on numerous factors such as the specific sequence being edited, its unique sequence context, whether the edit will be made inside an animal or patient, and the specific goals of the scientist. </p>
<p><strong>How can gene editing treat disease?</strong></p>
<p>The words “bean” and “been” differ by only a single letter, yet they have completely different meanings. In a cellular context, a single-letter misspelling in a specific position in a person’s DNA – for example, from a C to a T – can mean the difference between a healthy individual and an individual with progeria, a rare genetic disease that causes children to age rapidly. Base editing has the potential to correct these small but critical DNA misspellings to reverse or cure disease.</p>
<p><a href="https://doi.org/10.1038/s41586-020-03086-7">In a 2021 study</a> that our lab conducted in collaboration with scientists at the National Institutes of Health and Vanderbilt University, we used base editing to reverse progeria in mice and more than doubled their life span. In the same year, we used base editing to convert a diseased form of the hemoglobin gene <em>HBB</em> to a benign variant to <a href="https://doi.org/10.1038/s41586-021-03609-w">treat sickle-cell disease in mice</a>. </p>
<p>Base editing has also been successfully used in humans. After treatments of chemotherapy and a bone marrow transplant failed to treat 13-year-old <a href="https://www.bbc.com/news/health-63859184">Alyssa’s</a> pediatric leukemia, she enrolled in a <a href="https://www.isrctn.com/ISRCTN15323014">clinical trial</a> led by <a href="https://www.waseemqasim.com/">Waseem Qasim’s team</a> at the University of College London. The base-edited T-cells cleared Alyssa’s cancer and she remains in complete remission seven months later. </p>
<p><strong>What implications does prime editing have for the study and treatment of genetic disease and human health?</strong></p>
<p>Much like base editing, <a href="https://doi.org/10.1016/j.tcb.2020.01.004">prime editing</a> has tremendous implications for studying and treating genetic diseases. Because of its unique ability to make virtually any localized change in DNA at a target sequence, prime editing has the potential to correct a much larger number of mutations that are known to cause genetic diseases than was previously possible. Before prime editors can be used routinely to treat genetic diseases, however, they must be tested for their safety and efficacy in patients, and for their compatibility with different delivery platforms.</p>
<p>Additionally, the therapeutic application of any genome editing technology requires a clear understanding of the relationship between the genetic mutation and the resulting disease to ensure that the benefits outweigh the risks. </p>
<p><strong>What recent or ongoing development are you most excited about in your field?</strong></p>
<p>I am excited that many labs, including <a href="https://www.liugroup.us/">my own</a>, are <a href="https://doi.org/10.1126/science.aax9181">developing methods</a> <a href="https://doi.org/10.1038/s41587-021-01133-w">to precisely</a> <a href="https://doi.org/10.1038/s41587-021-01133-w">install</a> entire healthy genes into specific positions in the human genome. This could expand the potential therapeutic reach of gene editing. </p>
<p>I’m also excited about <a href="https://doi.org/10.1038/s41392-019-0089-y">ongoing efforts</a> to develop delivery technologies that can safely and efficiently deliver genome editing agents into target cells in animals and human patients. Genome editing agents are unable to easily enter cells because of their large size, unlike <a href="https://www.cancer.gov/publications/dictionaries/cancer-terms/def/small-molecule-drug">small-molecule drugs</a> like ibuprofen and aspirin which can easily enter cells due to their low molecular weight. As a result, scientists have to use creative ways to deliver genome editors to their targets — a critical step if we hope to broaden the scope of therapeutic gene editing.</p>
<p>To this end, we recently developed <a href="https://doi.org/10.1016/j.cell.2021.12.021">engineered viruslike particles</a>, which are capable of delivering base editors and prime editors into specific tissues in living organisms. As the field continues to develop and improve delivery methods, the promise of therapeutic genome editing will continue to include more patient communities.</p>
<p><strong>What ethical aspects of this technology have you and other researchers considered?</strong></p>
<p>There are several ethical issues surrounding the technology that researchers in the field <a href="https://www.nature.com/articles/d41586-019-00726-5">have considered</a>, including the challenges of <a href="https://doi.org/10.1038/s41587-021-01191-0">achieving equitable access</a> to genome editing technologies, the <a href="https://doi.org/10.1089/crispr.2021.0053">potential for increased stigmatization</a> of marginalized individuals and the <a href="https://doi.org/10.1007/s13238-017-0477-4">potential for misuse</a>. In cases where the technology is used with good intent, such as to treat disease and alleviate suffering, questions of <a href="https://doi.org/10.1016/j.ymthe.2016.12.012">patient accessibility</a> become paramount.</p>
<p>No fundamental technology is inherently good or bad, and the ability to edit our genomes is no exception. My hope continues to be that we collectively and thoughtfully choose to use these powerful technologies for the betterment of as many people as possible.</p><img src="https://counter.theconversation.com/content/200803/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>DRL is a co-founder and consultant for Beam Therapeutics, Prime Medicine, Pairwise Plants, Exo Therapeutics, Chroma Medicine, Resonance Medicine, and Nvelop Therapeutics. He owns founders’ equity in these companies, receives consultancies from them, and serves on their scientific advisory boards. He also serves as a scientific advisory board member and equity owner of Tevard Biosciences and Insitro. DRL may receive honoraria and travel reimbursements for some speaking engagements. He is a co-inventor on patents related to his research, as listed on his CV at <a href="http://liugroup.us">http://liugroup.us</a>. Some of these patents have been licensed to companies including those listed above. Potential conflicts of interest between his academic activities and his activities with other entities including the companies above are actively disclosed and managed in accordance with the conflict of interest policies of the Broad Institute, Harvard University, and HHMI.
The policies are available at:
<a href="https://www.broadinstitute.org/administration/conflict-interest-policy">https://www.broadinstitute.org/administration/conflict-interest-policy</a>
<a href="https://vpr.harvard.edu/pages/financial-conflict-interest-policy">https://vpr.harvard.edu/pages/financial-conflict-interest-policy</a>
<a href="https://www.hhmi.org/about/policies">https://www.hhmi.org/about/policies</a></span></em></p>Chemist David Liu explains how gene editing is paving the way to treating and even curing certain genetic diseases.David Liu, Professor of the Natural Sciences at Harvard University, Harvard UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1990252023-02-14T14:03:54Z2023-02-14T14:03:54ZWhat is gene editing and how could it shape our future?<figure><img src="https://images.theconversation.com/files/508343/original/file-20230206-15-fnxjey.jpg?ixlib=rb-1.1.0&rect=14%2C7%2C4977%2C2275&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Gene editing revolutionised science.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/abstract-luminous-dna-molecule-genetic-gene-1395147224">PopTika/Shutterstock</a></span></figcaption></figure><p>It is the most exciting time in genetics <a href="https://www.google.com/search?q=when+was+dna+discovered&rlz=1C1VDKB_en-GBGB1004GB1004&oq=when+was+dna+&aqs=chrome.1.69i57j0i512l7j0i131i433i512j0i512.4702j0j7&sourceid=chrome&ie=UTF-8">since the discovery of DNA in 1953</a>. This is mainly due to scientific breakthroughs including the ability to change DNA through a process called gene editing. </p>
<p>The potential for this technology is astonishing – from treating genetic diseases, <a href="https://www.nature.com/articles/s41588-022-01046-7">modifying food crops</a> to withstanding pesticides or changes in our climate, or even to <a href="https://www.theguardian.com/science/2023/jan/31/gene-editing-company-hopes-to-bring-dodo-back-to-life">bring the dodo “back to life”</a>, as one company claims it hopes to do.</p>
<p>We will only be hearing more about gene editing in the future. So if you want to make sure you understand new updates, you first need to get to grips with what gene editing actually is. </p>
<p>Our DNA is made of four key <a href="https://www.cancer.gov/publications/dictionaries/genetics-dictionary/def/base-pair">molecules called bases (A, T, C and G)</a>. Sequences of these four bases are grouped into genes. These genes act as the “code” for key substances the body should make, such as proteins. Proteins are important molecules, vital for maintaining a healthy and functional human being. </p>
<p>Genes can be short, typically made of less than a hundred bases. A good example includes <a href="https://www.frontiersin.org/articles/10.3389/fgene.2021.559998/full">ribosomal genes</a>, which code for different ribosomes, molecules which help create new proteins. </p>
<p>Long genes are made up of millions of bases. For example, the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4767260/#:%7E:text=The%20dystrophin%20gene%20is%20the,spanning%20one%20or%20multiple%20exons.">DMD gene</a> codes for a protein called dystrophin, which supports the structure and strength of muscle cells. DMD has over 2.2 million bases.</p>
<h2>How does gene editing work?</h2>
<p>Gene editing is a technology that can change DNA sequences at one or more points in the strand. Scientists can remove or change a single base or insert a new gene altogether. Gene editing can literally rewrite DNA. </p>
<p>There are different ways to edit genes, but the most popular technique uses a technology called CRISPR-Cas9, first documented in a <a href="https://www.science.org/doi/10.1126/science.1225829">pioneering paper</a> published in 2012. <a href="https://www.nature.com/articles/522020a">Cas9</a> is an enzyme that acts like a pair of scissors that can cut DNA. </p>
<p>It is assisted by a strand of RNA (a molecule similar to DNA, in this case created by the scientist), which guides the Cas9 enzyme to the part of the DNA that the scientist wants to change and binds it to the target gene. </p>
<p>Depending upon what the scientist wants to achieve, they can just remove a segment of the DNA, introduce a single base change (for example changing an A to a G), or insert a larger sequence (such as a new gene). Once the scientist is finished, the natural DNA repair processes take over and glue the cuts back together. </p>
<h2>What could gene editing do?</h2>
<p>The benefits of gene editing to humanity could be significant. For example, making a single base change in people’s DNA could be a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266759/">future treatment</a> for sickle cell disease, a genetic blood disease. People with this disease have just one base that has mutated (from A to T). This makes the gene easier to edit compared with more complex genetic conditions such as heart disease or schizophrenia. </p>
<p>Scientists are also developing new techniques to insert larger segments of bases into the DNA of crops in the hope they can create <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8808358/#:%7E:text=The%20transgenic%20CRISPR%20lines%20exhibited,control%20of%20drought%2Dresponsive%20genes">drought resilient crops</a> and help us adapt to climate change. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/2pp17E4E-O8?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
</figure>
<h2>Why is gene editing controversial?</h2>
<p>Gene editing is a controversial topic. Unless governments work together with scientists to regulate its use, it could become another technology that benefits only the wealthiest people. </p>
<p>And it comes with risk. </p>
<p>The first case of illegal implantation of a genetically edited embryo was reported in 2019 in China, and led to <a href="https://www.theguardian.com/world/2019/dec/30/gene-editing-chinese-scientist-he-jiankui-jailed-three-years">the imprisonment of three scientists</a>. The scientists had attempted to protect twin fetuses from HIV being passed on by their father. </p>
<p>But when other scientists read passages from an unpublished paper written by the DNA experiment lead about the twins, they
<a href="https://www.theguardian.com/science/2019/dec/04/china-gene-edited-baby-experiment-may-have-created-unintended-mutations">feared that instead of introducing immunity</a>, the researchers probably created mutations whose consequences are still unknown. </p>
<p>The risks of developing designer babies are so high it is unlikely that it will become legal anytime soon. A tiny mistake could destroy the health of a baby or lead to other diseases throughout their lifetime, such as increased risk of cancer.</p>
<p>Laws and regulations surrounding this technology are strict. Most countries prohibit the implantation of a human embryo that has been genetically altered in any way. However, as the 2019 example shows, laws can be broken. </p>
<p>Gene editing has its advantages. It holds the potential to cure genetic disease and create crops resistant to drought. But scientists need to work closely with law and policy makers to ensure the technology can be used for the benefit of mankind while minimising the risks. </p>
<p>The fact a private company recently announced plans to try to bring back the dodo shows how important it is that international gene-editing laws keep up with the ambitions of corporations.</p><img src="https://counter.theconversation.com/content/199025/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gavin Bowen-Metcalf 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>Gene editing promises everything from treatments for serious conditions like sickle cell disease to the resurrection of the dodo.Gavin Bowen-Metcalf, Lecturer in Biomedical Sciences, Anglia Ruskin UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1967142022-12-20T17:52:36Z2022-12-20T17:52:36ZDid He Jiankui ‘Make People Better’? Documentary spurs a new look at the case of the first gene-edited babies<figure><img src="https://images.theconversation.com/files/501995/original/file-20221219-14-6lxobo.jpg?ixlib=rb-1.1.0&rect=218%2C11%2C2914%2C2144&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">He Jiankui seemed unprepared for the furor set off by his bombshell announcement.</span> <span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:He_Jiankui.jpg">The He Lab/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>In the four years since an experiment by disgraced scientist He Jiankui resulted in the <a href="https://apnews.com/article/ap-top-news-international-news-ca-state-wire-genetic-frontiers-health-4997bb7aa36c45449b488e19ac83e86d">birth of the first babies with edited genes</a>, numerous articles, books and <a href="https://nap.nationalacademies.org/catalog/25665/heritable-human-genome-editing">international</a> <a href="https://www.who.int/groups/expert-advisory-committee-on-developing-global-standards-for-governance-and-oversight-of-human-genome-editing">commissions</a> have reflected on whether and how heritable genome editing – that is, modifying genes that will be passed on to the next generation – should proceed. They’ve reinforced an international consensus that it’s premature to proceed with heritable genome editing. Yet, concern remains that some individuals might buck that consensus and recklessly forge ahead – just as He Jiankui did.</p>
<p>Some observers – <a href="https://scholar.google.com/citations?user=yebS-LIAAAAJ&hl=en&oi=ao">myself included</a> – have <a href="https://theconversation.com/rogue-science-strikes-again-the-case-of-the-first-gene-edited-babies-107684">characterized He as a rogue</a>. However, the new documentary “<a href="https://makepeoplebetterfilm.com/">Make People Better</a>,” directed by filmmaker Cody Sheehy, leans toward a different narrative. In its telling, He was a misguided centerpiece of a broader ecosystem that subtly and implicitly supported rapid advancement in gene editing and reproductive technologies. That same system threw He under the bus – <a href="https://www.technologyreview.com/2019/12/30/131061/he-jiankui-sentenced-to-three-years-in-prison-for-crispr-babies/">and into prison</a> – when it became evident that the global community strongly rejected his experiments.</p>
<h2>Creation of the ‘CRISPR babies’</h2>
<p>“Make People Better” outlines an already well-documented saga, tracing the path of He from a promising young scientist at Rice and Stanford to a driven researcher establishing a laboratory in China that secretly worked to make heritable genome editing a reality.</p>
<p>He’s experiment involved using the <a href="https://theconversation.com/nobel-prize-for-crispr-honors-two-great-scientists-and-leaves-out-many-others-147730">CRISPR-Cas9 technique</a>. Sometimes compared to “molecular scissors,” this precision tool allows scientists to make very specific edits to DNA in living cells. He used CRISPR to alter the CCR5 gene in human embryos with the goal of conferring immunity to HIV. These embryos were brought to term, resulting in the birth of at <a href="https://www.newscientist.com/article/mg25533930-700-whats-next-for-the-gene-edited-children-from-crispr-trial-in-china/">least three children with altered DNA</a>. </p>
<p>The revelation of the births of the first gene-edited babies in November 2018 resulted in an international uproar. A <a href="https://www.theatlantic.com/science/archive/2018/12/15-worrying-things-about-crispr-babies-scandal/577234/">laundry list</a> of ethical failings in He’s experiment <a href="https://www.nature.com/articles/d41586-018-07573-w">quickly became evident</a>. There was insufficient proof that editing embryos with CRISPR was safe enough to be done in humans. Appropriate regulatory approval had <a href="https://www.scmp.com/news/china/science/article/2182964/china-confirms-gene-edited-babies-blames-scientist-he-jiankui">not been obtained</a>. The parents’ consent was <a href="https://link.springer.com/article/10.1007/s11673-019-09953-x">grossly inadequate</a>. And the whole endeavor was <a href="https://apnews.com/article/health-science-china-medical-ethics-ap-top-news-13303d99c4f849829e98350301e334a9">shrouded in secrecy</a>.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/4-u0fXnX4No?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Trailer for the documentary ‘Make People Better.’</span></figcaption>
</figure>
<h2>New context, same story</h2>
<p>Three figures play a central role in “Make People Better”‘s study of He Jiankui. There’s Antonio Regalado, the reporter from MIT Technology Review who broke the original story. There’s Ben Hurlbut, an ethicist and confidante of He. And there’s Ryan (the documentary withholds his full identity), a public relations representative who worked with He to make gene editing palatable to the world. He Jiankui himself was not interviewed, though his voice permeates the documentary in previously unreleased recordings by Hurlbut.</p>
<p>Regalado and Hurlbut have <a href="https://www.technologyreview.com/2019/12/03/75084/nature-jama-rejected-he-jiankui-crispr-baby-lulu-nana-paper/">already</a> <a href="https://doi.org/10.1353/pbm.2020.0013">written</a> a <a href="https://www.technologyreview.com/2019/02/21/137309/the-crispr-twins-had-their-brains-altered/">considerable</a> <a href="https://doi.org/10.1038/d41586-018-07881-1">amount</a> on this saga, so the documentary’s most novel contribution comes from Ryan’s discussion of his public relations work with He. Ryan appears to be a true believer in He’s vision to literally “make people better” by using gene editing to prevent dreadful diseases. </p>
<p>But Ryan is aware that public backlash could torpedo this promising work. His reference point is the initial <a href="https://www.pewresearch.org/science/2015/01/29/public-and-scientists-views-on-science-and-society/">public hostility to GMO foods</a>, and Ryan strove to avoid that outcome by gradually easing the public in to the heritable gene editing experiment.</p>
<p>This strategy turned out to be badly mistaken for a variety of reasons. He Jiankui was himself eager to publicize his work. Meanwhile, Regalado’s <a href="https://www.technologyreview.com/2018/11/25/138962/exclusive-chinese-scientists-are-creating-crispr-babies/">tenacious journalism</a> led him to a clinical trials registry where He had quietly posted about the study.</p>
<p>But ultimately, those factors just affected the timing of revelation. Both Ryan and He failed to appreciate that they had very little ability to influence how the experiment would be received, nor how much condemnation would result.</p>
<h2>Blind spots</h2>
<p>While some documentaries strive to be flies on the wall, objectivity is elusive. Tone, framing, editing and choice of interview subjects all coalesce into a narrative with a perspective on the subject matter. A point of view is not itself objectionable, but it opens the documentary to critiques of its implicit stance.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1599893869348671490"}"></div></p>
<p>An uncomfortable tension lies at the center of “Make People Better.” </p>
<p>On the one hand, the documentary gives substantial attention to Hurlbut and Ryan, who emphasize that He did not act alone. He discussed his plans with <a href="https://doi.org/10.1126/science.365.6452.430">dozens of people</a> in China and around the world, whose implicit support was essential to both the experiment and his confidence that he was doing nothing wrong.</p>
<p>On the other hand, the documentary focuses on understanding He’s background, motives and ultimate fate. Other figures who might have influenced He to take a different path fade into the background – sometimes quite literally, appearing for only seconds before the documentary moves on.</p>
<p>Indeed, as a biomedical ethicist, I believe there is good reason to put responsibility for the debacle squarely on He’s shoulders. Before the news broke in 2018, international panels of experts had already issued <a href="https://www.nationalacademies.org/news/2015/12/on-human-gene-editing-international-summit-statement">advisory statements</a> that heritable gene editing was premature. Individuals like Hurlbut personally advised He as much. The secrecy of the experiment itself is a testament: He must have suspected the international community would reject the experiment if they knew what was going on. </p>
<p>If He had gone through proper, transparent channels – <a href="https://www.cos.io/initiatives/prereg">preregistering the trial</a> and consulting publicly with international experts on his plans before he began – the whole saga could have been averted. He chose a different, more dangerous and secretive path from the vast majority of researchers working in reproductive biotechnology, which I suggest must be acknowledged.</p>
<p>The documentary does not reflect critically on its own title. The origin of the phrase “make people better” is surprising and the film’s most clever narrative moment, so I won’t spoil it. But does heritable gene editing really make people better? <a href="https://doi.org/10.1111/bioe.12878">Perhaps instead</a>, it makes better people. </p>
<p>The gene-edited babies were created via in vitro fertilization specifically as a part of He’s experiment. They would not have existed if He had never gotten involved in gene editing. So, some would argue, He did not save any individual from contracting HIV. Rather, he created new people potentially less likely to contract HIV than the general population. </p>
<p><a href="https://doi.org/10.1007/s11019-020-09947-2">I contend</a> that this doesn’t mean gene editing is pointless. From a population health perspective, gene editing could save lives by reducing the incidence of certain diseases. But this perspective does change the moral tenor of gene editing, perhaps reducing its urgency.</p>
<p>What’s more, editing CCR5 is a dubious means to improve human well-being, since there are already effective ways to prevent HIV infection that are far less risky and uncertain than heritable gene editing. <a href="https://doi.org/10.17226/25665">Scientific consensus suggests</a> that the best first-in-human candidates for heritable gene editing are instead devastating genetic disorders that cannot be ameliorated in other ways.</p>
<h2>The future for He Jiankui</h2>
<p>Perhaps due to the timing of its filming, the documentary does not dwell on He being <a href="https://www.science.org/content/article/chinese-scientist-who-produced-genetically-altered-babies-sentenced-3-years-jail">sentenced to three years in Chinese prison</a> as a result of the experiment, nor mention that <a href="https://www.technologyreview.com/2022/04/04/1048829/he-jiankui-prison-free-crispr-babies/">he was released</a> early in 2022.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1590530211929784320"}"></div></p>
<p>Evidently, He is not content to fade quietly into obscurity. He says he is slated in March 2023 to <a href="https://pandaily.com/chinese-gene-editing-scientist-he-jiankui-sets-up-beijing-lab-following-prison-release/">give a talk at the University of Oxford</a> that may shed more light on his motives and actions. In the meantime, he has <a href="https://www.statnews.com/2022/11/29/after-prison-crispr-babies-scientist-is-attempting-comeback/">established a new biotech start-up</a> focused on developing gene therapies. To be clear, this work does not involve editing embryos.</p>
<p>Still, it appears prison has not diminished He’s ambition. <a href="https://www.scmp.com/news/china/science/article/3201896/chinese-scientist-behind-gene-edited-babies-speak-oxford-university">He claims</a> that he could develop a cure for the degenerative genetic disease Duchenne muscular dystrophy – if he receives funding in excess of US$100 million. </p>
<p>To me, this ambition reflects a curious symmetry between Regalado and He in “Make People Better.” Both are driven to be first, to be at the forefront of their respective fields. Sometimes, as with Regalado, this initiative can be good – his intrepid reporting and instinct to publish quickly brought He’s unethical experiment to a rapid close. But in other cases, like He’s, that drive can lead to dangerous science that runs roughshod over ethics and good governance. </p>
<p>Perhaps, then, the best lesson a viewer can take from “Make People Better” is that ambition is a double-edged sword. In the years to come, it will be up to the international community to keep such ambition in check and ensure proper restrictions and oversight on heritable genome editing.</p><img src="https://counter.theconversation.com/content/196714/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>G. Owen Schaefer does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Scientific and public uproar resulted when the Chinese scientist announced the births of the first human babies with heritable edits to their genes. A new documentary reexamines the saga.G. Owen Schaefer, Assistant Professor in Biomedical Ethics, National University of SingaporeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1941472022-11-28T19:04:00Z2022-11-28T19:04:00ZChasing future biotech solutions to climate change risks delaying action in the present – it may even make things worse<figure><img src="https://images.theconversation.com/files/497508/original/file-20221128-14-c08jwp.jpg?ixlib=rb-1.1.0&rect=0%2C62%2C4601%2C2497&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Getty Images</span></span></figcaption></figure><p>The world is under growing pressure to find sustainable options to cut emissions or lessen the impacts of climate change. </p>
<p>Technology entrepreneurs from around the globe claim to have the solutions – not just yet, but soon. The biotech sector in particular is now using climate change as an urgent argument for <a href="https://www.rnz.co.nz/news/business/465113/medical-biotech-researchers-call-for-more-govt-funds">more government funding</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1083956/">public support</a> and <a href="https://geneticliteracyproject.org/2022/03/29/viewpoint-no-dna-is-not-a-drug-why-the-fdas-continued-insistence-to-regulate-gene-edited-research-animals-as-drugs-blocks-us-based-innovation/">fewer regulatory hurdles</a> for their industry.</p>
<p>But the urgency of climate change creates greater risk of superficial claims and actions. In our new <a href="https://www.sciencedirect.com/science/article/pii/S1877343522000744">research</a>, we describe how the current “technology push” cycle perpetually promises to rescue humanity from climate change, and in doing so, delays real progress.</p>
<p>The pipeline for salvation technology is long and the benefit is hypothetical. Like the character Wimpy from Popeye, technology developers want their hamburger today but will pay back society with climate solutions on some future Tuesday.</p>
<p>Climate change is an existential threat, but it is only one of many symptoms of environmental damage we’ve caused. Humanity has pushed Earth beyond multiple <a href="https://pubs.acs.org/doi/pdf/10.1021/acs.est.1c04158">boundary limits</a> and the accumulation of greenhouse gases in the atmosphere is merely one indicator of the many excesses of human activity.</p>
<p>Technology solutions not only rarely lead to sustainable solutions, they may exacerbate harm. Lulled into complacency by “technological imaginaries”, we wait too long to enact difficult but effective solutions.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-a-new-biotech-rule-will-foster-distrust-with-the-public-and-impede-progress-in-science-139547">How a new biotech rule will foster distrust with the public and impede progress in science</a>
</strong>
</em>
</p>
<hr>
<h2>Tech solutions only address symptoms</h2>
<p>Biotechnologies could make valuable contributions to halting or ameliorating the impacts of climate change. Contributions that reduce greenhouse gas emissions or better adapt plants to the changing climate would help. However, these address the symptoms, not the cause of environmental degradation. </p>
<p>Climate change is an “attractive” problem because there are so many technological ways to solve it. That quality makes societies vulnerable to the siren song of technology pushers.</p>
<p>For example, if climatic change is described as a threat to food production, then technologies that promise to increase food production despite climate change would be appealing. One such prospect is to <a href="https://academic.oup.com/jxb/article/72/11/3936/6153432">increase photosynthesis</a>. Genetic modification of the key enzyme in photosynthesis (RuBisCO) could improve its binding of carbon dioxide. More plant biomass might be the result.</p>
<figure class="align-center ">
<img alt="A leave against the sun" src="https://images.theconversation.com/files/497504/original/file-20221128-12-aa8v9d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/497504/original/file-20221128-12-aa8v9d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/497504/original/file-20221128-12-aa8v9d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/497504/original/file-20221128-12-aa8v9d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/497504/original/file-20221128-12-aa8v9d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/497504/original/file-20221128-12-aa8v9d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/497504/original/file-20221128-12-aa8v9d.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">
<figcaption>
<span class="caption">Gene-editing technologies used to increase the rate of photosynthesis may not raise crop yield.</span>
<span class="attribution"><span class="source">Shutterstock/Chyrko Olena</span></span>
</figcaption>
</figure>
<p>However, increased photosynthesis may not increase <a href="https://www.cell.com/trends/plant-science/fulltext/S1360-1385(19)30188-8">yield</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966189/">nutritional value or micronutrient levels</a> in crops. Even if this approach worked outside of the laboratory, the plants would be no less vulnerable to increasingly frequent drought and flood stresses. These plants will also demand more <a href="https://www.cell.com/trends/plant-science/fulltext/S1360-1385(19)30188-8">nitrogen fertiliser</a>, leading to more greenhouse gas emissions.</p>
<p>Maybe we could have more biomass, but not better or more food for people. Some of our crops could make better use of the additional carbon in the atmosphere, but lack of access to sufficient and desirable food would continue. By not addressing this fundamental problem, we will need more crops and livestock, undermining any efficiency gains.</p>
<h2>Technologies are not alternatives to action</h2>
<p>Implementing such technologies also prolongs <a href="https://www.smithsonianmag.com/science-nature/science-bears-fingerprints-colonialism-180968709/">colonial dependence</a> on wealthier countries and overlooks the rights and inputs of Indigenious and local peoples.</p>
<p>Identifying the fundamental social goal, rather than the proximate technological objective, is essential to achieving sustainability. “Goal pull” rather than “technology push” approaches do this.</p>
<p>Climate change is a symptom of environmental degradation and the multifarious <a href="https://www.globalcitizen.org/en/content/climate-change-is-connected-to-poverty/">complexities of poverty</a>. These are wicked problems societies find hard to address, driving up the appeal of technologies as alternatives to action. The market is good at trading in technological futures.</p>
<p>Try recasting the goal as food security, measured through indicators of reduced hunger across the world. Governments now have at their disposal solutions that include both social and technological options.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/a-shrinking-fraction-of-the-worlds-major-crops-goes-to-feed-the-hungry-with-more-used-for-nonfood-purposes-181819">A shrinking fraction of the world's major crops goes to feed the hungry, with more used for nonfood purposes</a>
</strong>
</em>
</p>
<hr>
<p>For example, reducing food waste such that more nutritious food reaches people who need it reduces demand to produce more food in the first place. <a href="https://www.washingtonpost.com/climate-solutions/2021/02/25/climate-curious-food-waste/">Food waste</a> alone will create 5.7–7.9 gigatonnes of greenhouse gas emissions by 2050. The excess nitrogen used in agriculture to produce food is also a significant source of the greenhouse gas nitrous oxide.</p>
<p>Reducing food waste depends on detailed planning to make use of technologies that are useful by design rather than opportunity. More indiscriminate production may result in <a href="https://link.springer.com/article/10.1007/s12571-014-0360-6">competition with food</a>. For example, <a href="https://www.scientificamerican.com/article/time-to-rethink-corn/">excess corn production</a> in the US resulted in much of the corn being used for non-food purposes such as bio-ethanol, despite the intensive use of resources required to produce these calories. </p>
<figure class="align-center ">
<img alt="A red barn in the middle of a corn field" src="https://images.theconversation.com/files/497501/original/file-20221128-15-pzi8ep.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/497501/original/file-20221128-15-pzi8ep.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/497501/original/file-20221128-15-pzi8ep.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/497501/original/file-20221128-15-pzi8ep.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/497501/original/file-20221128-15-pzi8ep.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/497501/original/file-20221128-15-pzi8ep.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/497501/original/file-20221128-15-pzi8ep.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Corn is used for non-food purposes such as biofuels.</span>
<span class="attribution"><span class="source">Shutterstock/christianthiel.net</span></span>
</figcaption>
</figure>
<p>Failure to meet the goal of feeding more people also provides useful feedback either about the adequacy of the strategy or the chosen measures. For example, if available calories increased but nutrition did not improve, it might be because farmers need support to develop polycultures, or healthier options should be made more accessible.</p>
<p>The goal pull approach takes us to feedback-optimised combinations of social and technological innovation that solve root problems.</p>
<p>To save a patient’s life it may be necessary to treat the symptoms of the disease. We are forced into the same situation with climate change. Nevertheless, we must not use the immediacy of climate change to put off breaking habits that will lead to future environmental and social catastrophe.</p><img src="https://counter.theconversation.com/content/194147/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Tessa Hiscox receives PhD scholarships from the University of Canterbury and the Ministry for Primary Industries. </span></em></p><p class="fine-print"><em><span>Jack Heinemann receives funding from public agencies, charities and non-governmental organisations. He is affiliated with the American Society for Microbiology, European Network of Scientists for Social Responsibility and New Zealand Microbiological Society. He has served as an expert witness for court cases relevant to biotechnology. </span></em></p>The biotech sector uses climate change as an urgent argument for more funding and fewer regulatory hurdles. But the urgency of climate change raises the risk of superficial claims and actions.Tessa Hiscox, Microbiology PhD Candidate, University of CanterburyJack Heinemann, Professor of Molecular Biology and Genetics, University of CanterburyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1843692022-06-09T12:41:46Z2022-06-09T12:41:46Z‘Jurassic World’ scientists still haven’t learned that just because you can doesn’t mean you should – real-world genetic engineers can learn from the cautionary tale<figure><img src="https://images.theconversation.com/files/467795/original/file-20220608-13-magyim.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2000%2C1500&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">While resurrecting dinosaurs may not be on the docket just yet, gene drives have the power to alter entire species. </span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/dinosaur-in-the-lab-image-what-something-new-life-royalty-free-image/1080567850">Hiroshi Watanabe/DigitalVision via Getty Images</a></span></figcaption></figure><p>“<a href="https://www.jurassicworld.com">Jurassic World: Dominion</a>” is hyperbolic Hollywood entertainment at its best, with an action-packed storyline that refuses to let reality get in the way of a good story. Yet just like its predecessors, it offers an underlying cautionary tale of technological hubris that’s very real.</p>
<p>As I discuss in my book “<a href="https://filmsfromthefuture.com/">Films from the Future</a>,”
Stephen Spielberg’s 1993 “Jurassic Park,” based on Michael Crichton’s 1990 novel, didn’t shy away from grappling with the dangers of unfettered entrepreneurship and irresponsible innovation. Scientists at the time were getting closer to being able to manipulate DNA in the real world, and both book and movie captured emerging concerns that playing God with nature’s genetic code could lead to devastating consequences. This was famously captured by one of the movie’s protagonists, Dr. Ian Malcolm, played by Jeff Goldblum, as he declared, “Your scientists were so preoccupied with whether they could, they didn’t stop to think if they should.”</p>
<hr>
<iframe id="noa-web-audio-player" style="border: none" src="https://embed-player.newsoveraudio.com/v4?key=x84olp&id=https://theconversation.com/jurassic-world-scientists-still-havent-learned-that-just-because-you-can-doesnt-mean-you-should-real-world-genetic-engineers-can-learn-from-the-cautionary-tale-184369&bgColor=F5F5F5&color=D8352A&playColor=D8352A" width="100%" height="110px"></iframe>
<p><em>You can listen to more articles from The Conversation, narrated by Noa, <a href="https://theconversation.com/us/topics/audio-narrated-99682">here</a>.</em></p>
<hr>
<p>In the latest iteration of the “Jurassic Park” franchise, society is coming to terms with the consequences of innovations that were, at best, ill-conceived. A litany of “coulds” over “shoulds” has led to a future in which resurrected and redesigned dinosaurs roam free, and humanity’s dominance as a species is under threat. </p>
<p>At the heart of these films are questions that are more relevant than ever: Have researchers learned the lesson of “Jurassic Park” and sufficiently closed the gap between “could” and “should”? Or will the science and technology of DNA manipulation continue to outpace any consensus on how to use them ethically and responsibly?</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/NkEU6fC_nhY?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Imagine a world where dinosaurs and humans coexist.</span></figcaption>
</figure>
<h2>(Re)designing the genome</h2>
<p>The first draft of the human genome <a href="https://doi.org/10.1038/35057062">was published to great fanfare</a> in 2001, setting the stage for scientists to read, redesign and even rewrite complex genetic sequences. </p>
<p>However, existing technologies were time-consuming and expensive, placing genetic manipulation out of reach for many researchers. The first draft of the human genome cost an estimated <a href="https://www.genome.gov/about-genomics/fact-sheets/DNA-Sequencing-Costs-Data">US$300 million</a>, and subsequent whole-genome sequences just under $100 million – a prohibitive amount for all but the most well-funded research groups. As existing technologies were refined and new ones came online, however, smaller labs – and even <a href="https://igem.org/">students</a> and <a href="https://www.wired.com/2014/11/diybio-comes-of-age/">“DIY bio” hobbyists</a> – could experiment more freely with reading and writing genetic code.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/467797/original/file-20220608-22-ddjvfi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A DIY bio lab with equipment arranged on counters and cabinets against the walls." src="https://images.theconversation.com/files/467797/original/file-20220608-22-ddjvfi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/467797/original/file-20220608-22-ddjvfi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=449&fit=crop&dpr=1 600w, https://images.theconversation.com/files/467797/original/file-20220608-22-ddjvfi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=449&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/467797/original/file-20220608-22-ddjvfi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=449&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/467797/original/file-20220608-22-ddjvfi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=564&fit=crop&dpr=1 754w, https://images.theconversation.com/files/467797/original/file-20220608-22-ddjvfi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=564&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/467797/original/file-20220608-22-ddjvfi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=564&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">You can manipulate DNA in the comfort of your own home-based DIY bio lab.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/macowell/4821488307/in/pool-diylabs/">Mackenzie Cowell/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>In 2005, bioengineer Drew Endy proposed that it should be possible to work with DNA the <a href="https://doi.org/10.1038/nature04342">same way that engineers work with electronic components</a>. Much as electronics designers are less concerned with the physics of semiconductors than they are with the components that rely on them, Endy argued that it should be possible to create standardized DNA-based parts called “<a href="https://biobricks.org/">biobricks</a>” that scientists could use without needing to be experts in their underlying biology.</p>
<p>Endy’s and others’ work was foundational to the emerging field of <a href="https://doi.org/10.1038/nrmicro3239">synthetic biology</a>, which applies engineering and design principles to genetic manipulation. </p>
<p>Scientists, engineers and even <a href="https://www.vice.com/en/article/9anmk7/bioart-synthetic-biology-projects">artists</a> began to approach DNA as a biological code that could be digitized, manipulated and redesigned in cyberspace in much the same way as digital photos or videos are. This in turn opened the door to reprogramming plants, microorganisms and fungi to produce <a href="https://doi.org/10.2147/DDDT.S58049">pharmaceutical drugs</a> and other <a href="https://fortune.com/2021/08/06/synthetic-biology-plant-based-meats-bioengineering-environmental-impact/">useful substances</a>. Modified yeast, for example, produces the meaty taste of vegetarian <a href="https://doi.org/10.1038/s41467-020-20122-2">Impossible Burgers</a>.</p>
<p>Despite increasing interest in gene editing, the biggest barrier to the imagination and vision of the early pioneers of synthetic biology was still the speed and cost of editing technologies.</p>
<p>Then CRISPR changed everything.</p>
<h2>The CRISPR revolution</h2>
<p>In 2020, scientists Jennifer Doudna and Emanuelle Charpentier won the <a href="https://doi.org/10.1038/d41586-020-02765-9">Nobel Prize in chemistry</a> for their work on a revolutionary new gene-editing technology that allows researchers to precisely snip out and replace DNA sequences within genes: CRISPR.</p>
<p>CRISPR was quick, cheap and relatively easy to use. And it unleashed the imagination of DNA coders.</p>
<p>More than any previous advance in genetic engineering, CRISPR enabled techniques from digital coding and systems engineering to be applied to biology. This cross-fertilization of ideas and methods led to breakthroughs ranging from using <a href="https://www.smithsonianmag.com/smart-news/scientists-write-hello-world-bacterial-dna-electricity-and-crispr-180976763/">DNA to store computer data</a> to creating 3D “<a href="https://www.advancedsciencenews.com/crispr-cleans-up-dna-origami/">DNA origami” structures</a>.</p>
<p>CRISPR also opened the way for scientists to explore redesigning entire species – including <a href="https://www.npr.org/sections/pictureshow/2013/03/15/174322143/its-called-de-extinction-its-like-jurassic-park-except-its-real">bringing back animals from extinction</a>.</p>
<p><a href="https://doi.org/10.1038/d41586-019-02087-5">Gene drives</a> use CRISPR to directly insert a piece of genetic code into an organism’s genome and ensure that specific traits are inherited by all subsequent generations. Scientists are currently experimenting with this technology to <a href="https://doi.org/10.1038/d41586-021-01186-6">control disease-carrying mosquitoes</a>. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/KgvhUPiDdq8?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Gene drives have the potential to alter the genetic makeup of an entire species.</span></figcaption>
</figure>
<p>Despite the potential benefits of the technology, gene drives raise serious ethical questions. Even when applied to clear public health threats like mosquitoes, <a href="https://www.nytimes.com/2020/01/08/magazine/gene-drive-mosquitoes.html">these questions are not easy to navigate</a>. They get even more complex when considering hypothetical applications in people, such as <a href="https://slate.com/technology/2019/12/crispr-prime-editing-gene-doping-athletes.html">increasing athletic performance in future generations</a>.</p>
<h2>Gain of function</h2>
<p>Advances in gene editing have also made it easier to genetically alter the behavior of individual cells. This is at the heart of <a href="https://www.weforum.org/agenda/2021/12/how-to-fuel-the-biomanufacturing-revolution/">biomanufacturing technologies</a> that reengineer simple organisms to produce useful substances ranging from <a href="https://simpleflying.com/united-airlines-jet-fuel-from-thin-air/">aviation fuel</a> to <a href="https://www.foodnavigator-usa.com/Article/2022/05/09/Synthetic-biology-and-the-future-of-food.-In-conversation-with-biology-by-design-co-Ginkgo-Bioworks">food additives</a>. </p>
<p>It’s also at the center of controversies surrounding genetically engineered viruses.</p>
<p>Since the beginning of the pandemic, there have been rumors that the virus that causes COVID-19 resulted from genetic experiments gone wrong. While these rumors <a href="https://www.newyorker.com/science/elements/the-mysterious-case-of-the-covid-19-lab-leak-theory">remain unsubstantiated</a>, they’ve renewed debate around the <a href="https://www.nytimes.com/2021/06/20/science/covid-lab-leak-wuhan.html">ethics of gain-of-function research</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/467800/original/file-20220608-20-kw2z6q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Gloved hands holding biohazard sample in lab" src="https://images.theconversation.com/files/467800/original/file-20220608-20-kw2z6q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/467800/original/file-20220608-20-kw2z6q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/467800/original/file-20220608-20-kw2z6q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/467800/original/file-20220608-20-kw2z6q.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/467800/original/file-20220608-20-kw2z6q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=425&fit=crop&dpr=1 754w, https://images.theconversation.com/files/467800/original/file-20220608-20-kw2z6q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=425&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/467800/original/file-20220608-20-kw2z6q.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=425&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Modifying the genetic makeup of organisms and pathogens has both risks and benefits.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/arselectronica/36320619976">Ars Electronica/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<p><a href="https://theconversation.com/why-gain-of-function-research-matters-162493">Gain-of-function</a> research uses DNA editing techniques to alter how organisms function, including increasing the ability of viruses to cause disease. Scientists do this to predict and prepare for potential mutations of existing viruses that increase their ability to cause harm. However, such research also raises the possibility of a dangerously enhanced virus’s being released outside the lab, either accidentally or intentionally.</p>
<p>At the same time, scientists’ increasing mastery over biological source code is what has allowed them to <a href="https://www.weforum.org/agenda/2021/07/everything-you-need-to-know-about-mrna-vaccines/">rapidly develop the Pfizer-BioNTech and Moderna mRNA vaccines</a> to combat COVID-19. By precisely engineering the genetic code that instructs cells to produce harmless versions of viral proteins, vaccines are able to prime the immune system to respond when it encounters the actual virus.</p>
<h2>Responsible biological source code manipulation</h2>
<p>Prescient as Michael Crichton was, it’s unlikely that he could have envisioned just how far scientists’ abilities to engineer biology have advanced over the past three decades. <a href="https://www.smithsonianmag.com/science-nature/these-are-extinct-animals-we-can-should-resurrect-180954955/">Bringing back extinct species</a>, while an active area of research, remains <a href="https://doi.org/10.3390%2Fgenes9110548">fiendishly difficult</a>. However, in many ways, our technologies are substantially further along than those in “Jurassic Park” and the subsequent films.</p>
<p>But how have we done on the responsibility front?</p>
<p>Fortunately, consideration of the social and ethical side of gene editing has gone hand in hand with the science’s development. In 1975, scientists <a href="https://doi.org/10.1073/pnas.72.6.198">agreed on approaches</a> to ensure that emerging recombinant DNA research would be carried out safely. From the get-go, the ethical, legal and social dimensions of the science were hard-wired into the <a href="https://www.genome.gov/Funded-Programs-Projects/ELSI-Research-Program-ethical-legal-social-implications">Human Genome Project</a>. DIY bio communities have been at the forefront of <a href="https://doi.org/10.1038/531167a">safe and responsible gene-editing research</a>. And social responsibility is integral to <a href="https://blog.igem.org/blog/2020/9/23/igem-and-the-value-of-responsibility">synthetic biology competitions</a>. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/12VfS2hAi7c?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">DNA was never destiny.</span></figcaption>
</figure>
<p>Yet as gene editing becomes increasingly powerful and accessible, a community of well-meaning scientists and engineers is unlikely to be sufficient. While the “Jurassic Park” movies take dramatic license in their portrayal of the future, they do get one thing right: Even with good intentions, bad things happen when you mix powerful technologies with scientists who haven’t been trained to think through the consequences of their actions – and haven’t thought to ask experts who have.</p>
<p>Maybe this is the abiding message of “Jurassic World: Dominion” – that despite incredible advances in genetic design and engineering, things can and will go wrong if we don’t embrace the development and use of the technology in socially responsible ways.</p>
<p>The good news is that we still have time to close the gap between “could” and “should” in how scientists redesign and reengineer genetic code. But as “Jurassic World: Dominion” reminds moviegoers, the future is often closer than it might appear.</p><img src="https://counter.theconversation.com/content/184369/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andrew Maynard 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>As genetic engineering and DNA manipulation tools like CRISPR continue to advance, the distinction between what science ‘could’ and ‘should’ do becomes murkier.Andrew Maynard, Professor of Responsible Innovation, Arizona State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1752262022-01-25T19:03:20Z2022-01-25T19:03:20ZSome endangered species can no longer survive in the wild. So should we alter their genes?<figure><img src="https://images.theconversation.com/files/442159/original/file-20220124-17-fdh2zz.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1650%2C930&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Melbourne Zoo</span></span></figcaption></figure><p>Around the world, populations of many beloved species are declining at increasing rates. According to one <a href="https://www.theguardian.com/environment/2020/sep/30/world-plant-species-risk-extinction-fungi-earth">grim projection</a>, as many as 40% of the world’s species may be extinct by 2050. Alarmingly, many of these declines are caused by threats for which few solutions exist.</p>
<p>Numerous species now depend on conservation breeding programs for their survival. But these programs typically do not encourage species to adapt and survive in the wild alongside intractable threats such as climate change and disease.</p>
<p>This means some species can no longer exist in the wild, which causes major downstream effects on the ecosystem. Consider, for example, how a coral reef would struggle to function without corals.</p>
<p>What if there was another way? My colleagues and I have developed an intervention method that aims to give endangered species the genetic features they need to survive in the wild.</p>
<figure class="align-center ">
<img alt="bleached coral with fish" src="https://images.theconversation.com/files/411140/original/file-20210714-13-1bf7ccv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/411140/original/file-20210714-13-1bf7ccv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=320&fit=crop&dpr=1 600w, https://images.theconversation.com/files/411140/original/file-20210714-13-1bf7ccv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=320&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/411140/original/file-20210714-13-1bf7ccv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=320&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/411140/original/file-20210714-13-1bf7ccv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=402&fit=crop&dpr=1 754w, https://images.theconversation.com/files/411140/original/file-20210714-13-1bf7ccv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=402&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/411140/original/file-20210714-13-1bf7ccv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=402&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Genetically altering coral may help them survive in a warmer world.</span>
<span class="attribution"><span class="source">Rick Stuart-Smith</span></span>
</figcaption>
</figure>
<h2>Bringing theory into practice</h2>
<p>Over generations, natural selection enables species to adapt to threats. But in many instances today, the speed at which threats are developing is outpacing species’ ability to adapt. </p>
<p>This problem is especially apparent in wildlife threatened by newly emerging infectious diseases such as chytridiomycosis in amphibians, and in climate-affected species such as corals. </p>
<p>The toolkit my colleagues and I developed is called “targeted genetic intervention” or TGI. It works by increasing the occurrence or frequency of genetic features that impact an organism’s fitness in the presence of the threat. We outline the method in a recent <a href="https://www.sciencedirect.com/science/article/abs/pii/S0169534721003384">research paper</a>.</p>
<p>The toolkit involves <a href="https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/artificial-selection">artificial selection</a> and <a href="https://www.frontiersin.org/articles/10.3389/fbioe.2019.00175/full">synthetic biology</a>. These tools are well established in agriculture and medicine but relatively untested as conservation tools. We explain them in more detail below.</p>
<p>Many tools in our TGI toolkit have been discussed in theory in conservation literature in recent decades. But rapid developments in genome sequencing and synthetic biology mean some are now possible in practice.</p>
<p>The developments have made it easier to understand the genetic basis of features which enable a species to adapt, and to manipulate them.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/we-name-the-26-australian-frogs-at-greatest-risk-of-extinction-by-2040-and-how-to-save-them-166339">We name the 26 Australian frogs at greatest risk of extinction by 2040 — and how to save them</a>
</strong>
</em>
</p>
<hr>
<figure class="align-center ">
<img alt="frog on wet rock" src="https://images.theconversation.com/files/442166/original/file-20220124-19-xc82dx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/442166/original/file-20220124-19-xc82dx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/442166/original/file-20220124-19-xc82dx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/442166/original/file-20220124-19-xc82dx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/442166/original/file-20220124-19-xc82dx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/442166/original/file-20220124-19-xc82dx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/442166/original/file-20220124-19-xc82dx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Some animal species cannot adapt in time to survive threats such as disease.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<h2>What is artificial selection?</h2>
<p>Humans have long used artificial (or phenotypic) selection to promote desirable characteristics in animals and plants raised for companionship or food. This genetic alteration has led to organisms, such as domestic dogs and maize, that are dramatically different from their wild progenitors.</p>
<p>Traditional artificial selection can lead to outcomes, such as high inbreeding rates, that affect the health and resilience of the organism and are undesirable for conservation. If you’ve ever owned a purebred dog, you might be aware of some of these genetic disorders.</p>
<p>And when it comes to conservation, determining which individuals from a species are resistant to, say, a deadly pathogen would involve exposing the animal to the threat – clearly not in the interests of species preservation.</p>
<p>Scientists in the livestock industry have developed a new approach to circumvent these problems. Called genomic selection, it combines data from laboratory work (such as a disease trial) with the genetic information of the animals to predict which individuals bear genetic features conducive to adaptation. </p>
<p>These individuals are then chosen for breeding. Over subsequent generations, a population’s ability to survive alongside pervasive threats increases.</p>
<p>Genomic selection has led to disease-resistant salmon and livestock that produce more milk and better tolerate heat. But it is yet to be tested in conservation.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-this-little-marsupials-poo-nurtures-urban-gardens-and-bushland-and-how-you-can-help-protect-them-175064">How this little marsupial's poo nurtures urban gardens and bushland (and how you can help protect them)</a>
</strong>
</em>
</p>
<hr>
<figure class="align-center ">
<img alt="cows in green field" src="https://images.theconversation.com/files/442161/original/file-20220124-27-11vyq0z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/442161/original/file-20220124-27-11vyq0z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/442161/original/file-20220124-27-11vyq0z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/442161/original/file-20220124-27-11vyq0z.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/442161/original/file-20220124-27-11vyq0z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/442161/original/file-20220124-27-11vyq0z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/442161/original/file-20220124-27-11vyq0z.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Artificial selection has been used to develop traits that humans desire in livestock.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<h2>What is synthetic biology?</h2>
<p><a href="https://www.genome.gov/about-genomics/policy-issues/Synthetic-Biology">Synthetic biology</a> is a toolkit for promoting change in organisms. It includes methods such as transgenesis and gene editing, which can be used to introduce lost or novel genes or tweak specific genetic features. </p>
<p>Recent synthetic biology tools such as <a href="https://medlineplus.gov/genetics/understanding/genomicresearch/genomeediting/">CRISPR-Cas9</a> have created a buzz in the medical world, and are also starting to gain the <a href="https://portals.iucn.org/library/node/48408">attention</a> of conservation biologists.</p>
<p>Such tools can accurately tweak targeted genetic features in an individual organism – making it more able to adapt – while leaving the rest of the genome untouched. The genetic modifications are then passed on to subsequent generations.</p>
<p>The method reduces the likelihood of unintended genetic changes that can occur with artificial selection.</p>
<p>Synthetic biology methods are currently being trialled for conservation in multiple species around the world. These include the <a href="https://www.esf.edu/chestnut/resistance.htm">chestnut tree</a> and black-footed <a href="https://neo.life/2021/05/cloning-wildlife-and-editing-their-genes-to-protect-them-and-us/">ferrets</a> in the United States, and <a href="https://theconversation.com/gene-editing-is-revealing-how-corals-respond-to-warming-waters-it-could-transform-how-we-manage-our-reefs-143444">corals</a> in Australia.</p>
<p>I am working with researchers at the University of Melbourne to develop TGI approaches in Australian frogs. We are trialling these approaches in the iconic southern corroboree frog, and plan to extend them to other species if they prove effective.</p>
<p>Worldwide, the disease chytridiomycosis is devastating frog populations. Caused by the fungal pathogen <em>Batrachochytrium dendrobatidis</em>, it has led to the extinction of about <a href="https://www.nationalgeographic.com/animals/article/amphibian-apocalypse-frogs-salamanders-worst-chytrid-fungus">90 frog species</a> and declines in as many as 500 others.</p>
<p>Many frog species now rely on conservation breeding for their continued survival. No effective solution for restoring chytrid-susceptible frogs to the wild exists, because the fungus cannot be eradicated.</p>
<figure class="align-center ">
<img alt="gloved hand removed portion of DNA strand" src="https://images.theconversation.com/files/442155/original/file-20220124-23-cebr8a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/442155/original/file-20220124-23-cebr8a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/442155/original/file-20220124-23-cebr8a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/442155/original/file-20220124-23-cebr8a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/442155/original/file-20220124-23-cebr8a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/442155/original/file-20220124-23-cebr8a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/442155/original/file-20220124-23-cebr8a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">CRISPR technology could potentially be used to edit the genes of endangered species.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<h2>Looking ahead</h2>
<p>As with many conservation approaches, targeted genetic intervention is likely to involve trade-offs. For example, genetic features that make a species resistant to one disease may make it more susceptible to another.</p>
<p>But the rapid rate of species declines means we should trial such potential solutions before it’s too late. The longer species are absent from an ecosystem, the greater the chance of irreversible environmental changes. </p>
<p>Any genetic intervention of this type should involve all stakeholders, including Indigenous peoples and local communities. And caution should be taken to ensure species are fit for release and pose no risk to the environment.</p>
<p>By bringing the concept of TGI to the attention of the public, government, and other scientists, we hope we will spur discussion and encourage research on its risks and benefits.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/5-major-heatwaves-in-30-years-have-turned-the-great-barrier-reef-into-a-bleached-checkerboard-170719">5 major heatwaves in 30 years have turned the Great Barrier Reef into a bleached checkerboard</a>
</strong>
</em>
</p>
<hr>
<img src="https://counter.theconversation.com/content/175226/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Tiffany Kosch is a member of One Health Research Group at the University of Melbourne. Her research is currently funded by the Australian Research Council (grants FT190100462 and LP200301370). Additionally, the genome of their target species, the Southern Corroboree frog is currently being sequenced at no cost to the group by the Vertebrate Genomes Project. </span></em></p>The rapid rate of species declines means we should trial potential solutions before it’s too late.Tiffany Kosch, Research Fellow, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1713432021-11-12T15:25:23Z2021-11-12T15:25:23ZZombie apocalypse? How gene editing could be used as a weapon – and what to do about it<figure><img src="https://images.theconversation.com/files/431659/original/file-20211112-23-187k38x.jpg?ixlib=rb-1.1.0&rect=80%2C80%2C4412%2C2910&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Probably not...</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/zombie-crowd-walking-nighthalloween-conceptillustration-painting-454095508"> Tithi Luadthong/Shutterstock</a></span></figcaption></figure><p>It has been over a year since the World Health Organisation (WHO) declared COVID-19 a pandemic. And perhaps the most important lesson is that we were completely unprepared to face the debilitating virus. </p>
<hr>
<iframe id="noa-web-audio-player" style="border: none" src="https://embed-player.newsoveraudio.com/v4?key=x84olp&id=https://theconversation.com/zombie-apocalypse-how-gene-editing-could-be-used-as-a-weapon-and-what-to-do-about-it-171343&bgColor=F5F5F5&color=D8352A&playColor=D8352A" width="100%" height="110px"></iframe>
<p><em>You can listen to more articles from The Conversation, narrated by Noa, <a href="https://theconversation.com/uk/topics/audio-narrated-99682">here</a>.</em></p>
<hr>
<p>This raises some scary thoughts. What if the threat wasn’t COVID-19, but a gene-edited pathogen designed to turn us into zombies – ghost-like, agitated creatures with little awareness of our surroundings? With recent advances in gene editing, it may be possible for bioterrorists to design viruses capable of altering our behaviour, spreading such a disease and ultimately killing us. And chances are we still wouldn’t be sufficiently prepared to deal with it. </p>
<p>A zombie apocalypse may sound far-fetched, reserved for the annals of graphic novels, immersive gaming experiences and popular culture. But there are examples of <a href="https://www.scientificamerican.com/store/ebooks/the-real-zombies-of-nature/">“zombification” in nature</a>. Perhaps the most well known is rabies, which can cause aggression and hallucination and is almost always fatal once symptoms appear. </p>
<p>But there are others. A recently discovered kind of wasp, for example, can turn a particular species of spider (<em>Anelosimus eximius</em>) <a href="https://www.sciencedaily.com/releases/2018/11/181127092541.htm">into “zombies”</a> by laying eggs on their abdomen. The resulting larvae then attaches itself to the spider, feeding on it, while the spider, once a social individual, leaves the colony and prepares to die alone. Other <a href="https://www.businessinsider.com/zombies-in-nature-science-2019-5?r=US&IR=T#the-animal-kingdom-also-boasts-a-few-examples-of-the-type-of-external-control-that-the-night-king-exerts-over-his-wights-in-game-of-thrones-parasitic-fungi-for-instance-can-enslave-ants-5">zombification examples</a> from nature include the African sleeping sickness, a fatal neurological condition created by insect-borne parasites, and the <a href="https://www.nature.com/articles/s41598-020-63400-1"><em>Ophiocordyceps unilateralis</em></a> fungus, which changes the behaviour of carpenter ants before killing them and sprouting out of their heads.</p>
<figure class="align-center ">
<img alt="Image of an ant with Cordyceps." src="https://images.theconversation.com/files/431675/original/file-20211112-1788-80t20e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/431675/original/file-20211112-1788-80t20e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=402&fit=crop&dpr=1 600w, https://images.theconversation.com/files/431675/original/file-20211112-1788-80t20e.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=402&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/431675/original/file-20211112-1788-80t20e.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=402&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/431675/original/file-20211112-1788-80t20e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=505&fit=crop&dpr=1 754w, https://images.theconversation.com/files/431675/original/file-20211112-1788-80t20e.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=505&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/431675/original/file-20211112-1788-80t20e.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">
<figcaption>
<span class="caption">Ant with fungus.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/ant-cordyceps-31294987">Shutterstock</a></span>
</figcaption>
</figure>
<h2>Weaponising pathogens</h2>
<p>Last year, the Nobel Prize in Chemistry <a href="https://theconversation.com/nobel-prize-two-women-share-chemistry-prize-for-the-first-time-for-work-on-genetic-scissors-147721">recognised</a> the development of a type of genetic scissors <a href="https://www.sciencedirect.com/science/article/pii/S0092867414006047">called CRISPR-Cas9</a>. Interest in this technology has been simmering for a while, with equal doses of excitement and fear. Because of its ability to edit the human genome <a href="https://link.springer.com/book/10.1007/978-3-030-22308-3">with unprecedented precision</a>, replacing a single letter in the DNA, CRISPR has already proven itself useful in treating genetic conditions such as sickle cell disease, beta thalassemia, and many others. </p>
<p>But CRISPR-Cas9 could theoretically also be used for darker purposes, such as bioterrorism. It could alter pathogens to make them more transmissible or fatal. Alternatively, it could turn a non-pathogen, such as a harmless microbe, into an aggressive virus. The technique may even be able to alter a virus to make it dangerous for a larger range of species than it currently infects, or make it resistant to antibiotics or antivirals.</p>
<p>Whether CRISPR could be used to infect humans in a way to make them zombie-like remains a theoretical speculation. At the moment, there are probably easier ways to terrorise people. But as biotechnologies improve in the wake of COVID, the risk from bioterrorism is increasing. </p>
<p>If a zombie-like disease could be created, it clearly wouldn’t make deceased people reawaken as zombies. But an infection that passed through saliva with extremely high transmission and mortality rate, and which caused agitation, destructive behaviour and death, wouldn’t be far off the horror that we see in zombie movies. Such a virus would spread rapidly from human to human in a similar manner to diseases such as <a href="https://www.cdc.gov/vhf/ebola/index.html">Ebola</a> and <a href="https://www.who.int/news-room/fact-sheets/detail/marburg-virus-disease">Marburg</a> viruses. In the epic zombie film, <a href="https://www.imdb.com/title/tt0289043/">28 Days Later</a>, the fictitious “rage virus” was, in fact, inspired by these two real-life viruses.</p>
<p>Given these possibilities, it is not surprising that the director of the US National Intelligence, James Clapper, <a href="https://www.technologyreview.com/2016/02/09/71575/top-us-intelligence-official-calls-gene-editing-a-wmd-threat/">termed gene editing</a> “weapons of mass destruction and proliferation” in 2018. </p>
<figure class="align-center ">
<img alt="Image of genetic code with the letters CRISPR in the middle" src="https://images.theconversation.com/files/431660/original/file-20211112-21-1fjd638.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/431660/original/file-20211112-21-1fjd638.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=430&fit=crop&dpr=1 600w, https://images.theconversation.com/files/431660/original/file-20211112-21-1fjd638.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=430&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/431660/original/file-20211112-21-1fjd638.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=430&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/431660/original/file-20211112-21-1fjd638.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=540&fit=crop&dpr=1 754w, https://images.theconversation.com/files/431660/original/file-20211112-21-1fjd638.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=540&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/431660/original/file-20211112-21-1fjd638.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=540&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">CRISPR can alter single letters in DNA.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/crispr-locus-on-dna-sequence-693879967">Shuttesrstock</a></span>
</figcaption>
</figure>
<p>Many countries are aware of the risks. In 2018, the US government released its <a href="https://www.phe.gov/Preparedness/biodefense-strategy/Pages/default.aspx">first bio-defence strategy</a>, involving multiple government agencies. The plan covers not only deliberate bioterror threats, but also “naturally occurring outbreaks and infectious diseases that escape a lab accidentally”. And, curiously, the US Department of Defense Strategic Command unit has issued a training programme called <a href="https://www.stratcom.mil/Portals/8/Documents/FOIA/CONPLAN_8888-11.pdf?ver=2016-10-17-114016-887">CONOP 8888 (Counter-Zombie Dominance)</a>, which simulates a zombie apocalypse situation. However, this was designed to be completely fictitious, providing military and defence training without the need to involve real, classified information.</p>
<h2>How to stop it</h2>
<p>Do we stand a chance against such gene-edited pathogens? We have <a href="https://www.un.org/disarmament/publications/library/">international law conventions</a> on biological and chemical toxins. These strictly prohibit states from acquiring or retaining biological weapons. But it is questionable whether these are adequate in the face of novel approaches. Gene editing technologies such as CRISPR are getting cheaper and easier to work with. That means rogue scientists or organisations could use them for bioterrorism.</p>
<p>Ideally, specific provisions in these international instruments should be revisited and adapted to the changing environment. This may include imposing a moratorium on experimenting with gene editing as biological weapon tools or allowing experimentation strictly for benefiting human health.</p>
<p>In June, a WHO expert committee published two reports (see <a href="https://www.who.int/publications/i/item/9789240030381">here</a> and <a href="https://www.who.int/publications/i/item/9789240030060">here</a>) that made recommendations about how human genome editing could be governed at the appropriate institutional, national and global level. Its framework incorporates structures of governance that already exist in different countries, such as regulatory authorities or national guidelines regarding genome editing or similar technologies. It recommends, for example, that ethics committees review clinical trials and approvals in the area.</p>
<p>While these recommendations provide some clarity, it is concerning that these are simply guidelines that do not have the force of law. The WHO is not in a position to regulate genome editing in individual countries. It therefore becomes incumbent on individual countries to implement these recommendations as part of their own national law. Another problem is that the guidelines do not address issues of safety and efficacy – stating this wasn’t part of the scope of the review. But that may change going forward. </p>
<p>For now, these recommendations are the closest thing we have to a global framework of governance. And as the technology continues to develop, it is hoped that they will also evolve accordingly. But ultimately, we may need to think about how to make such frameworks legally binding.</p>
<p>If all else fails, we might have to start working on our cardio and survival skills, and take a leaf out of the books of <a href="https://theconversation.com/we-spoke-to-survivalists-prepping-for-disaster-heres-what-we-learned-about-the-end-of-the-world-118867">survivalist preppers</a>.</p><img src="https://counter.theconversation.com/content/171343/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Pin Lean Lau is affiliated with the Interest Group of Supranational Bio-Law of the European Association of Health Law (EAHL). </span></em></p>Rabies, for example, is a naturally occurring ‘zombie’ disease.Pin Lean Lau, Lecturer in Bio-Law, Brunel Law School | Centre for Artificial Intelligence: Social & Digital Innovations, Brunel University LondonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1714562021-11-10T19:11:16Z2021-11-10T19:11:16ZGenetic GPS system of animal development explains why limbs grow from torsos and not heads<figure><img src="https://images.theconversation.com/files/431177/original/file-20211109-25-10ge7mq.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C703%2C496&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">New research in fruit flies elucidates how the genes that direct animal body shape work.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/close-up-of-insect-head-royalty-free-image/707582343">Vaclav Hykes/EyeEm via Getty Images</a></span></figcaption></figure><p>Why do human look like humans, rather than like chimps? Although we <a href="https://www.science.org/content/article/bonobos-join-chimps-closest-human-relatives">share 99% of our DNA</a> with chimps, our faces and bodies look quite different from each other.</p>
<p>While human body shape and appearance have clearly changed during the course of evolution, some of the genes that control the defining characteristics of different species surprisingly have not. As a <a href="https://biology.ucsd.edu/research/faculty/ebier">biologist studying evolution and development</a>, I have devoted many years to pondering how genes actually make people and other animals look the way they do. </p>
<p><a href="https://doi.org/10.1126/sciadv.abk1003">New research</a> from my lab on how these genes work has shed some light on how genes that have remained unchanged for hundreds of thousands of years can still alter the appearance of different species as they evolve.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1195486216843513856"}"></div></p>
<h2>Heads versus tails</h2>
<p>In biology, a <a href="https://doi.org/10.1242/dev.039651">body plan</a> describes how an animal’s body is organized from head to toe – or tail. All animals with <a href="https://courses.lumenlearning.com/boundless-biology/chapter/features-used-to-classify-animals/">bilateral symmetry</a>, meaning their left and right sides are mirror images, share similar body plans. For example, the head forms at the anterior end, limbs form in the mid-body, and the tail forms at the posterior end.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/431128/original/file-20211109-15-z4had2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram of three body plan symmetries of animals (asymmetrical, radial and bilateral)." src="https://images.theconversation.com/files/431128/original/file-20211109-15-z4had2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/431128/original/file-20211109-15-z4had2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=247&fit=crop&dpr=1 600w, https://images.theconversation.com/files/431128/original/file-20211109-15-z4had2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=247&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/431128/original/file-20211109-15-z4had2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=247&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/431128/original/file-20211109-15-z4had2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=311&fit=crop&dpr=1 754w, https://images.theconversation.com/files/431128/original/file-20211109-15-z4had2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=311&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/431128/original/file-20211109-15-z4had2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=311&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Animals in the same species usually share the same symmetry. Humans and goats have bilateral symmetry, meaning they can be divided into halves that are mirror images of each other.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Figure_33_01_01.jpg">CNX OpenStax/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p><a href="https://doi.org/10.1038/nrg1726">Hox genes</a> play an important role in setting up this body plan. This group of genes is a subset of genes involved in anatomical development called <a href="https://doi.org/10.1016/0092-8674(92)90471-n">homeobox genes</a>. They act like a genetic GPS system, determining what each body segment will turn into during development. They ensure that your limbs grow from your torso instead of from your head by controlling other genes that instruct the formation of specific body parts. </p>
<p>All animals have Hox genes and express them in similar body regions. Furthermore, these genes haven’t changed throughout evolutionary history. How can these genes remain so stable over such vast evolutionary time spans, yet play such pivotal roles in animal development?</p>
<h2>Blast from the past</h2>
<p>In 1990, molecular biologist <a href="https://biology.ucsd.edu/research/faculty/wmcginnis">William McGinnis</a> and his research team wondered whether the Hox genes from one species might function similarly in another species. After all, these genes are active in similar body regions in animals ranging from fruit flies to humans and mice.</p>
<p>This was a bold idea. As an analogy, consider cars: Most car parts typically are not interchangeable between different makes. The <a href="https://www.loc.gov/everyday-mysteries/item/who-invented-the-automobile/">first automobile</a> was only invented around 100 years ago. Compare that to flies and mammals, whose <a href="https://doi.org/10.1534/genetics.114.171785">last common ancestor</a> lived over 500 million years ago. It was virtually unthinkable that swapping genes from different species that diverged from each other over such a vast period of time could work.</p>
<p>Nonetheless, McGinnis and his team went ahead with their experiment and inserted mouse or human Hox genes into fruit flies. They then activated the genes in the wrong corresponding areas of the body – for instance, placing the Hox gene that tells a human leg where to develop at the very front of a fruit fly’s head. A misplaced body part would indicate that the mouse or human Hox genes were functioning like the fruit fly’s own genes would have.</p>
<p>Remarkably, both <a href="https://doi.org/10.1016/0092-8674(90)90499-5">mouse</a> and <a href="https://doi.org/10.1016/0092-8674(90)90500-E">human</a> Hox genes transformed the fruit fly antennae into legs. This meant that the positional information provided by the human and mouse genes was still recognized in the fly, millions of years later.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1195489028549660678"}"></div></p>
<h2>How do Hox genes really work?</h2>
<p>The next big question, then, was how exactly do these Hox genes determine the identities of different body regions?</p>
<p>There have been two schools of thought on how Hox genes work. The first, called the <a href="https://doi.org/10.1038/nrg2417">instructive hypothesis</a>, proposes that these shape-controlling genes function as “master” regulatory genes that supply the body instructions on how to develop different body parts. </p>
<p>The second, proposed by McGinnis, hypothesizes that Hox genes instead provide a <a href="https://doi.org/10.1038/nrg1726">positional code</a> that marks particular locations in the body. Genes can use these codes to produce specific body structures at those locations. Over the course of evolution, specific body parts come under the control of a specific Hox gene in a way that would best maximize the organism’s survival. This is why flies develop antennae rather than legs on their heads, and humans have collar bones below instead of above their necks.</p>
<p>In a <a href="https://doi.org/10.1126/sciadv.abk1003">recent study</a> published in the journal Science Advances, a mentee of McGinnis and myself, <a href="https://scholar.google.com/citations?user=aQAMm3kAAAAJ&hl=en">Ankush Auradkar</a>, puts these hypotheses to the test on fruit flies.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/431136/original/file-20211109-13-xlwasg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram showing Drosophola Hox genes and their corresponding body parts." src="https://images.theconversation.com/files/431136/original/file-20211109-13-xlwasg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/431136/original/file-20211109-13-xlwasg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=420&fit=crop&dpr=1 600w, https://images.theconversation.com/files/431136/original/file-20211109-13-xlwasg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=420&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/431136/original/file-20211109-13-xlwasg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=420&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/431136/original/file-20211109-13-xlwasg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=527&fit=crop&dpr=1 754w, https://images.theconversation.com/files/431136/original/file-20211109-13-xlwasg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=527&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/431136/original/file-20211109-13-xlwasg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=527&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Each Hox gene is linked to a specific body part. The proboscipedia gene, or pb, for instance, directs formation of a fruit fly’s mouthparts.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Hox-genes-drosophila.jpg">Antonio Quesada Díaz/Wikimedia Commons</a></span>
</figcaption>
</figure>
<p>Auradkar focused on a fruit fly Hox gene called proboscipedia (<em>pb</em>), which directs the formation of the fly’s mouthparts. He used <a href="https://medlineplus.gov/genetics/understanding/genomicresearch/genomeediting/">CRISPR-based genome editing</a> to replace the <em>pb</em> gene from the common laboratory variety of fruit fly, <em>Drosophila melanogaster</em>, or <em>D. mel</em> for short, with its Hawaiian cousin, <em>Drosophila mimica</em> or <em>D. mim</em>. If the instructive hypothesis were correct, <em>D. mel</em> would form <em>D. mim</em>‘s grill-like mouthparts. Conversely, if McGinnis’ hypothesis were correct, <em>D. mel</em>‘s mouthparts should stay the same.</p>
<p>As McGinnis predicted, the flies with the <em>D. mim</em> genes did not develop <em>D. mim</em>’s grill-like features. There was one feature of <em>D. mim</em>’s, however, that did sneak through: Sensory organs called maxillary palps that usually stick out from the face for <em>D. mel</em> were instead aligned parallel to the mouth. This showed that the <em>pb</em> gene provided both a marker for where the mouth should form as well as instructions on how to form it. Though the main outcome favored McGinnis’ theory, both hypotheses were largely correct.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/431137/original/file-20211109-19-1g7uz6.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Side-by-side comparison of the mouthparts of the _D. mel_ and _D. mim_ fruit fly species." src="https://images.theconversation.com/files/431137/original/file-20211109-19-1g7uz6.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/431137/original/file-20211109-19-1g7uz6.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=212&fit=crop&dpr=1 600w, https://images.theconversation.com/files/431137/original/file-20211109-19-1g7uz6.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=212&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/431137/original/file-20211109-19-1g7uz6.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=212&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/431137/original/file-20211109-19-1g7uz6.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=266&fit=crop&dpr=1 754w, https://images.theconversation.com/files/431137/original/file-20211109-19-1g7uz6.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=266&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/431137/original/file-20211109-19-1g7uz6.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=266&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption"><em>D. mel</em> and <em>D. mim</em> have mouthparts, colored tan here, that look very different from each other.</span>
<span class="attribution"><a class="source" href="https://doi.org/10.1126/sciadv.abk1003">Ankush Auradkar</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<p>Auradkar also wondered how the <em>pb</em> gene determined the orientation of the maxillary palps. It could have done this by changing the protein it encodes, which carries out the instructions given by the gene. Or it could have changed how it controls other genes, acting like a light switch that determines when and where genes are turned on. Through more testing, he found that this <em>D. mim</em> feature resulted from changing how strongly the <em>pb</em> gene turns on in regions that form the palps, as opposed to changes in the protein itself. This finding highlights once again the remarkable preservation of Hox protein function over evolution – the genetic hardware worked as well in one species as the other. </p>
<p>Auradkar also found that Hox genes engage in an evolutionary tug-of-war with each other. One Hox gene may become more dominant than another and determine what features will ultimately form in a species.</p>
<p>These experiments showed that even subtle changes in how Hox genes interact with each other can have significant consequences for an organism’s body shape.</p>
<h2>Hox genes and human health</h2>
<p>What do these fly studies mean for people? </p>
<p>First, they provide a window into how the body plans of different species change over the course of evolution. Understanding how Hox genes can manipulate animal development to promote their survival could elucidate why animals look the way they do. Similar mechanisms could explain why humans no longer look like chimps.</p>
<p>Second, these insights may lead to a better understanding of how <a href="https://www.who.int/news-room/fact-sheets/detail/congenital-anomalies">congenital birth defects</a> arise in people. Changes, or mutations, that disrupt the normal functioning of Hox genes could result in conditions like cleft lip or congenital heart disease. New therapies on the horizon using CRISPR-based genome editing could be used to treat these often debilitating conditions, including <a href="https://doi.org/10.1126/science.aau1549">muscular dystrophy</a>.</p>
<p>[<em>Get the best of The Conversation, every weekend.</em> <a href="https://theconversation.com/us/newsletters/weekly-highlights-61?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=weeklybest">Sign up for our weekly newsletter</a>.]</p><img src="https://counter.theconversation.com/content/171456/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ethan Bier has equity interest in two companies he co-founded: Synbal Inc. and Agragene, Inc., which may potentially benefit from the research results. He also serves on Synbal's board of directors and the scientific advisory board for both companies.</span></em></p>Hox genes make sure all your body parts grow in the right place. Understanding how they work can reveal the process of evolution and lead to potential treatments for congenital birth defects.Ethan Bier, Professor of Cell and Developmental Biology, University of California, San DiegoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1689832021-09-30T13:53:12Z2021-09-30T13:53:12ZGene-edited crops: expert Q+A on what field trials could mean for the future of food<figure><img src="https://images.theconversation.com/files/424015/original/file-20210930-26-hsn3dx.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C7024%2C4510&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/agriculturist-utilize-core-data-network-internet-1884814591">Attasit Saentep/Shutterstock</a></span></figcaption></figure><p><em>Firmly outside the EU, where regulations are <a href="https://www.bbc.co.uk/news/science-environment-58711230">considered tighter</a>, the UK government plans to <a href="https://www.theguardian.com/environment/2021/sep/29/genetically-modified-food-a-step-closer-in-england-as-laws-relaxed">revise regulations</a> on <a href="https://theconversation.com/uk/topics/gene-editing-18986">gene editing</a> in agriculture in England, enabling field trials of crops which have had their DNA spliced to accentuate particular qualities, like resistance to disease or drought. This will be followed by a broader review of rules on genetically modified organisms.</em></p>
<p><em>The British public has traditionally been sceptical of genetically manipulating food, but should it be? What could new technology offer farming? And what are the risks? We asked professor of ecology at Southampton University, Guy Poppy.</em></p>
<p><strong>What actually is gene editing? How does it differ from genetic modification?</strong></p>
<p>Humans have been genetically modifying plants and animals ever since we stopped being hunter-gatherers. It’s just the way in which we modify the genes of an organism which has changed. </p>
<p>Random mutations occur in the DNA of organisms all the time. When a variation emerged in the past which a farmer happened to like, such as a tomato plant which produced juicier fruit, they were likely to breed that plant to ensure the trait was passed on. Repeating this process over generations created organisms with more of the characteristics people like. Human hands have directed evolution through this process of selective breeding since the dawn of agriculture.</p>
<p>Genetic modification (GM) typically involves inserting genes into the genome of a plant or animal. The outcome can be similar to selective breeding, but the results are more immediate and precise. Genetic modification can also create characteristics which would be unlikely through any form of selective breeding.</p>
<p>Take transgenic organisms. These are the products of transferring a gene from one organism’s genome to another, like a GM crop spliced with insecticidal proteins found in soil bacteria. </p>
<p>Gene editing (GE) is the result of more recent technology, such as CRISPR-Cas9, which can quickly, precisely and (relatively) cheaply edit parts of a genome by removing, altering or adding sections of DNA. Gene editing typically doesn’t involve introducing genes from other species, but these techniques allow quite complex control of an organism’s genome.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/what-is-crispr-the-gene-editing-technology-that-won-the-chemistry-nobel-prize-147695">What is CRISPR, the gene editing technology that won the Chemistry Nobel prize?</a>
</strong>
</em>
</p>
<hr>
<p>Gene editing can direct the evolution of plants and animals to yield varieties that would have taken conventional breeding many generations to produce. As a result, many countries are revising their regulations for genetically modified organisms (GMOs) to reflect the capabilities of this new technology, and in the case of the UK, when the technology is used to develop a crop which could not have been produced through conventional breeding.</p>
<p><strong>Could these field trials lead to the widespread use of gene-edited crops?</strong></p>
<p>No. The current proposals allow researchers or food firms to conduct field trials of gene-edited crops in England with the approval of the Department for Environment, Food and Rural Affairs (Defra). The costs and some of the barriers to starting research have been lifted, but we’re still waiting for new legislation which would govern the wider use of gene editing in the UK. Only then might we see the sale of gene-edited crops, which would be considered by the Food Standards agency.</p>
<figure class="align-center ">
<img alt="A collection of root vegetables." src="https://images.theconversation.com/files/423919/original/file-20210929-18-1pbnc98.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/423919/original/file-20210929-18-1pbnc98.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/423919/original/file-20210929-18-1pbnc98.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/423919/original/file-20210929-18-1pbnc98.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/423919/original/file-20210929-18-1pbnc98.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/423919/original/file-20210929-18-1pbnc98.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/423919/original/file-20210929-18-1pbnc98.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Gene-edited vegetables are still not likely to appear on supermarket shelves any time soon.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/root-crops-carrots-parsley-turnip-onion-750895588">Ulrich22/Shutterstock</a></span>
</figcaption>
</figure>
<p>Some may see Defra’s decision to allow research as approving gene-edited crops by the back door. Others might fear that it will lead to the wider consideration of all genetic technologies available for editing plants, animals and even humans. </p>
<p>A simpler approval process is likely to encourage more scientists to undertake field trials. </p>
<p><strong>What are some of the potential benefits of gene editing food crops?</strong></p>
<p>Gene editing can make plants and animals more nutritious or resilient to climate change, for example. Many plants contain anti-nutrients – substances which restrict the availability of nutrients to the human body during digestion. Gene editing could target and remove these, making the plant more nutritious.</p>
<p>Gene editing can also change a plant’s water requirements, producing crops that need less water to grow. In 2018, scientists discovered that by altering the expression of a gene that is found in all plants, they could make tobacco plants <a href="https://www.nature.com/articles/s41598-018-22431-5">25% more water-efficient</a>. Now they are testing this technique on food crops, like lettuce. The idea is to make crops more resilient to droughts, which are likely to become more frequent and severe in many growing regions as the world warms.</p>
<p>I have written before about <a href="https://www.nature.com/articles/d41586-020-02780-w">removing food allergens</a> with gene editing, by effectively silencing genes associated with allergens. <a href="https://www.ingateygen.com/">IngateyGen</a>, a biotechnology company based in the US has patented a process for making hypoallergenic peanut plants. The company hopes to produce other plants as part of a partnership with nearby Fayetteville State University. </p>
<p>Clearly, the future of gene editing could involve much more than just increasing crop yield or reducing the use of pesticides, but it needs to be developed thoughtfully. </p>
<p><strong>What worries do you have?</strong></p>
<p>The safety and environmental impact of GM foods is important, and there are well developed scientific processes to assess and manage these risks. I do fear the government is avoiding some of the real issues raised by gene editing but relevant to how we grow food in the future, such as the business models of current food producers and how affordable gene-edited food will be, particularly for the world’s poorest people.</p>
<p>I’m also concerned about issues which are somewhat hard to predict. Civilisation already relies on obtaining much of its calories from a few staple crops, which represent a fraction of 1% of the total biodiversity which exists. One criticism of GM technology is that it encourages the expansion of a few varieties of staple crops, otherwise known as cultivars. This narrows genetic variation between crop plants even further. A diverse genome is more resilient to pests, diseases and climate change. Repeatedly breeding just a handful of cultivars can lead to widescale crop failure, as occurred with <a href="https://www.newscientist.com/article/mg15120431-200-tomorrows-bitter-harvest-the-genetic-diversity-of-our-agriculture-is-rapidly-vanishing-leaving-our-crops-prone-to-pest-and-plague/">sugar cane</a> in the 1970s.</p>
<figure class="align-center ">
<img alt="A hand holds a green leaf covered in yellow spots." src="https://images.theconversation.com/files/424018/original/file-20210930-16-1sr23wj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/424018/original/file-20210930-16-1sr23wj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/424018/original/file-20210930-16-1sr23wj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/424018/original/file-20210930-16-1sr23wj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/424018/original/file-20210930-16-1sr23wj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/424018/original/file-20210930-16-1sr23wj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/424018/original/file-20210930-16-1sr23wj.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">
<figcaption>
<span class="caption">The genetic diversity of the world’s food is shrinking, leaving crop species prone to pests and disease.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/coffee-rust-diseased-plant-region-matagalpa-1838795902">Viola Hofmann/Shutterstock</a></span>
</figcaption>
</figure>
<p>Gene editing could make crop species more diverse if it could result in farmers using more species and cultivars, as gene-editing becomes more available and accepted. Because CRISPR has made this technology cheaper, gene editing could be used to improve the genomes of mutliple cultivars and many different crop species, injecting some diversity into farm fields. </p>
<p>But regulation of GM plants and animals is complex, expensive and increasingly seen as a barrier to innovation by both scientists and industry. If the regulation of gene-edited crops were made simpler, it could mean the editing of more crop species and cultivars. This would also diversify access to gene-edited products and the number of organisations with products on offer, preventing a few, large corporations from monopolising the process.</p>
<p><strong>What do you think could be the future of this technology?</strong></p>
<p>Too often in the past, people have heard about scientific revolutions which have failed to deliver. It takes more than clever technology for these things take off. That’s why I believe some of the bigger issues about food and farming need addressing. </p>
<p>Defra’s proposals are a proportionate way to move beyond the current system of regulations, while accepting that gene editing is different from the GM technology which developed transgenic organisms. It would be a great shame to waste this opportunity by mishandling the debate.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/should-we-genetically-edit-the-food-we-eat-we-asked-two-experts-162959">Should we genetically edit the food we eat? We asked two experts</a>
</strong>
</em>
</p>
<hr>
<p>Scientists enjoy an even greater level of respect and trust among the public as a result of the pandemic and the success of multiple vaccines, some of which are the products of genetic modification. The Oxford/AstraZeneca vaccine, for example, uses an adenovirus, a type of pathogen that causes a common cold, to serve as the vehicle for getting a genetic sequence into your cells. In effect, that adenovirus is a GMO. It’s important that we maintain this trust by engaging with the public about what science is trying to achieve and what we can and can’t say, without overpromising or cherry-picking evidence.</p>
<p>Feeding the world while improving human and planetary health is not easy and will require more than the odd tool in the farming toolbox. There needs to be a debate about food and farming which can tackle multiple issues, including gene editing. I accept that it’s important to consider gene editing on its own, but it is also part of a complex food system. Gene editing could help to feed the world in a changing climate, but this is only realistic if these wider issues are discussed and considered. Otherwise we will be sifting through claims and counter-claims, like during the GM debate of the 1990s and early 2000s, when two sects argued and argued rather than explore what people need from a food and farming system.</p><img src="https://counter.theconversation.com/content/168983/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Guy Poppy received funding from UKRI and is Director of the project 'transforming UK food systems for healthy people and a healthy environment'.</span></em></p>Field trials of genetically edited crop plants are to be allowed in England under new government proposals.Guy Poppy, Director of Multidisciplinary Research and Professor of Ecology, University of SouthamptonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1629592021-08-11T12:27:19Z2021-08-11T12:27:19ZShould we genetically edit the food we eat? We asked two experts<figure><img src="https://images.theconversation.com/files/409664/original/file-20210705-19-kw8reu.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/image-photo/pile-pumpkins-on-bale-straw-under-156566732">Michael Wick/Shutterstock.com</a></span></figcaption></figure><p><strong>Nicola Patron</strong>: Oil from soybeans gene-edited to produce a <a href="https://www.proactiveinvestors.com/companies/news/918560/calyxt-debuts-premium-soybean-cooking-oil-calyno-918560.html">“high oleic” oil</a> with no trans fats and less saturated fat is already on sale in the United States. Other products including <a href="https://www.cellectis.com/en/press/cellectis-plant-sciences-inc.-publishes-a-study-demonstrating-reduced-acrylamide-in-fried-potatoes">low-acrylamide potatoes</a> and <a href="http://pgandp.org/page475645.html">non-browning mushrooms</a> are expected to be launched in the near future. </p>
<p>The work I do might lead to similar products. I’m a molecular and synthetic plant biologist at the <a href="https://www.earlham.ac.uk">Earlham Institute</a>. My lab works to understand how plants control when and why genes are expressed as well as how they make certain chemicals. We aim to identify variants of genes that help plants to grow and to find and produce natural products like pheromones that are useful in agriculture or anti-cancer compounds used in chemotherapies. We also work to improve plant biotechnologies and have contributed to proof-of-concept studies demonstrating that genome editing can be used to develop useful traits in <a href="https://genomebiology.biomedcentral.com/articles/10.1186/s13059-015-0826-7">barley, brassica</a> and <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/pbi.13137">potatoes</a> by deleting just a few letters of DNA.</p>
<p><strong>Catherine Price</strong>: It’s great to be able to talk to a scientist working in this field, because GM crops have long been a very contentious issue, and for good reason. My work focuses on the social science aspects of the GM debate. I’m a sociologist based at a <a href="https://research.reading.ac.uk/change-in-agriculture/">research group</a> at the University of Reading looking at the future of agriculture. In <a href="http://wrap.warwick.ac.uk/133445/">previous work</a> I’ve examined how GM food is discussed by the media, so I have a good sense of how the state, NGOs, farmers, and citizens all view the science of GM foods – and it varies quite a bit. </p>
<p>So what exactly is the difference between GM and gene editing? I’ve come across many definitions in my time working on this topic.</p>
<p><strong>NP</strong>: I’m not surprised! There isn’t really an accepted definition of what genetic modification is, and that has certainly caused some problems. One could argue that the genetics of anything that’s been manipulated by humans has been modified in some way. We’ve been changing plant genomes for thousands of years. The process of domesticating and breeding crops made substantial changes to the sequences and structures of their genomes.</p>
<figure class="align-center ">
<img alt="Medieval calendar showing monthly agricultural tasks." src="https://images.theconversation.com/files/408868/original/file-20210629-26-1ysaca.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/408868/original/file-20210629-26-1ysaca.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=519&fit=crop&dpr=1 600w, https://images.theconversation.com/files/408868/original/file-20210629-26-1ysaca.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=519&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/408868/original/file-20210629-26-1ysaca.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=519&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/408868/original/file-20210629-26-1ysaca.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=652&fit=crop&dpr=1 754w, https://images.theconversation.com/files/408868/original/file-20210629-26-1ysaca.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=652&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/408868/original/file-20210629-26-1ysaca.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=652&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Agricultural calendar, c. 1306. As long as humanity has been farming, we’ve been altering the genetic make-up of crops.</span>
<span class="attribution"><a class="source" href="https://en.wikipedia.org/wiki/File:Crescenzi_calendar.jpg">Condé Museum</a></span>
</figcaption>
</figure>
<p>Since the 1980s, we’ve had the ability to use recombinant DNA technologies to insert DNA sequences into plant genomes in order to confer useful traits, such as resistance to insect pests. This could be a DNA sequence from a different individual of the same species, from a closely related species, or from a more distantly related species. Such crops became known as genetically modified organisms (GMOs). They first came on to the markets in the 1990s and are now widely grown on about <a href="https://royalsociety.org/topics-policy/projects/gm-plants/what-gm-crops-are-currently-being-grown-and-where/">10%</a> of agricultural land worldwide in <a href="https://www.isaaa.org/resources/publications/briefs/55/">29 countries</a>.</p>
<p>The outcomes of gene editing are quite different to those of GM. What genome editing technologies allow you to do is to make really precise changes to the DNA that already exists in an organism. You can delete something, even changing or deleting just one specific letter of the DNA code, or you can recode a longer section of a sequence. You can also use these technologies to insert DNA, but instead of inserting the new DNA randomly as happens with older GM technologies, you can insert it into a specific location in the genome.</p>
<hr>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/415651/original/file-20210811-17-zc3x6m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/415651/original/file-20210811-17-zc3x6m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/415651/original/file-20210811-17-zc3x6m.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/415651/original/file-20210811-17-zc3x6m.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/415651/original/file-20210811-17-zc3x6m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/415651/original/file-20210811-17-zc3x6m.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/415651/original/file-20210811-17-zc3x6m.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
</figcaption>
</figure>
<p><strong><em>This is a Head to Head story</em></strong></p>
<p><br><em>The Conversation’s <a href="https://theconversation.com/uk/topics/head-to-head-62019">Head to Head</a> articles feature academics from different disciplines chewing over current debates. If there’s a specific topic or question you’d like experts from different disciplines to discuss, please <a href="mailto:insights@theconversation.com">email us your question</a>.</em> </p>
<hr>
<p>Broadly, genetic modification has come to mean that one or more genes have been inserted whereas genome editing has come to mean small and specific changes to existing DNA.</p>
<h2>‘Frankenfood’</h2>
<p><strong>CP:</strong> You’ve just explained the science really clearly. And I think that might be what we’re missing in terms of the public debate – where often the loudest sentiment is that these technologies are unnatural or dangerous.</p>
<p>In previous work I’ve <a href="https://www.researchgate.net/profile/Catherine-Price-9/publication/310456988_Genetic_Futures_and_the_Media/links/5bb5f430299bf13e605e29db/Genetic-Futures-and-the-Media.pdf">analysed</a> how journalists frame genetics news. Journalists often liken the rearrangement and changes to genes to Frankenstein and the idea of runaway science. This is turn can invoke the idea that scientific progress interferes with nature, producing results which are unpredictable and ethically wrong.</p>
<figure class="align-center ">
<img alt="White mushrooms on wooden background." src="https://images.theconversation.com/files/408882/original/file-20210629-20-17w90x4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/408882/original/file-20210629-20-17w90x4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/408882/original/file-20210629-20-17w90x4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/408882/original/file-20210629-20-17w90x4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/408882/original/file-20210629-20-17w90x4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/408882/original/file-20210629-20-17w90x4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/408882/original/file-20210629-20-17w90x4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The common white button mushroom was genetically modified with the gene-editing tool CRISPR–Cas9 to resist browning. It was the first such organism to receive a green light from the US government.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/fresh-mushrooms-on-wooden-background-82617856">Valerii Evlakhov/Shutterstock</a></span>
</figcaption>
</figure>
<p>In 2015, for example, these <a href="https://doi.org/10.1191/14744744004eu301oa">Frankenfood headlines</a> dominated. There were a lot of people who were for it too, but I got the overall sense that it was deemed a risk and that part of the problem was that scientists didn’t try hard enough to explain the technical stuff and the risks, and that the public’s concerns weren’t being listened to. I think sometimes we treat the public as being stupid. If the science isn’t explained and the public aren’t consulted, what are they supposed to think?</p>
<p>In the UK, the gene-editing debate has sparked again. When Boris Johnson came into power, he stood on the steps of Downing Street <a href="https://www.business-live.co.uk/economic-development/boris-johnsons-message-business-satellites-16640138">and said</a> he wanted to enable gene edited and genetically modified crops. This led to a <a href="https://consult.defra.gov.uk/agri-food-chain-directorate/the-regulation-of-genetic-technologies/">government consultation</a> on the matter. The proposed changes – yet to be announced formally – <a href="https://www.wired.co.uk/article/uk-gmo-crops">define gene-edited organisms</a> as those “possessing genetic changes which could have been introduced by traditional breeding”. </p>
<p>But has the dominant view changed since 2015? It’s not clear. There are also concerns that weakened regulations will lock the UK into <a href="https://sustainablefoodtrust.org/articles/uk-gene-editing-consultation-say-no-to-deregulation/">industrialised farming methods</a>. And there’s no real sense of how gene edited or GM crops fit into the broader food system. Agriculture does not operate and exist in isolation.</p>
<p><strong>NP:</strong> I totally agree that there was insufficient communication in the past. People do understand the science if it is explained in a considered way. One thing I have found is that it’s important for people to understand that <em>all</em> crop breeding techniques involve rearrangements and changes to genes. The risks of using these new breeding technologies are no greater than for older breeding technologies, the products of which are subject to far fewer checks. For the most part, what domestication and plant breeding <a href="https://www.npr.org/sections/thesalt/2019/06/13/732160949/how-almonds-went-from-deadly-to-delicious">has achieved</a> is to <a href="https://science.sciencemag.org/content/364/6445/1095">remove toxins</a> and to make them more <a href="https://academic.oup.com/plcell/article/23/5/tpc.111.tt0511/6097094">nutritious and more high yielding</a>.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"734662715826962432"}"></div></p>
<p>In the summer of 2018, the European court of justice <a href="https://www.nature.com/articles/d41586-018-05814-6">ruled</a> that genome edited plants would also be classified as being genetically modified. But, if a plant was mutated using radiation or mutagenic chemicals, even if the results were exactly the same (or had even more changes), the plant would not be GM. To many, this <a href="https://www.nature.com/articles/nbt.4252">doesn’t make much sense</a>. When there are no new genes inserted, I struggle to understand how and why plants mutated with these technologies should be regulated in a different way. That’s why <a href="https://www.mpg.de/13748566/position-paper-crispr.pdf">European law in this area is controversial</a>.</p>
<p>Now with the UK being able to divert from European law post-Brexit, there is a discussion of whether that’s something that the country wants to keep. This is particularly relevant if the UK wants its agricultural products <a href="https://www.thetimes.co.uk/article/brexit-leaving-eu-will-give-freedom-to-grow-more-gm-crops-2fbdwl5b6">to be competitive</a> on the wider global market with products from the United States and Canada and Brazil and Australia, who have decided <a href="https://www.frontiersin.org/articles/10.3389/fpls.2020.586027/full">not to regulate</a> genome edited products in the same way that they do genetically modified products.</p>
<p><strong>CP:</strong> It’s the rearrangements and changes to genes which the media often pick up on. And this is where the idea of Frankenstein food gets brought into debates about GM foods. I think this illustrates why scientists need to communicate the risks rather than leaving it to journalists. The public are likely to have a <a href="https://doi.org/10.1177/0963662513518154">better understanding</a> then. </p>
<h2>The case for editing</h2>
<p><strong>NP:</strong> Genetic rearrangements and changes to the sequences of genes occur naturally <a href="https://cordis.europa.eu/article/id/31626-research-reveals-rapid-mutation-rate-of-plant-genomes">all the time</a>. They also occur with <a href="https://link.springer.com/chapter/10.1007/978-4-431-55675-6_9">older and established breeding technologies</a>. Applying genetic technologies to crop breeding makes the process of bringing combinations of beneficial sequences and genes together into the same plant easier. Because scientists know what changes are being made, the consequences of these changes are closely observed and extensively analysed even before the plants enter large-scale breeding programmes. The outcomes of gene editing are therefore more likely to be predictable.</p>
<p>I think what is critically important is for scientists to explain what we’re trying to achieve and the type of products we’re able to make – why they will be beneficial, both to health and the environment. </p>
<p>We’re using an <a href="http://www.fao.org/land-water/news-archive/news-detail/en/c/267297/">incredible amount</a> of <a href="http://www.fao.org/sustainability/news/detail/en/c/1274219/">land</a> and <a href="https://www.worldbank.org/en/topic/water-in-agriculture">water</a> for agriculture. And that often means that we are destroying pristine biodiverse environments, such as the Amazon rainforest, grasslands, wetlands and marshlands to grow more crops. Increasing yield on productive land and decreasing the amount of land used for agriculture is possibly the greatest impact that we will have on preserving biodiversity. Improving crop genetics can also reduce the amount of fertilisers and pesticides that we need to use, and we can make crops healthier, and increase their nutritional content.</p>
<p>A single change to one letter of DNA sequence can turn off a gene and have a substantial effect. For example, making a single mutation to inactivate two genes involved in <a href="https://www.forbes.com/sites/jennysplitter/2019/03/05/trans-fat-free-gene-edited-soybean-oil/?sh=27652c5f4c91">fatty acid biosynthesis</a> can lead to a different oil profile in oil seed crops making them healthier to consume. Plants also have genes that make them resistant or susceptible to specific diseases – a mutation in the coding sequence or in the regulatory sequences of these genes can mean that those pathogens <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/pbi.12677">can no longer infect them</a>, which can reduce the need for fungicides and other chemicals.</p>
<p>Scientific analyses that have been done on the impacts of many biotech crops have <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/ajae.12162">identified many benefits</a>, including reducing the use of pesticides and improving the welfare and health of subsistence farmers.</p>
<p>I think it’s really important that people understand that even when the goal is to increase yields, crop improvement is not only about profit. </p>
<h2>Power in the seed system</h2>
<p><strong>CP:</strong> I’d certainly agree with you that these are very pressing issues and that the technology has the potential to do a lot of good, especially considering climate change and biodiversity loss. But what you say about profit can’t really be ignored. The dominance of the big companies is a big problem. I think that’s what’s underlying the issues now actually. People are asking: <a href="http://seedcontrol.eu/seed-stories.php">who’s got power in the seed system</a>? Who’s controlling our food system? What was the big six is now the <a href="https://european-seed.com/2019/02/from-big-six-to-big-four-new-oecd-study-sheds-light-on-concentration-and-competition-in-seed-markets/">big four</a> after a series of mergers (DowDuPont, Bayer-Monsanto, BASF and ChemChina-Syngenta); they’re controlling like <a href="https://civileats.com/2019/01/11/the-sobering-details-behind-the-latest-seed-monopoly-chart/">60%</a> of the <a href="https://theconversation.com/how-gardeners-are-reclaiming-agriculture-from-industry-one-seed-at-a-time-128071">seed supply</a>, you know?</p>
<p>Yes, these companies do invest huge amounts of capital and time developing innovations such as gene-edited crops. So of course they protect these innovations through patents and intellectual property rights. But for many farmers in developing countries, these patents dispossess them of their rights to <a href="https://www.theguardian.com/environment/2013/feb/12/monsanto-sues-farmers-seed-patents">save seeds</a>. Instead of saving seed and planting it the following year, farmers have to purchase new seed. This is arguably linked to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5427059/">horrific stories</a> in some parts of the world – such as farmers accumulating so much debt that they take their own lives. There’s also the question of whether it is ethically correct for companies to own life. </p>
<figure class="align-center ">
<img alt="A hand cupping seeds; seed packets in background." src="https://images.theconversation.com/files/408886/original/file-20210629-24-lcn6gi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/408886/original/file-20210629-24-lcn6gi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/408886/original/file-20210629-24-lcn6gi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/408886/original/file-20210629-24-lcn6gi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/408886/original/file-20210629-24-lcn6gi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/408886/original/file-20210629-24-lcn6gi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/408886/original/file-20210629-24-lcn6gi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The traditional practice of seed saving is illegal under the terms of many seed companies.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/united-kingdom-january-25-2012-woman-196672658">Caron Badkin/Shutterstock.com</a></span>
</figcaption>
</figure>
<p><strong>NP:</strong> I agree that ownership of the technologies underlying food production should be questioned and openly debated. I have <a href="https://www.synbioleap.org/strategic-action-plans-blog/2017/2/27/feeding-the-future-the-case-for-open-source-technology-and-an-inclusive-plant-bioengineering-community">previously written</a> about the negative consequences of some of the patenting and ownership practices used in plant biotechnology. However, while a few companies may sell the majority of proprietary seeds, their dominance over global food supply chains is overstated. Smallholder farmers, who generally do not grow proprietary seeds, <a href="https://www.globalagriculture.org/whats-new/news/en/32345.html">produce more than half of global food</a>. </p>
<p>One of the issues that often comes up as a concern is that <a href="http://sbc.ucdavis.edu/Biotech_for_Sustain_pages/Herbicide_Tolerance/">specific herbicides must be used</a> in conjunction with herbicide-tolerant GM plants. Until the patents of these herbicides <a href="https://www.technologyreview.com/2015/07/30/166919/as-patents-expire-farmers-plant-generic-gmos/">expire</a>, growers need to purchase both seeds and herbicides from the same company. Further, some of these crops are developed by chemical companies with a problematic history including the use of damaging chemicals such as <a href="https://www.theguardian.com/environment/2012/feb/24/monsanto-agent-orange-west-virginia">Agent Orange</a>. It’s undoubtedly tricky asking people to trust seed produced by these companies.</p>
<p>Bad behaviour and poor corporate responsibility by companies should unquestionably be called out, curtailed and, where necessary, regulated. But seeking to counter the behaviour of a few companies by suppressing the use of technologies with enormous potential that are being used in public development programmes to <a href="https://www.isaaa.org/resources/publications/briefs/47/download/isaaa-brief-47-2014.pdf">improve lives</a> does not seem reasonable to me. I argue that we should instead confront questions of ownership, and facilitate global access to enabling technologies to promote locally-led solutions. </p>
<h2>What do most people think?</h2>
<p><strong>CP:</strong> That is certainly where lots of the push back comes from. I think even the smaller companies that are developing are always going to be associated with that. And yes, it’s time we debated that – the food system and the money seems to be a lot of the problem, not the science itself. </p>
<p>Having said that, I don’t think the reason gene editing crops are important is coming through at the moment. I agree that these crops are important for biodiversity and the need to produce more food on less land with less water. But sometimes there’s a sense that these things are being forced on people. </p>
<p>Mexicans actually <a href="https://www.nature.com/articles/511016a">pushed back on GM maize</a> because maize is so culturally important to them. Soon after GM maize was introduced, in the late 1990s, they <a href="https://www.nature.com/articles/35107068">found genetic sequences</a> known to be present in the GM varieties in a few samples of crops raised from local varieties. There was a sense then of an imposition or attack on their culture. And as a result of the aftermath of that debate Mexico actually ruled out GM maize in order to protect its maize breeding programmes, although it did continue to grow GM cotton.</p>
<figure class="align-center ">
<img alt="Man holds stack of different coloured corn on the cob." src="https://images.theconversation.com/files/408888/original/file-20210629-26-1sok1k4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/408888/original/file-20210629-26-1sok1k4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/408888/original/file-20210629-26-1sok1k4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/408888/original/file-20210629-26-1sok1k4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/408888/original/file-20210629-26-1sok1k4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/408888/original/file-20210629-26-1sok1k4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/408888/original/file-20210629-26-1sok1k4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Mexico has an extraordinary diversity of maize – which was felt to be under threat from GM maize.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/mexican-corn-maize-dried-blue-cobs-1479684842">Marcos Castillo/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>That shows that sometimes we need to work with people more. We need to explain the science and the benefits and ask what they think, rather than framing it in a way that makes it seem like it’s inevitable. Yes, the possible benefits are enormous, but the people who are deciding which benefits are chosen and how, are often governments and corporations rather than farmers and the local people. And that’s a problem. The UK government, for example, often focuses on <a href="https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/293037/10-669-gcsa-guidelines-scientific-engineering-advice-policy-making.pdf">scientific advice</a> in policy-making but I don’t think that’s the right route to go down. You need a wider debate sometimes as to what society wants, especially considering just how powerful these big companies are in the food system.</p>
<p>The recent consultation is an example of this. There was a sense that the government had <a href="https://www.foodethicscouncil.org/resource/open-letter-re-weakening-regulation-on-genetic-engineering/">already decided</a> that gene editing is going to happen, both on plants and animals. The consultation was made quite technical – too technical for people without a scientific understanding to contribute to. A lot of important questions – such as whether people consider gene editing to be ethical or who they believe will benefit from these technologies – just weren’t asked.</p>
<p>It’s not always about science. A lot of people are actually quite accepting of the science, as we’ve discussed – the problem is who is controlling the food system.</p>
<p><strong>NP</strong>: I share people’s concerns about the lack of diversity in the seed trading companies. Perhaps ironically, I think that one of the reasons that there are so few agrotech companies is partly a result of the regulatory burdens around GM. It has been estimated to cost upwards of <a href="https://www.isaaa.org/kc/cropbiotechupdate/article/default.asp?ID=14638">a hundred million dollars</a> to bring a GM crop to market, with a substantial fraction spent on the regulatory process,</p>
<p>There was considerable diversity in the plant biotechnology IP [intellectual property] landscape, with quite a lot of it owned by universities. However, it has been argued that the <a href="https://www.nature.com/articles/nbt.3393">strategic use of patent rights</a> and the implementation of high and scientifically unjustified <a href="https://core.ac.uk/download/pdf/76797108.pdf">regulatory barriers</a> stifled innovation in smaller companies leaving only very large companies with the resources necessary to bring products to market. In recent years, with new patent and regulatory landscapes of genome editing, we see new plant biotech companies <a href="https://www.nature.com/articles/d41587-019-00027-2">beginning to emerge</a>.</p>
<p>One of the things I’ve been involved in is enabling <a href="https://www.openplant.org">open-source plant biotechnology</a> and accelerating technology transfer with the aim of enabling entrepreneurship and empowering scientists in resource poor regions. The long-term goal is to help scientists who are closely connected to the needs of their local farmers and populations obtain access to the training and technologies they need to start local companies, develop local crop varieties, and help democratise the seed production system.</p>
<p><strong>CP</strong>: I would agree. There’s a lot of government money being pushed into science the technology. But I think the way the government carried out the recent consultation – that sense of asking what people wanted, but not actually wanting to know the answer – might set the debate back a bit, at least in the UK. I think if the consultation had been done a bit differently, you might’ve got a better conversation going.</p>
<p>They might, for example, have involved a <a href="https://esrc.ukri.org/public-engagement/public-engagement-guidance/guide-to-public-engagement/choosing-your-activities/citizens-jury/">citizen jury</a> or similar. This is such an important topic, and it’s key that the public feel consulted. Then people could ask an expert – someone like you – what about this? What about that? Then the government would also have more of an understanding of the nature of public concerns and interest – and realise perhaps that they relate predominantly to the business or social side of things, rather than purely the science.</p><img src="https://counter.theconversation.com/content/162959/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Nicola Patron receives funding from the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation (UKRI).</span></em></p><p class="fine-print"><em><span>Catherine Price receives funding from the British Academy. </span></em></p>Catherine Price, sociologist, and Nicola Patron, synthetic plant biologist, discuss the promises, dangers and concerns around gene edited and GM crops.Nicola Patron, Synthetic Biology Group Leader, Earlham InstituteCatherine Price, Postdoctoral Researcher, Change in Agriculture, University of ReadingLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1644592021-08-05T12:48:25Z2021-08-05T12:48:25ZFrom CRISPR to glowing proteins to optogenetics – scientists’ most powerful technologies have been borrowed from nature<figure><img src="https://images.theconversation.com/files/414624/original/file-20210804-15-1fuewod.jpg?ixlib=rb-1.1.0&rect=391%2C30%2C3002%2C1822&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Crystal jellyfish contain glowing proteins that scientists repurpose for an endless array of studies.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/crystal-jellyfish-royalty-free-image/1013185852?adppopup=true">Weili Li/Moment via Getty Images</a></span></figcaption></figure><p><a href="https://www.nature.com/scitable/topicpage/discovery-of-dna-structure-and-function-watson-397/">Watson and Crick</a>, <a href="https://www.nobelprize.org/prizes/physics/1933/schrodinger/biographical/">Schrödinger</a> and <a href="https://www.nobelprize.org/prizes/physics/1921/einstein/biographical/">Einstein</a> all made theoretical breakthroughs that have changed the world’s understanding of science. </p>
<p>Today big, game-changing ideas are less common. New and improved techniques are the <a href="https://doi.org/10.1038/nmeth1004-1">driving force behind modern scientific research and discoveries</a>. They allow scientists – <a href="https://scholar.google.com/citations?user=RpiSPiwAAAAJ&hl=en&oi=ao">including chemists like me</a> – to do our experiments faster than before, and they shine light on areas of science hidden to our predecessors. </p>
<p>Three cutting-edge techniques – the gene-editing tool <a href="https://www.newscientist.com/definition/what-is-crispr/">CRISPR</a>, <a href="https://doi.org/10.1242/jcs.072744">fluorescent proteins</a> and <a href="https://www.scientificamerican.com/article/optogenetics-controlling/">optogenetics</a> – were all inspired by nature. Biomolecular tools that have worked for bacteria, jellyfish and algae for millions of years are now being used in medicine and biological research. Directly or indirectly, they will change the lives of everyday people.</p>
<h2>Bacterial defense systems as genetic editors</h2>
<p>Bacteria and viruses battle themselves and one another. They are at constant biochemical war, <a href="https://doi.org/10.1016/j.cub.2019.04.024">competing for scarce resources</a>. </p>
<p>One of the weapons that bacteria have in their arsenal is the <a href="https://www.livescience.com/58790-crispr-explained.html">CRISPR-Cas system</a>. It is a genetic library consisting of short repeats of DNA gathered over time from hostile viruses, paired with a protein called Cas that can cut viral DNA as if with scissors. In the natural world, when bacteria are attacked by viruses whose DNA has been stored in the CRISPR archive, the CRISPR-Cas system hunts down, cuts and destroys the viral DNA.</p>
<p>Scientists have repurposed these weapons for their own use, with groundbreaking effect. Jennifer Doudna, a biochemist based at the University of California, Berkeley, and French microbiologist Emmanuelle Charpentier shared the <a href="https://theconversation.com/nobel-prize-for-chemistry-honors-exquisitely-precise-gene-editing-technique-crispr-a-gene-engineer-explains-how-it-works-147701">2020 Nobel Prize in chemistry</a> for <a href="https://www.nobelprize.org/prizes/chemistry/2020/doudna/lecture/">the development of</a> <a href="https://theconversation.com/nobel-prize-for-crispr-honors-two-great-scientists-and-leaves-out-many-others-147730">CRISPR-Cas as a gene-editing technique</a>. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/414580/original/file-20210804-21-1k8hfpd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="French researcher Emmanuelle Charpentier (left) and U.S. biochemist Jennifer Doudna (right)" src="https://images.theconversation.com/files/414580/original/file-20210804-21-1k8hfpd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/414580/original/file-20210804-21-1k8hfpd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=365&fit=crop&dpr=1 600w, https://images.theconversation.com/files/414580/original/file-20210804-21-1k8hfpd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=365&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/414580/original/file-20210804-21-1k8hfpd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=365&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/414580/original/file-20210804-21-1k8hfpd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=459&fit=crop&dpr=1 754w, https://images.theconversation.com/files/414580/original/file-20210804-21-1k8hfpd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=459&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/414580/original/file-20210804-21-1k8hfpd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=459&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">French microbiologist Emmanuelle Charpentier (left) and U.S. biochemist Jennifer Doudna shared the 2020 Nobel Prize in Chemistry for development of the CRISPR-Cas gene editing technique.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/french-researcher-in-microbiology-genetics-and-biochemistry-news-photo/493945408?adppopup=true">Miguel Riopa/AFP via Getty Images</a></span>
</figcaption>
</figure>
<p>The <a href="https://www.genome.gov/human-genome-project">Human Genome Project</a> has provided a nearly complete genetic sequence for humans and given scientists a template to sequence all other organisms. However, before CRISPR-Cas, we researchers didn’t have the tools to easily access and edit the genes in living organisms. Today, thanks to CRISPR-Cas, lab work that used to take months and years and cost hundreds of thousands of dollars can be done in less than a week for just a few hundred dollars. </p>
<p>There are more than 10,000 genetic disorders caused by mutations that occur on only one gene, the <a href="http://hihg.med.miami.edu/thromboticstorm/genetics-overview/single-gene-disorders">so-called single-gene disorders</a>. They affect millions of people. <a href="https://www.genome.gov/Genetic-Disorders/Sickle-Cell-Disease">Sickle cell anemia</a>, <a href="https://www.cff.org/What-is-CF/Genetics/CF-Genetics-The-Basics/">cystic fibrosis</a> and <a href="https://doi.org/10.31887/DCNS.2016.18.1/pnopoulos">Huntington’s disease</a> are among the most well-known of these disorders. These are all obvious targets for CRISPR therapy because it is much simpler to fix or replace just one defective gene rather than needing to correct errors on multiple genes. </p>
<p>For example, in preclinical studies, <a href="https://doi.org/10.1056/NEJMoa2107454">researchers injected</a> an encapsuled CRISPR system into patients born with a rare genetic disease, <a href="https://rarediseases.info.nih.gov/diseases/656/familial-transthyretin-amyloidosis">transthyretin amyloidosis</a>, that causes fatal nerve and heart conditions. Preliminary results from the study demonstrated <a href="https://www.nature.com/articles/d41586-021-01776-4">that CRISPR-Cas can be injected</a> directly into patients in such a way that it can find and edit the faulty genes associated with a disease. In the six patients included in this landmark work, the encapsuled CRISPR-Cas minimissiles reached their target genes and did their job, causing a significant drop in a <a href="https://www.nature.com/scitable/topicpage/protein-misfolding-and-degenerative-diseases-14434929/">misfolded protein</a> associated with the disease. </p>
<h2>Jellyfish light up the microscopic world</h2>
<p>The <a href="https://faculty.washington.edu/cemills/Aequorea.html">crystal jellyfish, <em>Aequorea victoria</em></a>, which drifts aimlessly in the northern Pacific, has no brain, no anus and no poisonous stingers. It is an unlikely candidate to ignite a revolution in biotechnology. Yet on the periphery of its umbrella, it has about 300 photo-organs that give off pinpricks of green light that have changed the way science is conducted.</p>
<p>This bioluminescent light in the jellyfish stems from a luminescent protein called aequorin and a fluorescent molecule called <a href="https://doi.org/10.1242/jcs.072744">green fluorescent protein</a>, or GFP. In modern biotechnology GFP acts as a molecular lightbulb that can be fused to other proteins, allowing researchers to track them and to see when and where proteins are being made in the cells of living organisms. Fluorescent protein technology is used in thousands of labs every day and has resulted in the awarding of two Nobel Prizes, <a href="https://www.nobelprize.org/prizes/chemistry/2008/popular-information/">one in 2008</a> and the <a href="https://www.nobelprize.org/prizes/chemistry/2014/summary/">other in 2014</a>. And fluorescent proteins have now been found in <a href="https://doi.org/10.1242/jcs.072744">many more species</a>. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/414422/original/file-20210803-13-vphczn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Fluorescent bacteria in petri dish and test tube" src="https://images.theconversation.com/files/414422/original/file-20210803-13-vphczn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/414422/original/file-20210803-13-vphczn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/414422/original/file-20210803-13-vphczn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/414422/original/file-20210803-13-vphczn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/414422/original/file-20210803-13-vphczn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/414422/original/file-20210803-13-vphczn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/414422/original/file-20210803-13-vphczn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Fluorescent proteins, shown here glowing inside <em>E. coli</em> bacteria, allow researchers to visualize biological structures and processes.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/red-and-green-fluorescent-proteins-in-escherichia-royalty-free-image/124368916?adppopup=true">Fernan Federici/Moment via Getty Images</a></span>
</figcaption>
</figure>
<p>This technology proved its utility once again when researchers created genetically modified <a href="https://doi.org/10.1016/j.cell.2020.05.042">COVID-19 viruses that express GFP</a>. The resulting fluorescence makes it possible to follow the path of the viruses as they enter the respiratory system and bind to surface cells with hairlike structures. </p>
<h2>Algae let us play the brain neuron by neuron</h2>
<p>When algae, which depend on sunlight for growth, are placed in a large aquarium in a darkened room, they swim around aimlessly. But if a lamp is turned on, the algae will swim toward the light. The single-celled <a href="https://www.britannica.com/science/flagellate">flagellates</a> – so named for the whiplike appendages they use to move around – don’t have eyes. Instead, they have a structure called an eyespot that distinguishes between light and darkness. The eyespot is studded with <a href="https://doi.org/10.1073/pnas.1525538113">light-sensitive proteins called channelrhodopsins</a>. </p>
<p>In the early 2000s, <a href="https://doi.org/10.1038/nn1525">researchers discovered</a> that when they genetically inserted these channelrhodopsins into the nerve cells of any organism, illuminating the channelrhodopsins with blue light caused neurons to fire. This technique, known as optogenetics, involves inserting the algae gene that makes channelrhodopsin into neurons. When a pinpoint beam of blue light is shined on these neurons, the channelrhodopsins open up, calcium ions flood through the neurons and the neurons fire. </p>
<p>Using this tool, scientists can stimulate groups of neurons selectively and repeatedly, thereby gaining a more precise understanding of which neurons to target to treat specific disorders and diseases. Optogenetics might hold the key to treating debilitating and deadly brain diseases, such as Alzheimer’s and Parkinson’s. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/414426/original/file-20210803-25-1p9rv2y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Illustration of amyloid plaque buildup on cells" src="https://images.theconversation.com/files/414426/original/file-20210803-25-1p9rv2y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/414426/original/file-20210803-25-1p9rv2y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/414426/original/file-20210803-25-1p9rv2y.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/414426/original/file-20210803-25-1p9rv2y.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/414426/original/file-20210803-25-1p9rv2y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/414426/original/file-20210803-25-1p9rv2y.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/414426/original/file-20210803-25-1p9rv2y.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Optogenetics could help treat Alzheimer’s disease, which is characterized by the buildup of misfolded proteins called amyloid plaques.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/illustration-of-alzheimers-disease-royalty-free-illustration/1124681623?adppopup=true">Sciepro/Science Photo Library via Getty Images</a></span>
</figcaption>
</figure>
<p>But optogenetics isn’t only useful for understanding the brain. Researchers have used optogenetic techniques <a href="https://doi.org/10.1038/s41591-021-01351-4">to partially reverse blindness</a> and have found promising results in clinical trials using optogenetics on patients with <a href="https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/retinitis-pigmentosa">retinitis pigmentosa</a>, a group of genetic disorders that break down retinal cells. And in mouse studies, the technique has been used to <a href="https://doi.org/10.1016/j.pbiomolbio.2019.08.013">manipulate heartbeat</a> and <a href="https://doi.org/10.1016/j.autneu.2020.102733">regulate bowel movements of constipated mice</a>. </p>
<h2>What else lies within nature’s toolbox?</h2>
<p>What undiscovered techniques does nature still hold for us? </p>
<p>According to <a href="https://doi.org/10.1073/pnas.1711842115">a 2018 study</a>, people represent just 0.01% of all living things by mass but have caused the loss of 83% of all wild mammals and half of all plants in our brief time on Earth. By annihilating nature, humankind might be losing out on new, powerful and life-altering techniques without having even imagined them.</p>
<p>[<em>Over 100,000 readers rely on The Conversation’s newsletter to understand the world.</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=100Ksignup">Sign up today</a>.]</p>
<p>After all, no one could have foreseen that the discovery of three groundbreaking processes derived from nature could change the way science is done.</p><img src="https://counter.theconversation.com/content/164459/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Marc Zimmer received funding from NIH for his fluorescent protein research. </span></em></p>Three pioneering technologies have forever altered how researchers do their work and promise to revolutionize medicine, from correcting genetic disorders to treating degenerative brain diseases.Marc Zimmer, Professor of Chemistry, Connecticut CollegeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1634722021-07-19T12:07:04Z2021-07-19T12:07:04ZBioweapons research is banned by an international treaty – but nobody is checking for violations<figure><img src="https://images.theconversation.com/files/410440/original/file-20210708-15-1j917yr.jpg?ixlib=rb-1.1.0&rect=7%2C7%2C985%2C655&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A global treaty bans research or stockpiling of biological weapons — but allows bioweapon defense planning.</span> <span class="attribution"><a class="source" href="https://www.dvidshub.net/image/169940/technician-course-prepares-chemical-biological-radiological-and-nuclear-uncertainty">US Dept. of Defense via DVIDS</a></span></figcaption></figure><p>Scientists are making dramatic progress with techniques for “gene splicing” – modifying the genetic makeup of organisms. </p>
<p>This work includes bioengineering pathogens for medical research, techniques that also can be used to create deadly biological weapons. <a href="https://theconversation.com/could-gene-editing-tools-such-as-crispr-be-used-as-a-biological-weapon-82187">It’s an overlap</a> that’s helped <a href="https://thebulletin.org/2021/05/the-origin-of-covid-did-people-or-nature-open-pandoras-box-at-wuhan">fuel speculation</a> that the SARS-CoV-2 coronavirus was bioengineered at China’s Wuhan Institute of Virology and that it subsequently “escaped” through a lab accident to produce the COVID-19 pandemic. </p>
<p>The world already has <a href="https://dx.doi.org/10.1089%2Fhs.2017.0082">a legal foundation</a> to prevent gene splicing for warfare: <a href="https://www.un.org/disarmament/biological-weapons/">the 1972 Biological Weapons Convention</a>. Unfortunately, nations have been unable to agree on how to strengthen the treaty. <a href="https://fas.org/blogs/secrecy/2012/07/soviet_bw/">Some countries</a> have also pursued bioweapons research <a href="https://pubmed.ncbi.nlm.nih.gov/9244334/">and stockpiling</a> in violation of it.</p>
<p>As a member of President Bill Clinton’s National Security Council from 1996 to 2001, I had <a href="https://www.brandeis.edu/facultyguide/person.html?emplid=45b03f10247276eeaf30fadbc8afc2261b06795d">a firsthand view</a> of the failure to strengthen the convention. From 2009 to 2013, as President Barack Obama’s White House coordinator for weapons of mass destruction, I led <a href="https://www.armscontrol.org/act/2011-05/pursuing-prague-agenda-interview-white-house-coordinator-gary-samore">a team that grappled with</a> the challenges of regulating potentially dangerous biological research in the absence of strong international rules and regulations. </p>
<p>The history of the Biological Weapons Convention <a href="https://www.brookings.edu/blog/order-from-chaos/2017/09/06/the-biological-weapons-convention-at-a-crossroad/">reveals the limits</a> of international attempts to control research and development of biological agents. </p>
<h2>1960s-1970s: International negotiations to outlaw biowarfare</h2>
<p>The United Kingdom <a href="https://doi.org/10.1177/0096340211407400">first proposed</a> a <a href="https://ebookcentral.proquest.com/lib/brandeis-ebooks/detail.action?docID=3300058">global biological weapons ban</a> in 1968. </p>
<p>Reasoning that bioweapons had no useful military or strategic purpose given the awesome power of nuclear weapons, the U.K. had <a href="http://discovery.nationalarchives.gov.uk/details/r/C14396">ended its offensive bioweapons program</a> in 1956. But the risk remained that other countries might consider developing bioweapons as a <a href="https://doi.org/10.1177/0022002713509049">poor man’s atomic bomb</a>. </p>
<p>In the original British proposal, countries would have to identify facilities and activities with potential bioweapons applications. They would also need to accept on-site inspections by an international agency to verify these facilities were being used for peaceful purposes.</p>
<p>These negotiations gained steam in 1969 when <a href="https://www.jstor.org/stable/3092154">the Nixon administration ended</a> America’s offensive biological weapons program and supported the British proposal. <a href="https://legal.un.org/avl/ha/cpdpsbbtwd/cpdpsbbtwd.html">In 1971, the Soviet Union announced its support</a> – but only with the verification provisions stripped out. Since it was essential to get the USSR on board, the U.S. and U.K. agreed to drop those requirements. </p>
<p>In 1972 the treaty was finalized. After gaining the required signatures, it took effect in 1975. </p>
<p>Under <a href="https://treaties.unoda.org/t/bwc">the convention</a>, <a href="https://www.un.org/disarmament/biological-weapons/about/membership-and-regional-groups">183 nations have</a> agreed not to “develop, produce, stockpile or otherwise acquire or retain” biological materials that could be used as weapons. They also agreed not to stockpile or develop any “means of delivery” for using them. The treaty allows “prophylactic, protective or other peaceful” research and development – including medical research. </p>
<p>However, the treaty lacks any mechanism to verify that countries are complying with these obligations.</p>
<h2>1990s: Revelations of treaty violations</h2>
<p>This absence of verification was exposed as <a href="https://thebulletin.org/2019/11/the-biological-weapons-convention-protocol-should-be-revisited/">the convention’s fundamental flaw</a> two decades later, when it turned out that the Soviets had a great deal to hide. </p>
<p>In 1992, Russian President Boris Yeltsin revealed the Soviet Union’s massive <a href="https://fas.org/blogs/secrecy/2012/07/soviet_bw/">biological weapons program</a>. Some of <a href="https://doi.org/10.4159/9780674045132-007">the program’s reported experiments</a> involved making viruses and bacteria more lethal and resistant to treatment. <a href="https://doi.org/10.4159/harvard.9780674065260">The Soviets also</a> weaponized and mass-produced a number of dangerous naturally occurring viruses, including the anthrax and smallpox viruses, as well as the plague-causing <em>Yersinia pestis</em> bacterium. </p>
<p>Yeltsin in 1992 <a href="https://www.latimes.com/archives/la-xpm-1992-09-15-mn-859-story.html">ordered the program’s end</a> and the destruction of all its materials. <a href="https://www.atlanticcouncil.org/blogs/new-atlanticist/is-russia-violating-the-biological-weapons-convention/">But doubts remain</a> whether this was fully carried out. </p>
<p><a href="https://www.pbs.org/wgbh/nova/sciencenow/0401/02-hist-08.html">Another treaty violation</a> came to light after the U.S. defeat of Iraq in the 1991 Gulf War. United Nations inspectors discovered <a href="https://pubmed.ncbi.nlm.nih.gov/9244334/">an Iraqi bioweapons stockpile</a>, including 1,560 gallons (6,000 liters) of anthrax spores and 3,120 gallons (12,000 liters) of botulinum toxin. Both had been loaded into aerial bombs, rockets and missile warheads, although Iraq never used these weapons.</p>
<p>In the mid-1990s, during South Africa’s transition to majority rule, evidence emerged of <a href="https://unidir.org/publication/project-coast-apartheids-chemical-and-biological-warfare-programme">the former apartheid regime’s chemical and biological weapons program</a>. As revealed by the South African Truth and Reconciliation Commission, <a href="https://www.pbs.org/wgbh/pages/frontline/shows/plague/sa/">the program</a> focused on assassination. Techniques included infecting cigarettes and chocolates with anthrax spores, sugar with salmonella and chocolates with botulinum toxin. </p>
<p>In response to these revelations, <a href="https://doi.org/10.1017%2FS0002930000030098">as well as suspicions</a> that North Korea, Iran, Libya and Syria were also violating the treaty, the U.S. began urging other nations to close the verification gap. But despite 24 meetings over seven years, a specially formed group of international negotiators <a href="https://doi.org/10.1038/414675a">failed to reach agreement on how to do it</a>. The problems were both practical and political.</p>
<h2>Monitoring biological agents</h2>
<p>Several factors make verification of the bioweapons treaty difficult.</p>
<p>First, the types of facilities that research and produce biological agents, <a href="https://theconversation.com/3-medical-innovations-fueled-by-covid-19-that-will-outlast-the-pandemic-156464">such as vaccines</a>, antibiotics, vitamins, <a href="https://theconversation.com/can-random-bits-of-dna-lead-to-safe-new-antibiotics-and-herbicides-83550">biological pesticides</a> and <a href="https://theconversation.com/moving-beyond-pro-con-debates-over-genetically-engineered-crops-59564">certain foods</a>, can also produce biological weapons. Some pathogens with legitimate medical and industrial uses can also be used for bioweapons.</p>
<p>Further, large quantities of certain biological weapons can be produced quickly, by few personnel and in relatively small facilities. Hence, biological weapons programs are more difficult for international inspectors to detect than nuclear or chemical programs, which typically require large facilities, numerous personnel and years of operation.</p>
<p>So an effective bioweapons verification process would require nations to identify a large number of civilian facilities. Inspectors would need to monitor them regularly. The monitoring would need to be intrusive, allowing inspectors to demand “challenge inspections,” meaning access on short notice to both known and suspected facilities. </p>
<p>Finally, developing <a href="https://warontherocks.com/2020/05/the-pandemic-and-americas-response-to-future-bioweapons/">bioweapons defenses</a> – as permitted under the treaty – typically requires working with dangerous pathogens and toxins, and even delivery systems. So distinguishing <a href="https://www.lawfareblog.com/enhancing-biological-weapons-defense">legitimate biodefense programs</a> from illegal bioweapons activities often comes down to intent – and intent is hard to verify.</p>
<p>Because of these inherent difficulties, verification faced stiff opposition.</p>
<h2>Political opposition to bioweapons verification</h2>
<p>As the White House official responsible for coordinating the U.S. negotiating position, I often heard concerns and objections from important government agencies. </p>
<p>The Pentagon expressed fears that inspections of biodefense installations would compromise national security or lead to false accusations of treaty violations. The Commerce Department opposed intrusive international inspections on behalf of the pharmaceutical and biotechnology industries. Such inspections might compromise trade secrets, officials contended, or interfere with medical research or industrial production. </p>
<p>Germany and Japan, which also have large pharmaceutical and biotechnology industries, raised similar objections. China, Pakistan, Russia and others opposed nearly all on-site inspections. Since the rules under which the negotiation group operated required consensus, any single country could block agreement. </p>
<p>[<em>Like what you’ve read? Want more?</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=likethis">Sign up for The Conversation’s daily newsletter</a>.]</p>
<p>In January 1998, seeking to break the deadlock, <a href="https://fas.org/nuke/control/bwc/news/98022001_ppo.html">the Clinton administration proposed</a> reduced verification requirements. Nations could limit their declarations to facilities “especially suitable” for bioweapons uses, such as vaccine production facilities. Random or routine inspections of these facilities would instead be “voluntary” visits or limited challenge inspections – but only if approved by the executive council of a to-be-created international agency monitoring the bioweapons treaty. </p>
<p>But even this failed to achieve consensus among the international negotiators.</p>
<p>Finally, in July 2001, the George W. Bush administration <a href="http://www.sussex.ac.uk/Units/spru/hsp/documents/cbwcb53-Pearson.pdf">rejected the Clinton proposal</a> – ironically, on the grounds that it was not strong enough to detect cheating. With that, <a href="https://www.nytimes.com/2001/12/08/world/conference-on-biological-weapons-breaks-down-over-divisions.html">the negotiations collapsed</a>. </p>
<p>Since then, nations have made <a href="https://www.nytimes.com/2009/12/09/world/09biowar.html">no serious effort to establish a verification system</a> for the Biological Weapons Convention. </p>
<p>Even with the amazing advances scientists have made in genetic engineering since the 1970s, there are few signs that countries are interested in taking up the problem again. </p>
<p>This is especially true in today’s climate of accusations against China, and China’s refusal to fully cooperate to determine the origins of the COVID-19 pandemic.</p><img src="https://counter.theconversation.com/content/163472/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gary Samore 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 sketchy history of international efforts to control bioweapons suggests that nations will resist cooperative monitoring of gene hacking for medical research.Gary Samore, Professor of the Practice of Politics and Crown Family Director of the Crown Center for Middle East Studies, Brandeis UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1553492021-02-19T18:22:46Z2021-02-19T18:22:46ZThe human genome at 20: how biology’s most-hyped breakthrough led to anticlimax and arrests<figure><img src="https://images.theconversation.com/files/385281/original/file-20210219-21-rkb5rg.jpg?ixlib=rb-1.1.0&rect=40%2C0%2C8946%2C5982&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-illustration-virus-dna-molecule-structure-1371386951">Rost9/Shutterstock</a></span></figcaption></figure><p>When President Bill Clinton took to a White House lectern 20 years ago to announce that the <a href="https://home.bt.com/news/on-this-day/june-26-2000-the-book-of-life-falls-open-as-scientists-crack-the-human-genome-11363988716324">human genome sequence</a> had been completed, he hailed the breakthrough as “the most important, most wondrous map ever produced by humankind”. The scientific achievement was placed on par with the moon landings.</p>
<p>It was hoped that having access to the sequence would transform our understanding of human disease <a href="https://web.ornl.gov/sci/techresources/Human_Genome/project/clinton3.shtml">within 20 years</a>, leading to better treatment, detection and prevention. The famous <a href="https://science.sciencemag.org/content/291/5507/1304.full">journal article</a> that shared our genetic ingredients with the world, published in February 2001, was welcomed as a “Book of Life” that could revolutionise medicine by showing which of our genes led to which illnesses.</p>
<p>But in the two decades since, the sequence has underwhelmed. The potential of our newfound genetic self-knowledge has not been fulfilled. Instead, what has emerged is a new frontier in genetic research: new questions for a new batch of researchers to answer. </p>
<p>Today, the gaps between our genes, and the switches that direct genetic activity, are emerging as powerful determinants behind how we look and how we get ill – perhaps deciding <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877666/">up to 90%</a> of what makes us different from one another. Understanding this “<a href="https://theconversation.com/discovering-how-genetic-dark-matter-plays-a-role-in-mental-illness-is-just-the-tip-of-the-iceberg-for-human-health-142326">genetic dark matter</a>”, using the knowledge provided by the human genome sequence, will help us to push further into our species’ genetic secrets.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/C22JlzHlLJQ?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The announcement was first made in a joint press conference between President Bill Clinton and Prime Minister Tony Blair in 2000.</span></figcaption>
</figure>
<h2>Unravelled code</h2>
<p>Cracking the human genetic code took 13 years, US$2.7 billion (£1.9 billion) and hundreds of scientists peering through over 3 billion base pairs in our DNA. Once mapped, our genetic data helped projects like the <a href="https://depmap.sanger.ac.uk/">Cancer Dependency Map</a> and the <a href="https://www.genome.gov/about-genomics/fact-sheets/Genome-Wide-Association-Studies-Fact-Sheet">Genome Wide Association Studies</a> better understand the diseases that afflict humans.</p>
<p>But some results were disappointing. Back in 2000, as it was becoming clear the genome sequence was imminent, the genomics community began excitedly placing bets predicting how many genes the human genome would contain. Some bets were as high as 300,000, others as low as 40,000. For context, the onion genome contains 60,000 genes.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/explainer-what-is-a-gene-12951">Explainer: what is a gene?</a>
</strong>
</em>
</p>
<hr>
<p>Dispiritingly, it turned out that our genome contains roughly the same number of genes as a mouse or a fruit fly (around 21,000), and three times less than <a href="https://www.sciencedirect.com/science/article/abs/pii/S2352407316300166">an onion</a>. Few would argue that humans are three times less complex than an onion. Instead, this discovery suggested that the number of genes in our genome had little to do with our complexity or our difference from other species, as had been previously assumed.</p>
<h2>Great responsibility</h2>
<p>Access to the human genome sequence also presented the scientific community with a huge number of important <a href="https://pubmed.ncbi.nlm.nih.gov/1825074/">ethical questions</a>,
underscored in 2000 by Prime Minister Tony Blair when he cautioned: “With the power of this discovery comes the responsibility to use it wisely.”</p>
<p>Ethicists were particularly concerned about questions of “genetic discrimination”, like whether our genes could be used against us as evidence in a court of law, or as a basis for exclusion: a new kind of twisted hierarchy determined by our biology.</p>
<p>Some of these concerns were addressed by legislation against <a href="https://www.genome.gov/about-genomics/policy-issues/Genetic-Discrimination">genetic discrimination</a>, like the US Genetic Information Nondiscrimination Act of 2008. Other concerns, like those around so-called “designer babies”, are still being put to the test today.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/should-we-edit-the-genomes-of-human-embryos-a-geneticist-and-social-scientist-discuss-100355">Should we edit the genomes of human embryos? A geneticist and social scientist discuss</a>
</strong>
</em>
</p>
<hr>
<p>In 2018, human embryos were gene edited by a Chinese scientist, using a method called CRISPR which allows targeted sections of DNA to be snipped off and replaced with others. The scientist involved was subsequently <a href="https://www.nature.com/articles/d41586-020-00001-y">jailed</a>, suggesting that there remains little appetite for <a href="https://www.who.int/ethics/topics/human-genome-editing/WHO-Commissioned-Ethics-paper-March19.pdf">human genetic experimentation</a>. </p>
<p>On the other hand, to <a href="https://www.nature.com/articles/d41586-019-01906-z">deny available genetic treatments</a> to willing patients may one day be considered unethical – just as some countries have chosen to legalise euthanasia on ethical grounds. Questions remain about how humanity should handle its genetic data.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/th0vnOmFltc?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The Chinese scientist He Jiankui announced in 2018 that he had created gene-edited twins. He was jailed in 2019.</span></figcaption>
</figure>
<h2>Disease diversions</h2>
<p>With human gene editing still highly contentious, researchers have instead looked to find out which genes may be responsible for humanity’s illnesses. Yet when scientists <a href="https://www.genome.gov/about-genomics/fact-sheets/Genome-Wide-Association-Studies-Fact-Sheet">investigated which genes</a> are linked to human diseases, they were met with a surprise. After comparing huge samples of human DNA to find whether certain genes led to certain illnesses, they found that many unexpected sections of the genome were involved in the development of human disease.</p>
<p>The genome contains two sections: the coding genome, and the non-coding genome. The coding genome represents just 1.7% of our DNA, but is responsible for coding the proteins that are the essential building blocks of life. Genes are defined by their ability to code proteins: so 1.7% of our genome consists of genes. </p>
<p>The non-coding genome, which makes up the remaining 98.3% of our DNA, doesn’t code proteins. This largely unknown section of the genome was once dismissed as “junk DNA”, previously thought to be useless. It contained no protein-creating genes, so it was assumed the non-coding genome had little to do with the stuff of life.</p>
<p>Bewilderingly, scientists found that the <a href="https://science.sciencemag.org/content/306/5696/636.abstract">non-coding genome</a> was actually responsible for the majority of information that <a href="https://pubmed.ncbi.nlm.nih.gov/28622505/">impacted disease development</a> in humans. Such findings have made it clear that the non-coding genome is actually far more important than previously thought.</p>
<h2>Enhanced capabilities</h2>
<p>Within this non-coding part of the genome, researchers have subsequently found short regions of DNA called enhancers: gene switches that turn genes on and off in different tissues at different times. They found that enhancers needed to shape the embryo have changed very <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561167/">little during evolution</a>, suggesting that they represent a major and important source of genetic information.</p>
<p>These studies inspired one of us, Alasdair, to explore the possible role of enhancers in behaviours such as alcohol intake, anxiety and fat intake. By comparing the genomes of mice, birds and humans we identified an enhancer that has changed relatively little over 350 million years – suggesting its importance in species’ survival. </p>
<p>When we used CRISPR genome editing to delete this enhancer from the mouse genome, those mice <a href="https://pubmed.ncbi.nlm.nih.gov/31445429/">ate less fat</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/32203157/">drank less alcohol</a>, and displayed reduced anxiety. While these may all sound like positive changes, it’s likely that these enhancers evolved in calorifically poor environments full of predators and threats. At the time, eating high-calorie food sources such as fat and fermented fruit, and being hyper-vigilant of predators, would have been key for survival. However, in modern society these same behaviours may now contribute to obesity, alcohol abuse and chronic anxiety.</p>
<p>Intriguingly, subsequent genetic analysis of a <a href="https://www.ukbiobank.ac.uk/">major human population cohort</a> has shown that changes in the same human enhancer were also associated with <a href="https://pubmed.ncbi.nlm.nih.gov/32203157/">differences in alcohol intake and mood</a>. These studies demonstrate that enhancers are not only important for normal physiology and health, but that changing them could result in changes in behaviour that have major implications for human health.</p>
<p>Given these new avenues of research, we appear to be at a crossroads in genetic biology. The importance of gene enhancers in health and disease sits uncomfortably with our relative inability to identify and understand them. </p>
<p>And so in order to make the most of the sequencing of the human genome two decades ago, it’s clear that research must now look beyond the 1.7% of the genome that encodes proteins. In exploring uncharted genetic territory, like that represented by enhancers, biology may well locate the next swathe of healthcare breakthroughs.</p>
<p><em>This article was updated on February 21, 2021 to clarify that DNA base pairs are not made from proteins.</em></p><img src="https://counter.theconversation.com/content/155349/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Alasdair Mackenzie receives funding from the BBSRC, Tenovus (Scotland) and Medical Research Scotland</span></em></p><p class="fine-print"><em><span>Andreas Kolb does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The achievement didn’t live up to the hype, but it has illuminated new areas of ‘genetic dark matter’.Alasdair Mackenzie, Reader, Molecular Genetics, University of AberdeenAndreas Kolb, Senior Research Fellow, The Rowett Institute, University of AberdeenLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1536412021-02-01T18:58:20Z2021-02-01T18:58:20ZNew CRISPR technology could revolutionise gene therapy, offering new hope to people with genetic diseases<figure><img src="https://images.theconversation.com/files/381591/original/file-20210201-13-qr3zh4.jpg?ixlib=rb-1.1.0&rect=47%2C4%2C3147%2C1571&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>The day a muddled mob stormed the US Capitol building, a team of American researchers published a paper <a href="https://www.nature.com/articles/s41586-020-03086-7">in Nature</a> that signified a landmark in gene therapy.</p>
<p>The head of the US National Institutes of Health, Francis Collins had joined forces with Harvard University professor David Liu and others to tackle progeria, a genetic disorder that causes children to age rapidly. </p>
<p>The achievement, successfully tested in mice, was made possible by Liu’s invention of a second-generation CRISPR gene-editing technology called “base editing”. With this, researchers may eventually be able to correct lifelong genetic diseases, including <a href="https://www.webmd.com/children/progeria#1">progeria</a>, in humans.</p>
<h2>A rare but devastating disease</h2>
<p>Francis Collins, former leader of the Human Genome Project, had worked on progeria for many years before the breakthrough. </p>
<p>Children carrying the mutation for progeria have normal intelligence but show early signs of general ageing, including hair loss and hearing loss. By their teenage years they appear very old. Few live past the age of 13. </p>
<p>In 2003, Collins’s lab <a href="https://directorsblog.nih.gov/tag/progeria/">discovered</a> progeria is caused by a mutation (which you can think of as a “misspelling”) in a gene that encodes a protein called Lamin A. Lamin A has a structural role in the cell’s nucleus. </p>
<p>Many of us carry mutations in various genes. But as we typically have two copies of genes (one from our mother and one from our father), we tend to have at least one good copy and that’s usually enough.</p>
<p>But the progeria mutation in Lamin A is different. While there may be a good copy present, the mutant copy generates a poisonous product that messes things up, like a spanner in the works. This type of mutation is called a “dominant negative mutation”.</p>
<p>The solution, ideally, would be to specifically correct the mutant copy using <a href="https://theconversation.com/what-is-crispr-gene-editing-and-how-does-it-work-84591">CRISPR</a>. With this gene-editing tool, scientists can direct a pair of molecular “scissors” to any part of the genome (DNA). Unfortunately, first-generation CRISPR technologies — while good at cutting genes — do not have the level of surgical precision or efficiency needed to correct the Lamin A mutation. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/explainer-what-is-a-gene-12951">Explainer: what is a gene?</a>
</strong>
</em>
</p>
<hr>
<h2>Complications with mass cell editing</h2>
<p>CRISPR scissors are good at finding their target and cutting, but the reconstructive surgery that comes after is left to the cell — and isn’t guaranteed to happen in every cell. </p>
<p>In the lab, researchers can usually manage by just correcting a few cells before growing them in a petri dish for further research. </p>
<p>But in humans we need to accurately correct most, if not all, cells. It would be pointless to correct the progeria mutation in five cells in a patient’s finger, while leaving the rest of the body unrepaired.</p>
<p>This is where David Liu’s work on “base editors” is critical. Liu identified the limitations of CRISPR technology very early and began developing molecular machines that could do more than operate only as targeted molecular scissors. </p>
<p>He started with naturally occurring enzymes, which can change one type of chemical base of the genetic code into another; for example, enzymes that can convert an A (adenine) to a G (guanine), or a C (cytosine) to a T (thymine).</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/381581/original/file-20210201-23-o5yyqz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram showing basic DNA structure and chemical bases." src="https://images.theconversation.com/files/381581/original/file-20210201-23-o5yyqz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/381581/original/file-20210201-23-o5yyqz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/381581/original/file-20210201-23-o5yyqz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/381581/original/file-20210201-23-o5yyqz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/381581/original/file-20210201-23-o5yyqz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/381581/original/file-20210201-23-o5yyqz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/381581/original/file-20210201-23-o5yyqz.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">The double helix shape of DNA is supported by an alternating sugar-phsophate backbone (the sides). Attached to each sugar on the backbone is one of four chemical bases: adenine (A), thymine (T), guanine (G) and cytosine (C). The order of these bases is what determines an organism’s genetic code.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<p>Liu then modified the enzymes to make them more precise and fused them to CRISPR to create fusion proteins called “base editors”. Since CRISPR technology is good at reading DNA and finding a target, it can effectively deliver the editors to the gene that needs to be changed.</p>
<p>It’s important to highlight Liu deliberately developed base editors so that they change letters, but no longer sever DNA like CRISPR scissors. This is crucial, as cutting DNA increases the risk of larger chromosomal deletions, which can potentially damage cells.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/the-resilience-project-finding-those-rare-people-with-genetic-disease-mutations-who-are-healthy-57800">The Resilience Project: finding those rare people with genetic disease mutations who are healthy</a>
</strong>
</em>
</p>
<hr>
<h2>The differences of mice and men</h2>
<p>Collins, Liu and their colleagues knew they would have to get base editors into all (or at least <em>most</em>) of the cells of a mouse with progeria to cure it. For this, they relied on using hollowed-out viruses as delivery vectors. </p>
<p>They used a vector based on the Adeno Associated Virus, or AAV. As students, we joked AAV stood for “almost a virus”, as it’s one of the smallest viruses and doesn’t cause any known disease. </p>
<p>Collins and Liu packaged the AAV virus particles with genes encoding the relevant base-editing enzyme and delivered them into the mice. The treated mice essentially avoided the disease and became indistinguishable from healthy mice.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/GO306dK8m8c?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">In this video, Collins and Lui discuss their work involving treating progeria in mice.</span></figcaption>
</figure>
<p>But, of course, this all happened in mice — and humans are bigger. We don’t know how difficult it will be to upscale this gene-editing machinery to work reliably in humans. But in any case, Collins and Liu have taken an inspiring first step by showing it’s possible in mice. </p>
<p>Base-editing CRISPR tools are a dream come true for experts committed to gene therapy and for families afflicted by conditions such as progeria. Work on this front is just beginning. But in these dark pandemic times, it provides much-needed new hope.</p><img src="https://counter.theconversation.com/content/153641/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Merlin Crossley works for UNSW as Deputy Vice-Chancellor Academic and Student Experience, and a Professor of Molecular Biology. He holds or has held Australian Research Council and National Health and Medical Research Council grants, and collaborates with biotechnology companies, such as CSL and various international labs doing CRISPR-gene editing. He is on the Board of The Conversation, and Chair of the Editorial Board, Chair of UNSW Press, Deputy Director of the Australian Science Media Centre, and is an Honorary Associate of the Australian Museum. </span></em></p>Using ‘base editing’, researchers have cured progeria in mice. This genetic syndrome causes premature ageing in humans – those with the disease usually don’t live past the age of 13.Merlin Crossley, Deputy Vice-Chancellor Academic and Professor of Molecular Biology, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1536632021-01-22T18:20:40Z2021-01-22T18:20:40ZGene-edited crops are now a reality – but will the public be on board?<figure><img src="https://images.theconversation.com/files/379978/original/file-20210121-17-8zwcf3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Juice Flair / shutterstock</span></span></figcaption></figure><p>Once the UK left the EU, it would be free to <a href="https://www.fwi.co.uk/news/eu-referendum/boris-johnsons-vows-to-liberate-uk-from-eus-biotech-crops-stance">invest in gene editing of crops and livestock</a> to “feed the world”. That’s what the prime minister, Boris Johnson, told the House of Commons in 2019. And following the UK’s formal departure from the EU in January 2021, the government quickly launched a <a href="https://www.theguardian.com/science/2021/jan/07/gene-editing-of-crops-and-livestock-may-soon-be-permitted-in-england">public consultation</a> on the issue. </p>
<p>Yet media reporting might cause plant scientists to have unpleasant flashbacks to the 1990s, when genetically modified (or GM) crops were first being commercialised in Europe. Some of the language used to report on the consultation is eerily similar: the Daily Mail asks its readers whether “<a href="https://www.dailymail.co.uk/sciencetech/article-9119231/Government-consults-public-future-gene-editing-improve-crops-livestock.html">Frankenstein food</a>” is about to hit UK plates. Two decades ago, GM crops were also labelled “<a href="https://www.theguardian.com/environment/2021/jan/07/environment-department-scientist-calls-for-biotechnology-debate">Frankenfood</a>”.</p>
<p>Whereas GM crops typically contain the DNA of two different species, gene editing is more precise and allows scientists to tweak the DNA of a single species by itself. Today, many plant scientists see a clear difference between first-generation genetic modifications and the “<a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0229952">new plant breeding techniques</a>” of gene editing. These include tools like CRISPR, which can be used like “<a href="https://www.scientificamerican.com/article/nobel-prize-in-chemistry-goes-to-discovery-of-genetic-scissors-called-crispr-cas911/">genetic scissors</a>” to make changes to a plant that mimic natural variation.</p>
<p>In the US and Canada, for example, a non-browning mushroom has found a quick path to market thanks to breeders’ ability to “knock-out” the gene that <a href="http://www.nature.com/doifinder/10.1038/nature.2016.19754">controls the browning enzyme</a>, improving shelf-life and potentially minimising food waste. </p>
<p>Although this was done in a laboratory, natural processes at the genetic level – and in response to environmental conditions – turn genes “on and off” in a similar fashion. These tools have health applications, too. CRISPR is being used to <a href="https://doi.org/10.1038/s41392-020-00283-8">treat cancer</a> and has the potential for many more medical applications. </p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"993880292128690176"}"></div></p>
<p>Because gene-edited plants can be indistinguishable from their conventional cousins – unlike GM crops – countries around the world are <a href="https://journals.plos.org/plosbiology/article/comments?id=10.1371/journal.pbio.1002453">grappling</a> with <a href="http://www.nature.com/articles/d41586-019-02162-x">how they should be regulated</a>. In the European Union, a landmark 2018 ruling by the Court of Justice said that new gene-edited crops should be <a href="http://www.nature.com/articles/d41586-018-07166-7">governed by existing legislation</a> that was developed in response to first-generation GM crops and said that if you breed something that could not occur in nature, it counts as genetically-modified.</p>
<p>However, this does not mean – as was <a href="https://www.bbc.co.uk/news/science-environment-44953100">widely reported</a> – that gene-edited crops are automatically GM crops, which <a href="https://papers.ssrn.com/abstract=3730116">by definition</a> could not occur in nature. The EU, like the UK, is now revisiting this issue through a <a href="https://ec.europa.eu/food/plant/gmo/modern_biotech/new-genomic-techniques_en">consultation</a>.</p>
<h2>Involving the public</h2>
<p>As recipients of European plant science funding, we have seen that scientists and the public often talk past one another on the issue of biotechnology. Scientists, for their part, tend to view it in terms of risk (or lack thereof) and invoke humanity’s long history of <a href="https://theconversation.com/all-our-food-is-genetically-modified-in-some-way-where-do-you-draw-the-line-56256">modifying plants for our own purposes</a>. But we need to move beyond this framework and instead take account of the questions and concerns that the general public has about who benefits from this technology, who owns it and what impacts it will have.</p>
<p>First-generation genetic modification tended to focus on farm productivity. Protecting crops from pests was the top priority. Gene-edited crops could contribute to a wider variety of sustainability and health goals in future though, such as by improving nutrition or using resources more efficiently. In fact, a whole raft of technologies could be about to <a href="http://dx.doi.org/10.1038/s43016-020-0074-1">revolutionise the way we make food</a>. </p>
<p>However, as we learned with GM crops, technologies are most effective when the wider public and key stakeholders, such as farmers, are actively included in their development.</p>
<p>There is <a href="http://www.tandfonline.com/doi/abs/10.1080/23299460.2014.922249">greater</a> and <a href="https://www.sciencedirect.com/science/article/pii/S0048733313000930">greater</a> recognition among researchers and policymakers of the need to ensure that new technology meets the needs, expectations and values of the public. We have seen that <a href="https://link.springer.com/article/10.1007/s11136-014-0909-z">the involvement of patients</a> can make new health technologies more relevant and effective. Already, there is more talk of “<a href="http://online.ucpress.edu/elementa/article-pdf/doi/10.1525/elementa.405/434593/405-6995-1-pb.pdf">democratising</a>” new genomic tools like CRISPR. </p>
<p>So although plant scientists will hope to avoid repeating the same debates about biotechnology that they had two decades ago, there is still opportunity to gain public trust in these technologies through active and open dialogue. We must ask ourselves whether the gene editing consultation goes far enough to gain that trust, particularly for those that see this as Frankenstein-like technology.</p><img src="https://counter.theconversation.com/content/153663/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jonathan Menary receives funding from the European Union's Horizon 2020 research and innovation programme under grant agreements No 817690 and No 862127. This article reflects only the author's views. The European Commission is not responsible for any use that may be made of the information it contains.</span></em></p><p class="fine-print"><em><span>Sebastian Fuller receives funding from the European Union's Horizon 2020 research and innovation programme under grant agreements No 774078 and No 862127. This article reflects only the author's views. The European Commission is not responsible for any use that may be made of the information it contains.</span></em></p>Plant scientists hope to avoid a repeat of the GM foods debate from two decades ago.Jonathan Menary, Senior Research Associate, Lancaster Environment Centre, Lancaster UniversitySebastian Fuller, Postdoctoral Research Fellow, St George's, University of LondonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1476952020-10-08T02:54:47Z2020-10-08T02:54:47ZWhat is CRISPR, the gene editing technology that won the Chemistry Nobel prize?<p>The Royal Swedish Academy of Sciences yesterday <a href="https://www.nytimes.com/2020/10/07/science/nobel-prize-chemistry-crispr.html">awarded</a> the 2020 Nobel Prize in Chemistry to Emmanuelle Charpentier and Jennifer Doudna for <a href="https://science.sciencemag.org/content/337/6096/816.full">their work</a> on CRISPR, a method of genome editing.</p>
<p>A genome is the full set of genetic “instructions” that determine how an organism will develop. Using CRISPR, researchers can cut up DNA in an organism’s genome and edit its sequence.</p>
<p>CRISPR technology is a powerhouse for basic research and is also changing the world we live in. There are thousands of research papers published every year on its various applications.</p>
<p>These include accelerating research into <a href="https://www.cancer.gov/news-events/cancer-currents-blog/2020/crispr-cancer-research-treatment">cancers</a>, <a href="https://theconversation.com/discovering-how-genetic-dark-matter-plays-a-role-in-mental-illness-is-just-the-tip-of-the-iceberg-for-human-health-142326">mental illness</a>, potential animal to human <a href="https://www.technologyreview.com/2019/06/12/239014/crispr-pig-organs-are-being-implanted-in-monkeys-to-see-if-theyre-safe-for-humans/">organ transplants</a>, better <a href="https://www.nature.com/articles/s41477-018-0259-x">food production</a>, <a href="https://www.nature.com/articles/nbt.4245">eliminating malaria-carrying mosquitoes</a> and saving animals from <a href="https://www.nature.com/articles/d41586-018-06142-5">disease</a>. </p>
<p>Charpentier is the director at the Max Planck Institute for Infection Biology in Berlin, Germany and Doudna is a professor at the University of California, Berkeley. Both played a crucial role in demonstrating how CRISPR could be used to target DNA sequences of interest.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/why-more-women-dont-win-science-nobels-104370">Why more women don't win science Nobels</a>
</strong>
</em>
</p>
<hr>
<h2>Taking advantage of bacterial immunity</h2>
<p>CRISPR technology is adapted from a system that is naturally present in bacteria and other unicellular organisms known as <a href="https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/archaea">archaea</a>. </p>
<p>This natural system gives bacteria a form of acquired immunity. It protects them from foreign genetic elements (such as invading viruses) and lets them “remember” these in case they reappear.</p>
<p>Like most advances in modern science, the discovery of CRISPR and its emergence as a key genome editing method involved efforts by many researchers, over several decades.</p>
<p>In 1987, Japanese molecular biologist <a href="https://scholar.google.com/citations?user=Ku19X5UAAAAJ&hl=en">Yoshizumi Ishino</a> and his colleagues were <a href="https://doi.org/10.1128%2Fjb.169.12.5429-5433.1987">the first</a> to notice, in <a href="https://www.cdc.gov/ecoli/index.html">E. coli</a> bacteria, unusual clusters of repeated DNA sequences interrupted by short sequences.</p>
<p>Spanish molecular biologist Francisco Mojica and colleagues later showed similar structures were present in other organisms and proposed to call them CRISPR: Clustered Regularly Interspaced Short Palindromic Repeats.</p>
<p>In 2005, Mojica and other groups <a href="https://doi.org/10.1007%2Fs00239-004-0046-3">reported</a> the short sequences (or “spacers”) interrupting the repeats were derived from other DNA belonging to viruses.</p>
<p>Evolutionary biologists Kira Makarova, Eugene Koonin and colleagues eventually proposed CRISPR and the associated Cas9 genes were <a href="https://doi.org/10.1186%2F1745-6150-1-7">acting as the immune mechanism</a>. This was <a href="https://doi.org/10.1126%2Fscience.1138140">experimentally confirmed</a> in 2007 by Rodolphe Barrangou and colleagues.</p>
<p><iframe id="tc-infographic-229" class="tc-infographic" height="580px" src="https://cdn.theconversation.com/infographics/229/1e1ccd9abbd9a92604e144561050c08a9c49d8b3/site/index.html" width="100%" style="border: none" frameborder="0"></iframe></p>
<h2>A programmable system</h2>
<p>The CRISPR-associated genes, Cas9, encode a protein that “cuts” DNA. This is the active part of the defence against viruses, as it destroys the invading DNA.</p>
<p>In 2012, Charpentier and Doudna showed the <a href="https://www.livescience.com/58790-crispr-explained.html">spacers</a> acted as markers that guided where Cas9 would make a cut in the DNA. They also showed an artificial Cas9 system could be programmed to target any DNA sequence in a lab setting.</p>
<p>This was a groundbreaking discovery which opened the door for CRISPR’s wider applications in research.</p>
<p>In 2013, for the first time, groups led by American biochemist Feng Zhang and geneticist George Church reported genome editing in human cell cultures using CRISPR-Cas9. It has since been used in countless organisms from yeast to cows, plants and corals. </p>
<p>Today, CRISPR is the preferred gene-editing tool for thousands of researchers.</p>
<h2>A technical revolution with endless applications</h2>
<p>Humans have altered the genomes of species for thousands of years. Initially, this was through approaches such as selective breeding.</p>
<p>However, genetic engineering – the direct manipulation of DNA by humans outside of breeding and mutations – has only existed since the 1970s.</p>
<p>CRISPR-based systems fundamentally changed this field, as they allow for genomes to be edited in living organisms cheaply, with ease and with extreme precision.</p>
<p>CRISPR is currently making a huge <a href="https://biomedadvances.com/crispr-cas9-human-health/">impact in health</a>. There are clinical trials on its use for blood disorders such as sickle cell disease or beta-thalassemia, for the <a href="https://www.nature.com/articles/d41586-020-00655-8">treatment of</a> the most common cause of inherited childhood blindness (Leber congenital amaurosis) and for cancer immunotherapy.</p>
<p>CRISPR also has great potential in <a href="https://www.nationalgeographic.com/environment/future-of-food/food-technology-gene-editing/">food production</a>. It can be used to improve crop quality, yield, <a href="https://www.sciencedaily.com/releases/2018/05/180510101245.htm#">disease resistance</a> and herbicide resistance. </p>
<p>Used on livestock, it can lead to better disease resistance, increased animal welfare and improved productive traits – that is, animals producing more meat, milk or high-quality wool.</p>
<h2>With great power…</h2>
<p>A number of challenges to the technology remain, however. Some are technical, such as the risk of off-target modifications (which happen when Cas9 cuts at unintended locations in the genome).</p>
<p>Other problems are societal. CRISPR was famously used in one of the most controversial experiments of recent years. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/why-we-need-a-global-citizens-assembly-on-gene-editing-146398">Why we need a global citizens' assembly on gene editing</a>
</strong>
</em>
</p>
<hr>
<p>Chinese biophysicist He Jiankui unsuccessfully <a href="https://theconversation.com/chinas-failed-gene-edited-baby-experiment-proves-were-not-ready-for-human-embryo-modification-128454">attempted</a> to use the technology to modify human embryos and make them resistant to HIV (human immunodeficiency virus). This led to the birth of twins Lulu and Nana.</p>
<p>We need a broad and inclusive discussion on the regulation of such technologies – especially given their vast applications and potential.</p>
<p>To <a href="https://twitter.com/UrnovFyodor/status/1313800879670091776">quote CRISPR researcher Fyodor Urnov</a>, Charpentier and Doudna’s work really has “changed everything”.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1313800879670091776"}"></div></p><img src="https://counter.theconversation.com/content/147695/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Dimitri Perrin has received funding from the Australian Research Council (ARC), the Australian-French Association for Innovation and Research (AFRAN), and the Advance Queensland programme.</span></em></p>Jennifer Doudna and Emmanuelle Charpentier have been awarded the Nobel prize in Chemistry for their revolutionary work on ‘gene scissors’ that can edit DNA.Dimitri Perrin, Senior Lecturer, Queensland University of TechnologyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1477012020-10-07T23:40:27Z2020-10-07T23:40:27ZNobel Prize for chemistry honors exquisitely precise gene-editing technique, CRISPR – a gene engineer explains how it works<figure><img src="https://images.theconversation.com/files/362192/original/file-20201007-14-1nfwjm5.jpg?ixlib=rb-1.1.0&rect=34%2C28%2C3782%2C2536&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">American biochemist Jennifer A. Doudna, left, and French microbiologist Emmanuelle Charpentier were awarded this year's Nobel Prize for chemistry.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/march-2016-hessen-frankfurt-main-the-american-biochemist-news-photo/1228935175?adppopup=true">Alexander Heinl/picture alliance via Getty Images</a></span></figcaption></figure><p>Researchers have been able to manipulate large chunks of genetic code for almost 50 years. But it is only within the past decade that they have been able to do it with exquisite precision – adding, deleting and substituting single units of the genetic code just as an editor can manipulate a single letter in a document. This newfound ability is called gene editing, the tool is called CRISPR, and it’s being used worldwide to engineer plants and livestock and treat disease in people.</p>
<p>For these reasons the <a href="https://www.nobelprize.org/prizes/chemistry/2020/press-release/">2020 Nobel Prize in chemistry</a> has been awarded to <a href="https://scholar.google.fr/citations?user=fZJ8R-QAAAAJ&hl=fr">Emmanuelle Charpentier</a>, director of the Max Planck Unit for the Science of Pathogens in Germany, and <a href="https://scholar.google.com/citations?user=YO5XSXwAAAAJ&hl=en">Jennifer Doudna</a>, professor at the University of California, Berkeley, for discovering and transforming CRISPR into a gene-editing technology. It’s the first time two women have shared a Nobel prize. </p>
<p><a href="https://www.che.ufl.edu/jain/">I’m a CRISPR engineer</a>, interested in developing novel CRISPR-based gene-editing tools and delivery methods to improve their precision and function. </p>
<p>In the past, my colleagues and I have created a version of CRISPR that can be <a href="https://doi.org/10.1002/anie.201606123">controlled using light</a>, which allows precise control of where and when gene editing is performed in cells, and can be potentially used in animals and humans. We’ve also created <a href="https://doi.org/10.1039/C9NR01786K">a targeted system</a> that can package and deliver the editing components to desirable cell types – it’s like GPS for cells. Most recently, we engineered a tool <a href="https://doi.org/10.1038/s41467-020-18615-1">that improved the speed and precision of CRISPR</a> so it could be used in rapid diagnostic kits for <a href="https://theconversation.com/rapid-home-based-coronavirus-tests-are-coming-together-in-research-labs-were-working-on-analyzing-spit-using-advanced-crispr-gene-editing-techniques-138064">COVID-19, HIV, HCV and prostate cancer</a>. </p>
<p>While CRISPR scientists like me have been speculating about a Nobel Prize for CRISPR, it was exciting to see Charpentier and Doudna win. This will encourage young, talented engineers and researchers to enter the field of gene editing, which can be leveraged for designing new diagnostics, treatments and cures for a range of diseases. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/362274/original/file-20201007-22-xl6nvl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/362274/original/file-20201007-22-xl6nvl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=300&fit=crop&dpr=1 600w, https://images.theconversation.com/files/362274/original/file-20201007-22-xl6nvl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=300&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/362274/original/file-20201007-22-xl6nvl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=300&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/362274/original/file-20201007-22-xl6nvl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=377&fit=crop&dpr=1 754w, https://images.theconversation.com/files/362274/original/file-20201007-22-xl6nvl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=377&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/362274/original/file-20201007-22-xl6nvl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=377&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Gene-editing technology enables researchers to edit the DNA of organisms and reprogram them.</span>
<span class="attribution"><a class="source" href="https://www.nobelprize.org/uploads/2020/10/chemistry-2020-figure1-m-copy.pdf">Johan Jarnestad/The Royal Swedish Academy of Sciences</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<h2>CRISPR/Cas systems as gene editors</h2>
<p>Many variants of CRISPR/Cas systems have been discovered, engineered and applied to edit genes. There are already over <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22CRISPR%22">20,000 scientific publications</a> on the topic. </p>
<p>CRISPR dates back to 1987, when a Japanese molecular biologist, Yoshizumi Ishino, and colleagues discovered <a href="https://doi.org/10.1128/jb.169.12.5429-5433.1987">a CRISPR DNA sequence</a> in <em>E. coli</em>. The CRISPR sequence was later characterized by a Spanish scientist, Francisco Mojica, and colleagues, who named it CRISPR, which stands for <a href="https://doi.org/10.1046/j.1365-2958.2002.02839.x">Clustered Regularly Interspaced Short Palindromic Repeats</a>. </p>
<p>While people and animals have evolved complex immune systems to fight viral attacks, single-cell microorganisms rely on CRISPR to find and destroy a virus’s genetic material to stop it from multiplying. </p>
<p>Charpentier and Doudna figured out how to borrow this innate biological capability from microbes and apply it to genetic engineering of bacteria.</p>
<p>In a landmark paper, published online on June 28, 2012, Charpentier and Doudna showed that the CRISPR gene-editing machinery includes two components: a guide molecule that serves as sort of a GPS to find and bind the target gene site on the DNA of an invading virus, which then teams up with a CRISPR-associated protein (Cas) that serves as a molecular scissor <a href="https://doi.org/10.1126/science.1225829">that snips the DNA</a>. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/TdBAHexVYzc?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Jennifer Doudna explains what CRISPR is and how it is used.</span></figcaption>
</figure>
<p>Around the same time, <a href="https://www.researchgate.net/scientific-contributions/39194791-Virginijus-Siksnys">Virginijus Siksnys</a>, a Lithuanian biochemist at the University of Vilnius, made a similar discovery and submitted results for publication that appeared a few months later, in <a href="https://www.pnas.org/content/109/39/E2579">September 2012</a>. <a href="https://scholar.google.com/citations?user=B5QpZooAAAAJ&hl=en">Feng Zhang</a>, a biologist at the Broad Institute in Cambridge, Massachusetts, and colleagues showed that CRISPR can be improved and used for <a href="https://doi.org/10.1126/science.1231143">editing mammalian cells</a>. He currently owns one of the first patents on using CRISPR for gene editing, which is being <a href="https://www.sciencemag.org/news/2020/09/latest-round-crispr-patent-battle-has-apparent-victor-fight-continues">contested</a> by Doudna’s institution, UC Berkeley. </p>
<p>Once the DNA has been cut in the right spot, the cell will try to repair the cut. But the repair mechanism is error prone, and oftentimes the cells fail to fix the cuts perfectly, ultimately disabling the gene. Disrupting a gene is particularly useful for studying its function and find out what happens if you stop a gene from working. This technique is also useful for treating cancer and infections, where turning off a gene can potentially stop cancer cells and pathogens from dividing or kill them outright. </p>
<p>During this cutting-repair process, one can fool the cells by providing a new piece of DNA. The cells will then incorporate this piece of DNA with desirable edits into the genetic code. This enables researchers to correct a genetic mutation that causes a genetic disease, or replace a defective gene with a healthy one. </p>
<p>The beauty of CRISPR lies in its simplicity. CRISPR can be easily customized to target any gene of interest, whether it is in plants, animals or people. CRISPR applications range from tools for understanding biology, as diagnostics and <a href="https://doi.org/10.1038/s41571-019-0166-8">as new kinds of therapeutics</a> to <a href="http://doi.org/10.1016/j.cell.2014.05.010">applications in producing better crops, biofuels and transplantable organs</a>.</p>
<p>[<em>The Conversation’s science, health and technology editors pick their favorite stories.</em> <a href="https://theconversation.com/us/newsletters/science-editors-picks-71/?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=science-favorite">Weekly on Wednesdays</a>.]</p>
<h2>Why CRISPR deserved a Nobel Prize</h2>
<p>While there is still plenty of room for improvement of these technologies, scientists have already begun testing CRISPR in a number of <a href="https://clinicaltrials.gov/ct2/results?cond=&term=CRISPR&cntry=&state=&city=&dist=">clinical trials</a> for treating cancer and genetic disorders. CRISPR-based diagnostics have been also been approved by the U.S. Food and Drug Administration under emergency use authorization for <a href="https://www.nature.com/articles/d41586-020-01402-9">COVID-19 testing</a>. </p>
<p>CRISPR does come with a lot of ethical concerns that warrant caution. For example, in 2018, a Chinese scientist prematurely and unethically used CRISPR for editing human embryos and created <a href="https://theconversation.com/us/topics/crispr-edited-baby-63150">CRISPR-edited babies</a> that could pass these genetic alterations to their offspring for generations to come. Some have used the technology for <a href="https://www.popularmechanics.com/science/a19067/11-crazy-things-we-can-do-with-crispr-cas9/">other CRISPR-related DIY biohacks</a> that raise more <a href="https://www.vox.com/future-perfect/2019/8/13/20802059/california-crispr-biohacking-illegal-josiah-zayner">concerns over regulating the gene-editing technology</a>. </p>
<p>Despite these concerns, CRISPR has huge potential to transform how scientists can <a href="https://theconversation.com/rapid-home-based-coronavirus-tests-are-coming-together-in-research-labs-were-working-on-analyzing-spit-using-advanced-crispr-gene-editing-techniques-138064">detect</a>, <a href="https://theconversation.com/how-gene-edited-white-blood-cells-are-helping-fight-cancer-126806">treat</a> and even <a href="https://theconversation.com/using-gene-drives-to-control-wild-mosquito-populations-and-wipe-out-malaria-104613">eradicate diseases</a> as well as improve agricultural products. Society is already seeing the benefits of this Nobel-winning technology.</p><img src="https://counter.theconversation.com/content/147701/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Piyush K. Jain receives funding from the Florida Breast Cancer Foundation. </span></em></p>The tools to rewrite the genetic code to improve crops and livestock, or to treat genetic diseases, has revolutionized biology. A CRISPR engineer explains why this technology won the Nobel, and its potential.Piyush K. Jain, Assistant Professor of Chemical Engineering, Herbert Wertheim College of Engineering, UF Health Cancer Center, University of FloridaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1477302020-10-07T23:15:23Z2020-10-07T23:15:23ZNobel Prize for CRISPR honors two great scientists – and leaves out many others<figure><img src="https://images.theconversation.com/files/362282/original/file-20201007-14-pjrk6r.jpg?ixlib=rb-1.1.0&rect=54%2C998%2C5997%2C3747&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">CRISPR enables editing DNA with unprecedented precision.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/genome-editing-royalty-free-image/1153361167">wildpixel/iStock via Getty Images</a></span></figcaption></figure><p>The gene-editing technique <a href="https://www.nobelprize.org/prizes/chemistry/2020/summary/">CRISPR earned the 2020 Nobel Prize in chemistry</a>. Recognition of this amazing breakthrough technology is well deserved.</p>
<p>But each Nobel Prize can be awarded to <a href="https://theconversation.com/how-fair-is-it-for-just-three-people-to-receive-the-nobel-prize-in-physics-85161">no more than three people</a>, and that’s where this year’s prize gets really interesting. </p>
<p>The decision to award the prize to <a href="https://scholar.google.com/citations?user=YO5XSXwAAAAJ&hl=en&oi=ao">Jennifer Doudna</a> and <a href="https://www.emmanuelle-charpentier-lab.org">Emmanuelle Charpentier</a> involves geopolitics and patent law, and it pits basic science against applied science.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/362283/original/file-20201007-22-4ispcq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="award announcements with winners projected on a slide" src="https://images.theconversation.com/files/362283/original/file-20201007-22-4ispcq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/362283/original/file-20201007-22-4ispcq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=405&fit=crop&dpr=1 600w, https://images.theconversation.com/files/362283/original/file-20201007-22-4ispcq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=405&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/362283/original/file-20201007-22-4ispcq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=405&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/362283/original/file-20201007-22-4ispcq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=509&fit=crop&dpr=1 754w, https://images.theconversation.com/files/362283/original/file-20201007-22-4ispcq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=509&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/362283/original/file-20201007-22-4ispcq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=509&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">At the announcement of the winners of the 2020 Nobel Prize in chemistry, Emmanuelle Charpentier (onscreen left) and Jennifer Doudna (onscreen right).</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/professor-pernilla-wittung-stafshede-and-goran-k-hansson-news-photo/1228934991">Henrik Montgomery/TT News Agency/AFP via Getty Images</a></span>
</figcaption>
</figure>
<h2>Editing letters in the book of life</h2>
<p>CRISPR is a powerful gene-editing tool that has taken molecular biology from the typewriter to the word processor age. One could say it’s like Microsoft Word for the book of life. CRISPR allows a researcher to find not just a gene, but a very specific part of a gene and change it, delete it or add a completely foreign gene. Genetic modifications that used to take sophisticated biological laboratories years to do are now done in days and at <a href="https://www.addgene.org/guides/crispr/">significantly less cost</a>. </p>
<p>The CRISPR story begins in 1987, when molecular biologist <a href="https://hyoka.ofc.kyushu-u.ac.jp/search/details/K001659/english.html">Yoshizumi Ishino</a> and his co-workers discovered a strange palindromic stretch of DNA in <em>E. coli</em>, a commonly studied stomach bacteria. No one could imagine <a href="https://doi.org/10.1128/jb.169.12.5429-5433.1987">what purpose it served</a>.</p>
<p>By 2002, DNA sequencing methods were cheaper and more common, and researchers had found Ishino’s repeat sequences in nearly half of all bacteria and most of the single-celled archaea that had been sequenced. At this point there were enough puzzle pieces for <a href="https://scholar.google.com/citations?user=wtNG-xkAAAAJ&hl=en&oi=ao">Francisco Mojica</a> at the University of Alicante and <a href="https://www.researchgate.net/profile/Ruud_Jansen">Ruud Jansen</a> at Utrecht University to come up with a great acronym: CRISPR – for Clustered Regularly Interspaced Short Palindromic Repeats.</p>
<p>Nearly five years later, at the National Center for Biotechnology Information in Bethesda, Maryland, <a href="https://scholar.google.com/citations?user=F4P3ghEAAAAJ&hl=en&oi=ao">Eugene Koonin</a> established the odd DNA’s function as <a href="https://doi.org/10.1098/rstb.2018.0087">a bacterial defense system composed of two parts</a>. The first is a stretch of DNA that acts as an album of vanquished foes. When the bacterium overcomes an enemy, it snips out a section of the defeated invaders’ genetic material and places it into the album. These genetic mug shots are separated by repetitive stretches of DNA that read the same forward or backward. These palindromic bits of DNA are the PR in CRISPR.</p>
<p>The second component of the bacterial defense system is a search-and-destroy weapon. Each genetic mug shot has a search-and-destroy protein associated with it called a CRISPR-associated (Cas) protein. These Cas proteins circulate inside the cell, and when they encounter a stretch of genetic material corresponding to their genetic mug shot target, they kill the invader.</p>
<p>It took 20 years and much research to discover and understand these proteins.</p>
<p>Then in 2007, Danisco, a Danish food and beverage company, confirmed Koonin’s hypothesis that CRISPR is a bacterial defense system. Today, most yogurt and cheese manufacturers include CRISPR sequences in their cultures to protect their products from common viral outbreaks. <a href="https://www.quantamagazine.org/crispr-natural-history-in-bacteria-20150206/">According to Rodolphe Barrangou</a>, who conducted this research at Danisco USA: “If you’ve eaten yogurt or cheese, chances are you’ve eaten CRISPR-ized cells.”</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/362280/original/file-20201007-18-182n3ew.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="computer-generated illustration of CRISPR ribonucleoprotein" src="https://images.theconversation.com/files/362280/original/file-20201007-18-182n3ew.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/362280/original/file-20201007-18-182n3ew.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/362280/original/file-20201007-18-182n3ew.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/362280/original/file-20201007-18-182n3ew.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/362280/original/file-20201007-18-182n3ew.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/362280/original/file-20201007-18-182n3ew.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/362280/original/file-20201007-18-182n3ew.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A Cas protein gets to work snipping out an offending bit of DNA.</span>
<span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/AldevronNowOfferingaCRISPRRibonucleoproteinManufacturingServiceforClinicalApplications/177b8e66bc4ad85a9141f619776ccca5/photo?Query=CRISPR&mediaType=photo&sortBy=arrivaldatetime:desc&dateRange=Anytime&totalCount=10&currentItemNo=2">Business Wire/AP Photo</a></span>
</figcaption>
</figure>
<h2>Harnessing CRISPR’s potential</h2>
<p>Jennifer Doudna, a biochemist with extensive experience working with RNA at the University of California, Berkeley, started working with CRISPR in 2006. At a 2011 American Society for Microbiology meeting in San Juan, Puerto Rico, she met Emmanuelle Charpentier, an associate professor at the Laboratory for Molecular Infection Medicine Sweden at Umeå, who worked on a particular CRISPR-associated protein called Cas9.</p>
<p>Doudna and Charpentier had complementary skills. While walking around the old town of San Juan, Charpentier convinced Doudna that Cas9 was responsible for finding the DNA sequence that corresponds to the mug shot and cutting it. Doudna was intrigued and agreed to take a closer look at the <a href="https://www.hmhbooks.com/shop/books/A-Crack-in-Creation/9781328915368">role Cas9 played</a>.</p>
<p>Charpentier worked with Cas9 in <em>Streptococcus pyogenes</em>, the bacteria that cause strep throat and flesh-eating disease. Rather than send Doudna these dangerous bacteria, she overnighted her the DNA encoding the CRISPR-Cas9. The more Doudna studied Charpentier’s molecular scissors, the more obvious it became to her that this bacterial system could be co-opted to edit DNA. She was right, and with some tweaking, she converted CRISPR-Cas9 into a gene editing tool. Doudna noted in her memoir that CRISPR-Cas9 “<a href="https://www.hmhbooks.com/shop/books/A-Crack-in-Creation/9781328915368">was the perfect bacterial weapon</a>: a virus-seeking missile that could strike quickly and with incredible precision.”</p>
<p>Doudna and her collaborators wrote up their results and submitted their manuscript to the journal Science, which fast-tracked the paper and published it days after submission. Around the same time, she filed a patent application for the CRISPR-Cas9 gene-editing system.</p>
<p>Meanwhile, <a href="https://doi.org/10.1038/d41586-018-05308-5">Virginijus Siksnys</a>, a molecular biologist at Vilnius University in Lithuania with a research background in a class of proteins that cut DNA called restriction endonucleases, also foresaw the CRISPR system’s potential. He submitted his own results to the journal Cell. The editor rejected the manuscript without sending it out for review. Siksnys, confident in his work and its importance, submitted his manuscript to the <a href="https://doi.org/10.1073/pnas.1208507109">Proceedings of the National Academy of Sciences</a>. The paper was sent in before Doudna’s paper was published, but it needed some revisions and was thus published three months after Doudna’s paper appeared.</p>
<p>Like Doudna and Siksnys, <a href="https://scholar.google.com/citations?user=B5QpZooAAAAJ&hl=en&oi=ao">Feng Zhang</a>, a professor of neuroscience at MIT, was using the CRISPR-Cas9 system to edit DNA. But while the others did all their editing in solution, Zhang was slicing and dicing DNA with CRISPR-Cas9 in human cells. In January 2013, Zhang published his own <a href="https://doi.org/10.1126/science.1231143">Science paper</a>. At this time, even though Doudna had applied for a patent seven months earlier, Feng Zhang asked his employers, MIT and the Broad Institute, <a href="https://www.kqed.org/science/1938007/making-sense-of-the-crispr-patent-dispute-between-the-university-of-california-and-broad">to file a patent on his behalf</a>. </p>
<p>The Broad Institute lawyers, knowing that Doudna’s claim was pending, paid an additional fee to accelerate their patent application. It worked, and they were granted a CRISPR-Cas9 patent before Doudna was eventually awarded hers. This has started a closely watched legal battle. The contest is far from over, but it seems that Doudna is winning the <a href="https://www.labiotech.eu/crispr/crispr-patent-europe/">legal battle in the EU</a> and <a href="https://www.sciencemag.org/news/2020/09/latest-round-crispr-patent-battle-has-apparent-victor-fight-continues">Zhang in the U.S</a>. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/362284/original/file-20201007-14-3c8k4f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Doudna and Zhang seated on a stage" src="https://images.theconversation.com/files/362284/original/file-20201007-14-3c8k4f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/362284/original/file-20201007-14-3c8k4f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/362284/original/file-20201007-14-3c8k4f.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/362284/original/file-20201007-14-3c8k4f.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/362284/original/file-20201007-14-3c8k4f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/362284/original/file-20201007-14-3c8k4f.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/362284/original/file-20201007-14-3c8k4f.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">Jennifer Doudna (left) shares a stage with Feng Zhang (right) while a journalist leads a public discussion of CRISPR in 2015.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/professor-of-chemistry-and-of-molecular-and-cell-biology-at-news-photo/491145088">Anna Webber/Getty Images Entertainment via Getty Images</a></span>
</figcaption>
</figure>
<h2>Politics around the prize</h2>
<p>The decision to award the Nobel Prize to Doudna and Charpentier couldn’t have been easy. By choosing these two over Feng Zhang, the Royal Swedish Academy of Sciences sent a major message. It could have awarded the prize to a third researcher, but it didn’t. Was it a statement intended for the legal system?</p>
<p>Fortunately, scientists using CRISPR as a molecular editor aren’t affected by the legal battles. They can get their CRISPR systems from the <a href="https://www.addgene.org/crispr/#?">Addgene</a> open-source repository. Clinical applications of CRISPR – like finding a cure for genetic diseases such as cystic fibrosis and sickle cell anemia – will most likely be affected by the legal wranglings, as that is the technology’s <a href="https://doi.org/10.1089/blr.2020.29180.ac">most commercial use</a>.</p>
<p>Often, basic science research goes nowhere. Often it goes in unexpected directions. Sometimes it leads to the most excitingly splendid conclusions. CRISPR-Cas9 is one of these cases. It started with a weirdly repeating palindrome, matured via mozzarella and yogurt and finally blossomed into a contested gene-editing tool that was awarded the 2020 Nobel Prize.</p>
<p><em>This article has been updated to include Francisco Mojica and Ruud Jansen in the description of early CRISPR research.</em></p><img src="https://counter.theconversation.com/content/147730/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Marc Zimmer 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>Most scientific discoveries these days aren’t easily ascribed to a single researcher. CRISPR is no different – and ongoing patent fights underscore how messy research can be.Marc Zimmer, Professor of Chemistry, Connecticut CollegeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1463982020-09-17T19:50:14Z2020-09-17T19:50:14ZWhy we need a global citizens’ assembly on gene editing<figure><img src="https://images.theconversation.com/files/358550/original/file-20200917-24-1wko0xl.jpg?ixlib=rb-1.1.0&rect=206%2C188%2C5784%2C3799&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Developments in <a href="https://theconversation.com/au/topics/gene-editing-18986">gene editing</a> are often met with moral panic. Every new announcement raises outrage over the audacity of scientists “playing God”. The existence of <a href="https://theconversation.com/mutant-malaria-parasites-resistant-to-antimalarial-atovaquone-cannot-spread-new-research-57359">mutant mosquitoes</a> and <a href="https://edition.cnn.com/2019/08/16/opinions/gene-edit-dangers-opinion-klitzman/index.html">designer babies</a> are often framed as threats – evidence that science fiction has crossed over into real life.</p>
<p>There are clear dangers when the language of fear and scandal hijack public conversations on complex matters. But this doesn’t mean we should leave the discussion on genome editing – the process of altering an organism’s genetic sequence to produce favourable characteristics or remove unwanted ones – solely to scientists.</p>
<p>That danger was sharply underscored in 2018, when a young Chinese researcher announced he had engineered the birth of what may very well be the <a href="https://theconversation.com/designer-babies-wont-be-common-anytime-soon-despite-recent-crispr-twins-108342">first genetically modified humans</a>. “I feel proud,” he told the public, a year before he was <a href="https://www.sciencemag.org/news/2019/12/chinese-scientist-who-produced-genetically-altered-babies-sentenced-3-years-jail">jailed for forgery</a>.</p>
<p>And so we reach an impasse. As global leaders face pressure to regulate genome editing, questions about who drives these ethical debates persist. Should leaders listen to scientists, who may be vulnerable to moral blindness, or to the public, some of whom may be convinced their last Whopper contained a Frankenfood patty because an Instagram influencer told them so?</p>
<h2>The impasse doesn’t have to be permanent</h2>
<p>In recent years, ordinary citizens have become more empowered to collectively learn, deliberate, reflect, and put forward recommendations on divisive and technical policy issues. The <a href="https://www.oecd.org/gov/innovative-citizen-participation-and-new-democratic-institutions-339306da-en.htm">OECD</a> calls this the “<a href="https://carnegieeurope.eu/2019/11/26/new-wave-of-deliberative-democracy-pub-80422">deliberative wave</a>”. Processes like citizen juries or online town halls have been used to provide public input not only on topical issues such as <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/j.1369-7625.2010.00637.x">e-health</a> or <a href="https://www.tandfonline.com/doi/abs/10.1080/13549839708725520?journalCode=cloe20">waste management</a>, but also on issues that affect future generations, like <a href="https://connect2parliament.com/resources/">mitochondiral donation</a>.</p>
<p><a href="https://citizensassemblies.org/">Citizens’ assemblies</a> are forums in which a randomly selected, demographically diverse group of laypeople come together, typically for several days at a time, to deliberate over a policy issue. This allows them to learn more about the issue, scrutinise expert information, engage the arguments of advocates representing different sides, and deliberate with their fellow participants about possible ways forward.</p>
<p>These assemblies can be viewed as a counterbalance to the growing prevalence of public conversations shaped by disinformation, clickbait culture, hyper-partisanship, and distrust of experts.</p>
<p>A citizens’ assembly is a fitting approach to clarify controversies on genome editing, particularly around its ethics.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/358551/original/file-20200917-20-1r0pmxw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Embryo modification illustration" src="https://images.theconversation.com/files/358551/original/file-20200917-20-1r0pmxw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/358551/original/file-20200917-20-1r0pmxw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=348&fit=crop&dpr=1 600w, https://images.theconversation.com/files/358551/original/file-20200917-20-1r0pmxw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=348&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/358551/original/file-20200917-20-1r0pmxw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=348&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/358551/original/file-20200917-20-1r0pmxw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=437&fit=crop&dpr=1 754w, https://images.theconversation.com/files/358551/original/file-20200917-20-1r0pmxw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=437&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/358551/original/file-20200917-20-1r0pmxw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=437&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A citizens’ assembly on gene editing would allow for democratic deliberation on the risks involved.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<h2>A groundbreaking global experiment</h2>
<p>We are among 25 experts on deliberative democracy and genome editing who have <a href="https://science.sciencemag.org/cgi/doi/10.1126/science.abb5931">published an article today in the journal Science</a>, making a case for a <a href="https://www.globalca.org/">Global Citizens’ Assembly on Genome Editing</a> </p>
<p>We envisage a process that would convene at least 100 people from all over the world, none of whom can claim expertise or a history of advocacy on this issue. After learning about the issue from a national perspective, they would gather for five days to deliberate over whether there should be a set of global principles for the regulation of genome editing technologies. The challenge of getting a representative sample of the world is not lost on us, although we are committed to ensuring a broad spread of participants representing different nationalities, ages, religions, levels of education, genders and cultures. </p>
<p>This would be a groundbreaking global experiment. It would be the first example of a global citizens’ assembly, and it remains to be seen whether national governments and institutions such as the World Health Organisation and the Food and Agriculture Organisation would seriously consider its recommendations.</p>
<p>But there are good reasons to think our global citizens’ assembly would be a meaningful undertaking.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/358552/original/file-20200917-18-u5zhop.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Illustration of a round table" src="https://images.theconversation.com/files/358552/original/file-20200917-18-u5zhop.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/358552/original/file-20200917-18-u5zhop.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=574&fit=crop&dpr=1 600w, https://images.theconversation.com/files/358552/original/file-20200917-18-u5zhop.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=574&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/358552/original/file-20200917-18-u5zhop.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=574&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/358552/original/file-20200917-18-u5zhop.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=721&fit=crop&dpr=1 754w, https://images.theconversation.com/files/358552/original/file-20200917-18-u5zhop.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=721&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/358552/original/file-20200917-18-u5zhop.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=721&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">An effective citizens’ assembly would have participants from varying backgrounds and demographics, to be as inclusive as possible.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<h2>Evolving evidence</h2>
<p>A decade ago, the idea of citizens’ assemblies may have been dismissed by sceptics as pie in the sky. Here in Australia, the idea of a citizens’ assembly may have been tarnished by its identification with a partisan agenda, such as when former prime minister <a href="https://www.tandfonline.com/doi/full/10.1080/10361146.2013.786675?casa_token=nEsR3ITZtQ4AAAAA%3A3AQpuwuK34KX-XgyaQeItF4cLzAkaze3QS4v-S1yXq1B9w2BmN9ocI9L9KgmG2fCdrX9a8kRtyQjq1w">Julia Gillard</a> called for a citizens’ assembly on climate change. But today, citizens’ assemblies have begun to establish a credible track record.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/a-novel-idea-on-climate-change-ask-the-people-1962">A novel idea on climate change: ask the people</a>
</strong>
</em>
</p>
<hr>
<p>Last year, French President Emmanuel Macron invited 150 randomly selected citizens to consider ways to reduce the country’s carbon emissions by at least 40% within a decade. <a href="https://www.france24.com/en/20200622-french-citizens-council-on-the-environment-proposes-making-ecocide-illegal">Over nine months</a>, the assembly listened to more than 100 climate experts, with communications experts also on hand to help answer technical questions. </p>
<p>An assembly that included a 16-year-old student, a bus driver and a former fireman engaged in rigorous deliberation on the complex issues involved in ecological transition, even as a pandemic was unfolding. In the end, among other recommendations, the assembly endorsed making <a href="https://www.euronews.com/living/2020/06/25/france-wants-to-make-hurting-the-planet-illegal-but-what-is-ecocide">ecocide</a> a criminal act. Macron promised to put this recommendation to a national referendum.</p>
<p>There are many other examples of citizens’ assemblies that have contributed to enriching public conversations and policy-making. The Canadian province of British Columbia set up a <a href="https://participedia.net/case/1">Citizens’ Assembly on Electoral Reform</a> that successfully preceded a referendum. And the <a href="https://participedia.net/case/5316">Irish Citizens’ Assembly</a> on abortion and same-sex marriage informed a divisive debate about constitutional reform.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/fearmongering-is-scary-not-genetic-technologies-themselves-92171">Fearmongering is scary, not genetic technologies themselves</a>
</strong>
</em>
</p>
<hr>
<p>The stakes are high in the Global Citizens’ Assembly on Genome Editing. On the line are the legitimacy of policies and regulations based on the extent to which they reflect the values of ordinary citizens whose lives will potentially be affected by these technologies. </p>
<p>Beyond its impact on regulation, however, this democratic experiment can show the way on how citizens, scientists, and policymakers can talk about a fast-moving technology with more care, better information, and democratic deliberation.</p><img src="https://counter.theconversation.com/content/146398/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Nicole Curato receives funding from the Australian Research Council for project titled Global Citizen Deliberation: Analysing a Deliberative Documentary.</span></em></p><p class="fine-print"><em><span>Simon Niemeyer receives funding from the Australian Research Council for project titled Global Citizen Deliberation: Analysing a Deliberative Documentary.</span></em></p>Our approach to controversial technologies shouldn’t be guided by scientists alone, nor by peddlers of misinformation on social media. A citizens’ assembly could walk the line between the two.Nicole Curato, Associate Professor, Centre for Deliberative Democracy and Global Governance, University of CanberraSimon Niemeyer, Professor in Deliberative Democracy and Environmental Governance, University of CanberraLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1453672020-09-03T15:26:44Z2020-09-03T15:26:44ZCRISPR can help combat the troubling immune response against gene therapy<figure><img src="https://images.theconversation.com/files/356159/original/file-20200902-24-lmdp9z.jpg?ixlib=rb-1.1.0&rect=15%2C15%2C5176%2C5176&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Introducing healthy genes to replace defective ones is the essence of gene therapy.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/gene-therapy-royalty-free-image/574880295?adppopup=true">KTSFotos/Getty Images</a></span></figcaption></figure><p>One of the <a href="https://doi.org/10.1016/j.ymthe.2020.01.001">major challenges facing gene therapy</a> - a way to treat disease by replacing a patient’s defective genes with healthy ones - is that it is difficult to safely deliver therapeutic genes to patients without the immune system destroying the gene, and the vehicle carrying it, which can trigger life-threatening widespread inflammation.</p>
<p>Three decades ago researchers thought that gene therapy would be the ultimate treatment for genetically inherited diseases like <a href="https://ghr.nlm.nih.gov/condition/hemophilia">hemophilia</a>, <a href="https://www.nhlbi.nih.gov/health-topics/sickle-cell-disease">sickle cell anemia</a> and genetic diseases of metabolism. But the technology couldn’t dodge the immune response.</p>
<p>Since then, researchers have been looking for ways to perfect the technology and control immune responses to the gene or the vehicle. However, many of the strategies tested so far have <a href="https://www.sciencemag.org/news/2020/06/two-deaths-gene-therapy-trial-rare-muscle-disease">not been completely successful</a> <a href="https://www.sciencehistory.org/distillations/the-death-of-jesse-gelsinger-20-years-later">in overcoming this hurdle</a>. </p>
<p>Drugs that suppress the whole immune system, such as steroids, have been used to dampen the immune response when administering gene therapy. But it’s difficult to control when and where steroids work in the body, and they create unwanted side effects. My colleague <a href="http://www.ebrahimkhanilab.com">Mo Ebrahimkhani</a> and I wanted to tackle gene therapy with immune-suppressing tools that were easier to control.</p>
<p><a href="https://www.kianilab.com">I am a medical doctor and synthetic biologist</a> interested in gene therapy because six years ago my father was diagnosed with <a href="https://www.cancer.gov/types/pancreatic">pancreatic cancer</a>. Pancreatic cancer is one of the deadliest forms of cancer, and the current available therapeutics usually fail to save patients. As a result, novel treatments such as gene therapy might be the only hope.</p>
<p>Yet, many gene therapies fail because patients either already have pre-existing immunity to the vehicle used to introduce the gene or develop one in the course of therapy. This problem has plagued the field for decades, preventing the widespread application of the technology.</p>
<h2>Gene therapy: past and present</h2>
<p>Traditionally scientists use viruses - from which dangerous disease-causing genes have been removed - as vehicles to transport new genes to specific organs. These genes then produce a product that can compensate for the faulty genes that are inherited genetically. This is how gene therapy works. </p>
<p>Though there <a href="https://www.asgct.org/research/news/april-2020/world-hemophilia-day">have been examples</a> showing that <a href="https://www.labiotech.eu/medical/bluebird-bio-gene-therapy-thalassemia/">gene therapy was helpful</a> in some genetic diseases, they are still not perfect. Sometimes, a faulty gene is so big that you can’t simply fit the healthy replacement in the viruses commonly used in gene therapy.</p>
<p>Another problem is that when the immune system sees a virus, it assumes that it is a disease-causing pathogen and launches an attack to fight it off by producing antibodies and immune response – just as happens when people catch any other infectious viruses, like SARS-CoV-2 or the common cold. </p>
<p>Recently, though, with the rise of a <a href="https://www.sciencenewsforstudents.org/article/explainer-how-crispr-works">gene editing technology called CRISPR</a>, scientists can do gene therapy differently.</p>
<p>CRISPR can be used in many ways. In its primary role, it acts like a genetic surgeon with a sharp scalpel, enabling scientists to find a genetic defect and correct it within the native genome in desired cells of the organism. It can also repair more than one gene at a time. </p>
<p>Scientists can also use CRISPR to turn off a gene for a short period of time and then turn it back on, or vice versa, without permanently changing the letters of DNA that makes up or genome. This means that researchers like me can leverage CRISPR technology to revolutionize gene therapies in the coming decades.</p>
<p>But to use CRISPR for either of these functions, it still needs to be packaged into a virus to get it into the body. So some challenges, such as preventing the immune response to the gene therapy viruses, still need to be solved for CRISPR-based gene therapies. </p>
<p>Being trained as <a href="http://www.kianilab.com">a synthetic biologist</a>, I teamed up with Ebrahimkhani to use CRISPR to test whether we could shut down a gene that is responsible for immune response that destroys the gene therapy viruses. Then we investigated whether lowering the activity of the gene, and dulling the immune response, would allow the gene therapy viruses to be more effective.</p>
<p>[<em>Deep knowledge, daily.</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=deepknowledge">Sign up for The Conversation’s newsletter</a>.]</p>
<h2>Preventing the immune response that destroys gene therapy viruses</h2>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/356160/original/file-20200902-14-5r5jt3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/356160/original/file-20200902-14-5r5jt3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/356160/original/file-20200902-14-5r5jt3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=688&fit=crop&dpr=1 600w, https://images.theconversation.com/files/356160/original/file-20200902-14-5r5jt3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=688&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/356160/original/file-20200902-14-5r5jt3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=688&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/356160/original/file-20200902-14-5r5jt3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=864&fit=crop&dpr=1 754w, https://images.theconversation.com/files/356160/original/file-20200902-14-5r5jt3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=864&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/356160/original/file-20200902-14-5r5jt3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=864&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">CRISPR can precisely remove even single units of DNA.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/gene-editing-conceptual-illustration-royalty-free-illustration/1015902954?adppopup=true">KEITH CHAMBERS/SCIENCE PHOTO LIBRARY/Getty Images</a></span>
</figcaption>
</figure>
<p><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=MYD88">A gene called Myd88</a> is a key gene in the immune system and controls the response to bacteria and viruses, including the common gene therapy viruses. We decided to temporarily turn off this gene in the whole body of lab animals. </p>
<p>We injected animals with a collection of the CRISPR molecules that targeted the Myd88 gene and looked to see whether this reduced the quantity of antibodies that were produced to specifically fight our gene therapy viruses. We were excited to see that the animals that received our treatment using CRISPR produced less antibody against the virus.</p>
<p>This prompted us to ask what happens if we give the animal a second dose of the gene therapy virus. Usually the immune response against a gene therapy virus prevents the therapy from being administered multiple times. That’s because after the first dose, the immune system has seen the virus, and on the second dose, antibodies swiftly attack and destroy the virus before it can deliver its cargo.</p>
<p>We saw that animals receiving more than one dose did not show an increase in antibodies against the virus. And, in some cases, the effect of gene therapy improved compared with the animals in which we had not paused the Myd88 gene. </p>
<p>We also did a number of other experiments that proved that tweaking the Myd88 gene can be useful in fighting off other sources of inflammation. That could be useful in diseases like sepsis and even COVID-19. </p>
<p>While we are now beginning to improve this strategy in terms of controlling the activity of the Myd88 gene. Our results, now published in <a href="https://www.nature.com/articles/s41556-020-0563-3">Nature Cell Biology</a>,
provide a path forward to program our immune system during gene therapies and other inflammatory responses using the CRISPR technology.</p><img src="https://counter.theconversation.com/content/145367/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Samira Kiani is a co-founder and founding CSO of Safegen Therapeutics. She receives funding from National Institute of Health for her research program.</span></em></p>The immune system is trained to destroy viruses, even when they carry therapeutic cargo as is the case in gene therapy. Now researchers have figured out how to dial down the immune response.Samira Kiani, Associate Professor of Pathology, University of PittsburghLicensed as Creative Commons – attribution, no derivatives.