tag:theconversation.com,2011:/id/topics/crispr-15704/articlesCRISPR – The Conversation2024-03-27T19:07:40Ztag:theconversation.com,2011:article/2263932024-03-27T19:07:40Z2024-03-27T19:07:40ZThe first pig kidney has been transplanted into a living person. But we’re still a long way from solving organ shortages<figure><img src="https://images.theconversation.com/files/584634/original/file-20240327-22-zkx0ie.jpg?ixlib=rb-1.1.0&rect=0%2C73%2C8192%2C5383&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.massgeneral.org/news/press-release/worlds-first-genetically-edited-pig-kidney-transplant-into-living-recipient">Massachusetts General Hospital</a></span></figcaption></figure><p>In a world first, we heard last week that US surgeons had transplanted a kidney from a gene-edited pig into a living human. News reports said the procedure was <a href="https://www.npr.org/sections/health-shots/2024/03/21/1239790816/first-pig-kidney-human-transplant">a breakthrough</a> in xenotransplantation – when an organ, cells or tissues are transplanted from one species to another.</p>
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<figcaption><span class="caption">The world’s first transplant of a gene-edited pig kidney into a live human was announced last week.</span></figcaption>
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<p>Champions of xenotransplantation regard it as <em>the</em> solution to organ shortages across the world. In December 2023, <a href="https://www.anzdata.org.au/anzod/publications-2/organ-waiting-list/">1,445 people</a> in Australia were on the waiting list for donor kidneys. In the United States, more than <a href="https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/">89,000</a> are waiting for kidneys. </p>
<p>One biotech CEO says gene-edited pigs <a href="https://www.technologyreview.com/2015/08/12/248193/surgeons-smash-records-with-pig-to-primate-organ-transplants/">promise</a> “an unlimited supply of transplantable organs”.</p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6452271/">Not</a>, <a href="https://theconversation.com/organ-transplants-from-pigs-medical-miracle-or-pandemic-in-the-making-175290">everyone</a>, though, <a href="https://onlinelibrary.wiley.com/doi/10.1111/imj.13183">is convinced</a> transplanting animal organs into humans is really the answer to organ shortages, or even if it’s right to use organs from other animals this way.</p>
<p>There are two critical barriers to the procedure’s success: organ rejection and the transmission of <a href="https://journals.sagepub.com/doi/epdf/10.1177/09636897241226849">animal viruses to recipients</a>. </p>
<p>But in the past decade, a new platform and technique known as CRISPR/Cas9 – often shortened to CRISPR – has promised to mitigate these issues.</p>
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Read more:
<a href="https://theconversation.com/organ-transplants-from-pigs-medical-miracle-or-pandemic-in-the-making-175290">Organ transplants from pigs: Medical miracle or pandemic in the making?</a>
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<h2>What is CRISPR?</h2>
<p>CRISPR gene editing takes advantage of a system already found in nature. CRISPR’s “genetic scissors” evolved in bacteria and other microbes to help them fend off viruses. Their cellular machinery <a href="https://www.sciencedirect.com/science/article/pii/S0300908415001042#:%7E:text=The%20system%2C%20called%20CRISPR%2DCas,remember%2C%20recognize%20and%20clear%20infections.">allows them</a> to integrate and ultimately destroy viral DNA by cutting it.</p>
<p>In 2012, two teams of scientists <a href="https://www.science.org/doi/10.1126/science.1225829">discovered how to harness</a> this bacterial immune system. This is made up of repeating arrays of DNA and associated proteins, known as “Cas” (CRISPR-associated) proteins. </p>
<p>When they used a particular Cas protein (Cas9) with a “guide RNA” made up of a singular molecule, they found they could <a href="https://pubmed.ncbi.nlm.nih.gov/22745249/">program</a> the CRISPR/Cas9 complex to break and repair DNA at precise locations as they desired. The system could even “knock in” new genes at the repair site. </p>
<p>In 2020, the two scientists leading these teams were awarded a <a href="https://www.nobelprize.org/prizes/chemistry/2020/summary/">Nobel prize</a> for their work.</p>
<p>In the case of the latest xenotransplantation, CRISPR technology was used to <a href="https://www.massgeneral.org/news/press-release/worlds-first-genetically-edited-pig-kidney-transplant-into-living-recipient">edit 69 genes</a> in the donor pig to inactivate viral genes, “humanise” the pig with human genes, and knock out harmful pig genes.</p>
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<figcaption><span class="caption">How does CRISPR work?</span></figcaption>
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Read more:
<a href="https://theconversation.com/what-is-crispr-the-gene-editing-technology-that-won-the-chemistry-nobel-prize-147695">What is CRISPR, the gene editing technology that won the Chemistry Nobel prize?</a>
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<h2>A busy time for gene-edited xenotransplantation</h2>
<p>While CRISPR editing has brought new hope to the possibility of xenotransplantation, even recent trials show great caution is still warranted.</p>
<p>In 2022 and 2023, two patients with <a href="https://www.medschool.umaryland.edu/news/2023/um-medicine-faculty-scientists-and-clinicians-perform-second-historic-transplant-of-pig-heart-into-patient-with-end-stage-cardiovascular-disease.html#:%7E:text=The%20first%20historic%20surgery%2C%20performed,had%20end%2Dstage%20heart%20disease.">terminal heart diseases</a>, who were ineligible for traditional heart transplants, were granted <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00775-4/abstract">regulatory permission</a> to receive a gene-edited pig heart. These pig hearts had ten genome edits to make them more suitable for transplanting into humans. However, both patients died within several weeks of the procedures. </p>
<p>Earlier this month, we heard a team of surgeons in China transplanted a gene-edited pig liver into a <a href="https://www.nature.com/articles/d41586-024-00853-8">clinically dead man</a> (with family consent). The liver functioned well up until the ten-day limit of the trial.</p>
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Read more:
<a href="https://theconversation.com/you-donate-your-body-to-science-you-die-what-happens-next-1481">You donate your body to science, you die ... what happens next?</a>
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<h2>How is this latest example different?</h2>
<p>The gene-edited pig kidney <a href="https://www.massgeneral.org/news/kidney-xenotransplant-faqs">was transplanted</a> into a relatively young, living, legally competent and consenting adult.</p>
<p>The total number of gene edits edits made to the donor pig is very high. The researchers report making <a href="https://www.nature.com/articles/d41586-024-00879-y">69 edits</a> to inactivate viral genes, “humanise” the pig with human genes, and to knockout harmful pig genes.</p>
<p>Clearly, the race to transform these organs into viable products for transplantation is ramping up.</p>
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Read more:
<a href="https://theconversation.com/what-are-uterus-transplants-who-donates-their-uterus-and-what-are-the-risks-190443">What are uterus transplants? Who donates their uterus? And what are the risks?</a>
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<h2>From biotech dream to clinical reality</h2>
<p>Only a few months ago, CRISPR gene editing made its debut in mainstream medicine. </p>
<p>In November, drug regulators in the <a href="https://www.gov.uk/government/news/mhra-authorises-world-first-gene-therapy-that-aims-to-cure-sickle-cell-disease-and-transfusion-dependent-thalassemia">United Kingdom</a> and <a href="https://www.fda.gov/media/174618/download?attachment">US</a> approved the world’s first CRISPR-based genome-editing therapy for human use – a treatment for life-threatening forms of sickle-cell disease. </p>
<p>The treatment, known as <a href="https://sicklecellanemianews.com/ctx001-sickle-cell-disease">Casgevy</a>, uses CRISPR/Cas-9 to edit the patient’s own blood (bone-marrow) stem cells. By disrupting the <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2029392">unhealthy gene</a> that gives red blood cells their “sickle” shape, the aim is to produce red blood cells with a healthy spherical shape. </p>
<p>Although the treatment uses the patient’s own cells, the same underlying principle applies to recent clinical xenotransplants: unsuitable cellular materials may be edited to make them therapeutically beneficial in the patient.</p>
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<a href="https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Sickle cells have a different shape to healthy round red blood cells" src="https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=337&fit=crop&dpr=1 600w, https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=337&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=337&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">CRISPR technology is aiming to restore diseased red blood cells to their healthy round shape.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-rendered-medical-illustration-sickle-cell-2221001799">Sebastian Kaulitzki/Shutterstock</a></span>
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Read more:
<a href="https://theconversation.com/organs-too-risky-to-donate-may-be-safer-than-we-think-we-crunched-the-numbers-and-heres-what-we-found-124993">Organs 'too risky' to donate may be safer than we think. We crunched the numbers and here's what we found</a>
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<h2>We’ll be talking more about gene-editing</h2>
<p>Medicine and gene technology regulators are increasingly asked to <a href="https://www.utas.edu.au/__data/assets/pdf_file/0011/1634258/OP12-final-report.pdf">approve new experimental trials</a> using gene editing and CRISPR.</p>
<p>However, neither xenotransplantation nor the therapeutic applications of this technology lead to changes to the genome that can be inherited.</p>
<p>For this to occur, CRISPR edits would need to be applied to the cells at the earliest stages of their life, such as to <a href="https://doi.org/10.1089/crispr.2020.0082">early-stage embryonic cells</a> in vitro (in the lab). </p>
<p>In Australia, intentionally creating heritable alterations to the human genome is a criminal offence carrying <a href="https://classic.austlii.edu.au/au/legis/cth/consol_act/pohcfra2002465/s15.html">15 years’ imprisonment</a>. </p>
<p><a href="https://www.utas.edu.au/__data/assets/pdf_file/0011/1634258/OP12-final-report.pdf">No jurisdiction in the world</a> has laws that <a href="https://doi.org/10.1089/crispr.2020.0082">expressly permits</a> heritable human genome editing. However, some <a href="https://crispr-gene-editing-regs-tracker.geneticliteracyproject.org/russia-germline-embryonic/">countries</a> lack specific regulations about the procedure.</p>
<h2>Is this the future?</h2>
<p>Even without creating inheritable gene changes, however, xenotransplantation using CRISPR is in its infancy.</p>
<p>For all the promise of the headlines, there is not yet one example of a stable xenotransplantation in a living human lasting <a href="https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.03060/full">beyond seven months</a>. </p>
<p>While authorisation for this recent US transplant has been granted under the so-called “compassionate use” <a href="https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=312.310">exemption</a>, conventional clinical trials of pig-human xenotransplantation have yet to commence. </p>
<p>But the prospect of such trials would likely require significant improvements in current outcomes to gain regulatory approval <a href="https://www.fda.gov/media/102126/download">in the US</a> or <a href="https://iris.who.int/bitstream/handle/10665/341817/WHO-HTP-EHT-CPR-2011.01-eng.pdf?sequence=1&isAllowed=y">elsewhere</a>. </p>
<p>By the same token, regulatory approval of any “off-the-shelf” xenotransplantation organs, including gene-edited kidneys, would seem <a href="https://link.springer.com/chapter/10.1007/978-981-99-7691-1_24">some way off</a>.</p><img src="https://counter.theconversation.com/content/226393/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Christopher Rudge was a member of a research team that designed and convened an Australian citizens' jury on genome editing in 2021-22. This was funded by the Medical Research Future Fund.</span></em></p>Champions of xenotransplantation see it as the solution to organ shortages across the world. But this technology has other applications.Christopher Rudge, Law lecturer, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2196832024-02-05T23:06:31Z2024-02-05T23:06:31ZGenetic diseases: How scientists are working to make DNA repair (almost) a piece of cake<figure><img src="https://images.theconversation.com/files/564984/original/file-20231101-27-722eas.jpg?ixlib=rb-1.1.0&rect=5%2C0%2C992%2C561&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">An error in DNA is called a mutation.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>I have always been fascinated by genetics, a branch of biology that helps explain everything from the striking resemblance between different members of a family to the fact that strawberry plants are frost-resistant. It’s an impressive field!</p>
<p>I also have a personal connection to genetics. Growing up, I learned that members of my family had a form of <a href="https://doi.org/10.3390/jcm12186011">muscular dystrophy</a> called dysferlinopathy. I watched as my mother gradually lost the ability to climb stairs and had to use a cane, then a walker, and finally a wheelchair to get around. Her leg muscles were less and less able to repair themselves and became weaker with time.</p>
<p>My parents explained to me that all these changes were due to the error of a single letter among the billions of letters in a long DNA sequence. This error prevents the production of the protein <a href="https://doi.org/10.3390/jcm12144769">responsible for repairing arm and leg muscles</a>.</p>
<p>Today, I am a doctoral research student in molecular medicine. I study the treatment of hereditary diseases in order to be able to help families like my own. In this article, I will demystify hereditary diseases and show what research is being carried out to treat them.</p>
<h2>A piece of cake? Not quite</h2>
<p>Let’s start by imagining DNA as a recipe book. Each gene represents a different recipe. The page with the chocolate cake recipe has a nice picture, but there is some information missing. The recipe says to preheat the oven and measure the flour, but the rest of the page is torn. So it is impossible to make the cake. We go ahead and serve our meal made from all the other recipes, but there is no chocolate cake even though this is a particularly important part of the meal.</p>
<p>The same is true for hereditary diseases. In this case, the body can make all the proteins it needs except one. In dysferlinopathy, which affects my family, the missing recipe is the protein that repairs the muscles of the arms and legs. Each hereditary disease has its own damaged page in its recipe book.</p>
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<img alt="" src="https://images.theconversation.com/files/580032/original/file-20240305-21577-nvf7ba.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/580032/original/file-20240305-21577-nvf7ba.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=426&fit=crop&dpr=1 600w, https://images.theconversation.com/files/580032/original/file-20240305-21577-nvf7ba.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=426&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/580032/original/file-20240305-21577-nvf7ba.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=426&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/580032/original/file-20240305-21577-nvf7ba.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=535&fit=crop&dpr=1 754w, https://images.theconversation.com/files/580032/original/file-20240305-21577-nvf7ba.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=535&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/580032/original/file-20240305-21577-nvf7ba.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=535&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">A mutation can cause the absence of a protein that has its own function.</span>
<span class="attribution"><span class="source">(Camille Bouchard)</span>, <span class="license">Fourni par l'auteur</span></span>
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<p>To be precise, an error in the DNA is called a mutation. There are different types of mutations. Some are caused by adding letters, like adding an ingredient to the recipe. This addition could lead to a delicious chocolate cake with strawberries, or to a cake that is no longer edible because we added motor oil to it.</p>
<p>Other mutations are caused by the removal (or elimination) of one or more letters (or ingredients), or by substitutions that replace one letter with another. All of these modifications can lead to favourable or non-impactful changes, such as the appearance of the first blue eyes in evolution, or the ability to breathe outside of water. But these modifications can also bring about unfavourable results, such as a hereditary disease or cancer.</p>
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<a href="https://images.theconversation.com/files/565888/original/file-20231214-19-3u3el2.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/565888/original/file-20231214-19-3u3el2.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/565888/original/file-20231214-19-3u3el2.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=616&fit=crop&dpr=1 600w, https://images.theconversation.com/files/565888/original/file-20231214-19-3u3el2.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=616&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/565888/original/file-20231214-19-3u3el2.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=616&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/565888/original/file-20231214-19-3u3el2.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=774&fit=crop&dpr=1 754w, https://images.theconversation.com/files/565888/original/file-20231214-19-3u3el2.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=774&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/565888/original/file-20231214-19-3u3el2.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=774&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">There are different types of mutations.</span>
<span class="attribution"><span class="source">(Camille Bouchard)</span>, <span class="license">Fourni par l'auteur</span></span>
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<h2>Repairing DNA</h2>
<p>From a young age, I understood that my mother was sick due to the error of a gene, but that I would not develop the disease because my father did not have the same error. This is called a recessive disease, since there must be an error in the gene of each of the two parents in order for the disease to manifest. Other hereditary diseases are dominant, meaning that a mutation in the DNA passed down from just one parent is enough to impair the production of a protein.</p>
<p>As part of my research, I look at the DNA sequence of each dysferlinopathy patient to see where the error is.</p>
<p>To try to correct it, I use <a href="https://doi.org/10.3390/cells12040536">Prime editing</a>, a technique which makes it possible to cut the DNA near the mutation and rewrite the sequence correctly. Prime editing is a version of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4975809/">CRISPR-Cas9</a>, a technique that allows DNA to be cut at a particular location.</p>
<p>Prime editing uses a protein called Cas9, which occurs naturally in bacteria. This protein allows bacteria to destroy the DNA sequences of viruses that could infect them. The mission of the Cas9 protein is to recognize a sequence and cut it.</p>
<p>When we use Cas9 in our human cells, we attach it to another protein, which rewrites the DNA sequence based on a template. In other words, we give the cell an error-free sequence so that it can go ahead and manufacture the protein on its own. It’s a bit like recovering the original page of the recipe book so you can finally serve the chocolate cake.</p>
<h2>A step in the right direction</h2>
<p>So why aren’t we hearing about Prime editing, when it could be used to treat a variety of diseases? Because the technology is not yet fully developed. At the moment we are able to repair DNA directly in cells in the laboratory, but we lack the means to deliver the two large proteins (Cas9 and the one that rewrites) to the cells to be treated (for example, to the centre of the affected muscles).</p>
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<span class="caption">Prime editing is a technique being studied to correct mutations in different genes.</span>
<span class="attribution"><span class="source">(Camille Bouchard)</span>, <span class="license">Fourni par l'auteur</span></span>
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</figure>
<p>In other words, we have found the chocolate cake recipe, but it’s written on a page that is too large to fit in an email or put in an envelope. Many laboratories, including mine, are looking for an efficient and safe vehicle that will be able to deliver these proteins.</p><img src="https://counter.theconversation.com/content/219683/count.gif" alt="La Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Camille Bouchard received funding from the Jain Foundation and the Fondation du CHU de Québec.</span></em></p>Many people know someone with a genetic disease, but few understand how gene mutations work.Camille Bouchard, Étudiante au doctorat en médecine moléculaire (correction génétique de maladies héréditaires), Université LavalLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2195722023-12-14T13:10:22Z2023-12-14T13:10:22ZCRISPR and other new technologies open doors for drug development, but which diseases get prioritized? It comes down to money and science<figure><img src="https://images.theconversation.com/files/565611/original/file-20231213-19-56i402.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2070%2C1449&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">So many diseases to treat, so little money and time.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/covid-19-vaccine-loop-royalty-free-image/1288570747">Andriy Onufriyenko/Moment via Getty Images</a></span></figcaption></figure><p>Prescription drugs and vaccines revolutionized health care, dramatically decreasing death from disease and improving quality of life across the globe. But how do researchers, universities and hospitals, and the pharmaceutical industry decide which diseases to pursue developing drugs for?</p>
<p>In <a href="https://scholar.google.com/citations?user=lWAD9d8AAAAJ&hl=en">my work</a> as director of the <a href="https://pharmacy.uconn.edu/hopes/">Health Outcomes, Policy, and Evidence Synthesis</a> group at the University of Connecticut School of Pharmacy, I assess the effectiveness and safety of different treatment options to help clinicians and patients make informed decisions. My colleagues and I study ways to create new drug molecules, deliver them into the body and improve their effectiveness while reducing their potential harms. Several factors determine which avenues of drug discovery that people in research and pharmaceutical companies focus on.</p>
<h2>Funding drives research decisions</h2>
<p>Research funding amplifies the pace of scientific discovery needed to create new treatments. Historically, <a href="https://doi.org/10.1001/jamahealthforum.2023.1921">major supporters of research</a> like the National Institutes of Health, pharmaceutical industry and private foundations funded studies on the most common conditions, like heart disease, diabetes and mental health disorders. A <a href="https://doi.org/10.18553%2Fjmcp.2022.28.7.732">breakthrough therapy</a> would help millions of people, and a small markup per dose would generate hefty profits.</p>
<p>As a consequence, research on rare diseases was not well-funded for decades because it would help fewer people and the costs of each dose had to be very high to turn a profit. Of the <a href="https://www.fda.gov/patients/rare-diseases-fda">more than 7,000 known rare diseases</a>, defined as <a href="https://rarediseases.info.nih.gov/about">fewer than 200,000 people affected</a> in the U.S., <a href="https://www.ncbi.nlm.nih.gov/books/NBK56187/">only 34 had a therapy approved</a> by the Food and Drug Administration before 1983.</p>
<p>The passage of the <a href="https://doi.org/10.1371%2Fjournal.pmed.1002191">Orphan Drug Act</a> changed this trend by offering tax credits, research incentives and prolonged patent lives for companies actively developing drugs for rare diseases. From 1983 to 2019, <a href="https://doi.org/10.1186/s13023-021-01901-6">724 drugs</a> were approved for rare diseases.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/565616/original/file-20231213-27-em9ehu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Person sluicing a bucket of ice water over another person's head" src="https://images.theconversation.com/files/565616/original/file-20231213-27-em9ehu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/565616/original/file-20231213-27-em9ehu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/565616/original/file-20231213-27-em9ehu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/565616/original/file-20231213-27-em9ehu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/565616/original/file-20231213-27-em9ehu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/565616/original/file-20231213-27-em9ehu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/565616/original/file-20231213-27-em9ehu.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 viral ALS ice bucket challenge in 2014 was a fundraising success.</span>
<span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/IceBucketChallenge/4dd78b9ab4044aef8a09a6f7d688b168">Elise Amendola/AP Photo</a></span>
</figcaption>
</figure>
<p>Emerging social issues or opportunities can significantly affect funding available to develop drugs for certain diseases. When COVID-19 raged across the world, funding from <a href="https://www.nationaldefensemagazine.org/articles/2023/9/19/learning-lessons-from-mrap-operation-warp-speed">Operation Warp Speed</a> led to vaccine development in record time. Public awareness campaigns such as the <a href="https://www.npr.org/2022/10/01/1126397565/the-ice-bucket-challenge-wasnt-just-for-social-media-it-helped-fund-a-new-als-dr">ALS ice bucket challenge</a> can also directly raise money for research. This viral social media campaign provided 237 scientists <a href="https://www.als.org/stories-news/ice-bucket-challenge-dramatically-accelerated-fight-against-als#">nearly US$90 million</a> in research funding from 2014 to 2018, which led to the discovery of five genes connected to amyotrophic lateral sclerosis, commonly called Lou Gehrig’s disease, and new clinical trials.</p>
<h2>How science approaches drug development</h2>
<p>To create breakthrough treatments, researchers need a basic understanding of what disease processes they need to enhance or block. This requires developing <a href="https://doi.org/10.1002/jcph.1569">cell and</a> <a href="https://theconversation.com/expanding-alzheimers-research-with-primates-could-overcome-the-problem-with-treatments-that-show-promise-in-mice-but-dont-help-humans-188207">animal models</a> that can simulate human biology. </p>
<p>It can <a href="https://www.fda.gov/drugs/development-approval-process-drugs">take many years</a> to vet potential treatments and develop the finished drug product ready for testing in people. Once scientists identify a potential biological target for a drug, they use <a href="https://theconversation.com/discovering-new-drugs-is-a-long-and-expensive-process-chemical-compounds-that-dupe-screening-tools-make-it-even-harder-175972">high-throughput screening</a> to rapidly assess hundreds of chemical compounds that may have a desired effect on the target. They then modify the most promising compounds to enhance their effects or reduce their toxicity. </p>
<p>When these compounds have lackluster results in the lab, companies are likely to <a href="https://doi.org/10.1186%2Fs12967-016-0838-4">halt development</a> if the estimated potential revenue from the drug is less than the estimated cost to improve the treatments. Companies can charge more money for drugs that <a href="https://digital.kwglobal.com/publication/?i=456831&p=13&view=issueViewer&pp=1">dramatically reduce deaths or disability</a> than for those that only reduce symptoms. And researchers are more likely to continue working on drugs that have a greater potential to help patients. In order to obtain FDA approval, companies ultimately need to show that the drug causes more benefits for patients than harms. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/2sAGtqm3o1g?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Casgevy, a CRISPR-based treatment for sickle cell anemia, is considered a milestone in gene therapy.</span></figcaption>
</figure>
<p>Sometimes, researchers know a lot about a disease, but available technology is insufficient to produce a successful drug. For a long time, scientists knew that <a href="https://doi.org/10.1056/NEJMoa2031054">sickle cell disease</a> results from a defective gene that leads cells in the bone marrow to produce poorly formed red blood cells, causing severe pain and blood clots. Scientists lacked a way to fix the issue or to work around it with existing methods. </p>
<p>However, in the early 1990s, basic scientists discovered that bacterial cells have a mechanism to <a href="https://theconversation.com/human-genome-editing-offers-tantalizing-possibilities-but-without-clear-guidelines-many-ethical-questions-still-remain-200983">identify and edit DNA</a>. With that model, researchers began painstaking work developing a <a href="https://www.broadinstitute.org/what-broad/areas-focus/project-spotlight/crispr-timeline">technology called CRISPR</a> to identify and edit genetic sequences in human DNA. </p>
<p>The technology finally progressed to the point where scientists were able to successfully target the problematic gene in patients with sickle cell and edit it to produce normally functioning red blood cells. In December 2023, <a href="https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease">Casgevy became the first CRISPR-based drug</a> approved by the FDA.</p>
<p>Sickle cell disease made a great target for this technology because it was caused by a single genetic issue. It was also an attractive disease to focus on because it affects around 100,000 people in the U.S. and is <a href="https://doi.org/10.2147/ijgm.s257340">costly to society</a>, causing many hospitalizations and lost days of work. It also <a href="https://theconversation.com/sickle-cell-disease-can-be-deadly-and-the-persistent-health-inequities-facing-black-americans-worsen-the-problem-212434">disproportionately affects Black Americans</a>, a population that has been <a href="https://theconversation.com/yes-black-patients-do-want-to-help-with-medical-research-here-are-ways-to-overcome-the-barriers-that-keep-clinical-trials-from-recruiting-diverse-populations-185337">underrepresented in medical research</a>.</p>
<h2>Real-world drug development</h2>
<p>To put all these pieces of drug development into perspective, consider the <a href="https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm">leading cause of death in the U.S.</a>: cardiovascular disease. Even though there are several drug options available for this condition, there is an ongoing need for more effective and less toxic drugs that reduce the risk of heart attacks and strokes. </p>
<p>In 1989, epidemiologists found that patients with <a href="https://doi.org/10.1001/jama.300.11.1343">higher levels of bad, or LDL, cholesterol</a> had more heart attacks and strokes than those with lower levels. Currently, <a href="https://www.cdc.gov/cholesterol/facts.htm#">86 million American adults</a> have elevated cholesterol levels that can be treated with drugs, like the popular statins Lipitor (atorvastatin) or Crestor (rosuvastatin). However, <a href="https://www.pharmacypracticenews.com/Clinical/Article/06-22/Using-National-Guidelines-to-Determine-Hyperlipidemia-Treatment/67209">statins alone</a> cannot get everyone to their cholesterol goals, and many patients develop unwanted symptoms limiting the dose they can receive.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/565617/original/file-20231213-14492-77b8o9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Two blister packs of burnt orange pills with days of the week listed on each dose" src="https://images.theconversation.com/files/565617/original/file-20231213-14492-77b8o9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/565617/original/file-20231213-14492-77b8o9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=386&fit=crop&dpr=1 600w, https://images.theconversation.com/files/565617/original/file-20231213-14492-77b8o9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=386&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/565617/original/file-20231213-14492-77b8o9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=386&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/565617/original/file-20231213-14492-77b8o9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=485&fit=crop&dpr=1 754w, https://images.theconversation.com/files/565617/original/file-20231213-14492-77b8o9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=485&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/565617/original/file-20231213-14492-77b8o9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=485&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">There are several statins on the market to treat high cholesterol levels.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/daily-statin-dose-royalty-free-image/643755285">Peter Dazeley/The Image Bank via Getty Images</a></span>
</figcaption>
</figure>
<p>So scientists developed models to understand how LDL cholesterol is created in and removed from the body. They found that LDL receptors in the liver removed bad cholesterol from the blood, but a <a href="https://doi.org/10.1177/1074248418769040">protein called PCSK9</a> prematurely destroys them, boosting bad cholesterol levels in the blood. This led to the development of the drugs <a href="https://doi.org/10.1177/1074248418769040">Repathy (evolocumab) and Praluent (alirocumab)</a> that bind to PCSK9 and stop it from working. Another drug, <a href="https://doi.org/10.1002/jcph.2045">Leqvio (inclisiran)</a>, blocks the genetic material coding for PCSK9. </p>
<p>Researchers are also developing a <a href="https://www.pharmacypracticenews.com/Online-First/Article/12-23/Novel-Gene-Therapy-Slashes-LDL-in-Patients-With-Hypercholesterolemia/72152">CRISPR-based method</a> to more effectively treat the disease.</p>
<h2>The future of drug development</h2>
<p>Drug development is driven by the priorities of their funders, be it governments, foundations or the pharmaceutical industry. </p>
<p>Based on the market, companies and researchers tend to study highly prevalent diseases with devastating societal consequences, such as <a href="https://pubmed.ncbi.nlm.nih.gov/33756057/">Alzheimer’s disease</a> and <a href="https://www.cdc.gov/opioids/data/index.html">opioid use disorder</a>. But the work of advocacy groups and foundations can enhance research funding for other specific diseases and conditions. Policies like the Orphan Drug Act also create successful incentives to discover treatments for rare diseases. </p>
<p>However, in 2021, 51% of drug discovery spending in the U.S. was directed at <a href="https://www.evernorth.com/articles/specialty-drug-trends-and-utilization">only 2% of the population.</a>. How to strike a balance between providing incentives to develop <a href="https://theconversation.com/the-price-of-a-miracle-should-we-limit-spending-on-lifesaving-drugs-79609">miracle drug therapies</a> for a few people at the expense of the many is a question researchers and policymakers are still grappling with.</p><img src="https://counter.theconversation.com/content/219572/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>C. Michael White 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>Drug development takes a great deal of time, money and effort. While future profits play a big factor in which diseases gets prioritized, advocacy and research incentives can also tilt the scale.C. Michael White, Distinguished Professor of Pharmacy Practice, University of ConnecticutLicensed 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/2014062023-03-24T09:34:57Z2023-03-24T09:34:57ZCOVID testing led to new techniques of disease diagnosis: progress mustn’t stop now<figure><img src="https://images.theconversation.com/files/514637/original/file-20230310-142-f88cb4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Covid-19 exposed critical shortcomings of existing diagnostic techniques</span> <span class="attribution"><span class="source">Michael Tewelde/Xinhua via Getty Images</span></span></figcaption></figure><p>In March 2020, weeks before the World Health Organization (WHO) declared COVID-19 a pandemic, its director-general Tedros Adhanom Ghebreyesus delivered <a href="https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---16-march-2020">a speech</a> in which he emphasised the importance of testing:</p>
<blockquote>
<p>… the most effective way to prevent infections and save lives is breaking the chains of transmission. And to do that, you must test and isolate. You cannot fight a fire blindfolded. And we cannot stop this pandemic if we don’t know who is infected. We have a simple message for all countries: test, test, test.</p>
</blockquote>
<p>The pandemic exposed critical shortcomings of existing diagnostic techniques. It revealed an urgent need for tests that are faster, simpler, cheaper and more scalable than existing methods, and just as accurate. </p>
<p>Three years on, the global face of diagnostics has changed. New techniques of disease diagnosis have been developed that can be applied to other emerging zoonotic pathogens such as “<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367867/">disease X</a>” – a hypothetical infectious disease that has the potential to develop into a pandemic.</p>
<p>As a molecular scientist with a keen interest in veterinary disease diagnostics, I have closely followed developments in the diagnostic space since the start of the pandemic. These emerging technologies, together with conventional tests, have the potential to overcome bottlenecks in the current diagnostic procedures. By incorporating these tests into a country’s healthcare system, clinicians and policy makers are better equipped to practise precision medicine and to react to potential outbreaks.</p>
<h2>How the tests changed</h2>
<p>The first diagnostic tests for SARS-CoV-2 (the virus that causes COVID disease) used established molecular techniques such as reverse transcription polymerase reaction (RT-PCR). These techniques detect and identify organisms by amplifying their genetic material millions of times. Running the tests however requires trained technicians and expensive equipment.</p>
<p>As the pandemic became more severe, other ways to test for the virus had to be developed. Substances and compounds needed to effectively run diagnostic tests were in short supply and many countries did not have the kinds of sophisticated laboratories needed for the existing tests. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178421/">Low- and middle-income countries</a> like those throughout the African continent had limited finances too and not enough trained specialists to handle the demand.</p>
<p>Isothermal amplification techniques helped to address the need. This is a simple process which rapidly and effectively amplifies DNA and RNA (genetic material) at constant temperature. </p>
<p>Immunological assays also helped. These tests can be used on-site or in the lab and are able to detect specific molecules such as antibodies and antigens. Antibodies are generated in a person’s body when a foreign molecule (antigen) invades the body.</p>
<p>These cost-effective tests provide rapid results and can be used on a big scale even where resources are scarce. The <a href="https://www.mdpi.com/2075-4418/11/2/182">major challenge</a> of these tests is that they are less accurate. Unlike molecular tests, which amplify the genetic material of the virus, immunological assays do not amplify their protein signal. This makes them <a href="https://www.science.org/content/article/coronavirus-antigen-tests-quick-and-cheap-too-often-wrong">less sensitive</a>. The risk is high that an infected person might incorrectly be told that they don’t have the virus.</p>
<p>The global diagnostic community realised it was time to look at methods that were as accurate as conventional molecular tests but could be used outside laboratories and on a large scale. </p>
<h2>Big strides</h2>
<p>Scientists needed a new generation of rapid, accurate, accessible and affordable diagnostic tests. The National Institutes of Health in the US set up the Rapid Acceleration of Diagnostics programme (<a href="https://www.nih.gov/research-training/medical-research-initiatives/radx/radx-programs">RADx</a>) in 2020 to fund innovative point-of-care and home-based tests and to speed up the development, validation and commercialisation of these tests.</p>
<p>One particularly interesting change in this space is the use of <a href="https://www.sciencedirect.com/science/article/pii/S1046202321000992">CRISPR</a>. The technology was previously known for its use in gene editing. But now it has revolutionised diagnostics with the launch of SHERLOCK and DETECTR, two innovative CRISPR-based kits used for the detection of SARS-CoV-2. These are particularly sensitive and specific and provide a visual colour readout using a commercially available paper dipstick, making them suitable for use as a point-of-care test. </p>
<p>The versatility of these techniques enables researches to apply the same principles to the detection of other infectious diseases too.</p>
<p>There have also been advances in using <a href="https://www.mdpi.com/1467-3045/44/10/325">biosensors</a>, <a href="https://luminostics.com/">nanotechnology</a>, <a href="https://nicoyalife.com/blog/nicoya-covid-19-diagnostic-test-2/?utm_campaign=COVID-19">smartphone-based tests</a> and <a href="https://www.nature.com/articles/s41591-020-1123-x">wearable technologies</a> for diagnostics.</p>
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Read more:
<a href="https://theconversation.com/what-is-crispr-the-gene-editing-technology-that-won-the-chemistry-nobel-prize-147695">What is CRISPR, the gene editing technology that won the Chemistry Nobel prize?</a>
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<p>Overall, in the past three years, the <a href="https://pubs.rsc.org/en/content/articlelanding/2023/lc/d2lc00662f">focus of disease testing</a> has moved from simple detecting and understanding to incorporating speed, efficiency and portability of the tests.</p>
<h2>Problems remain</h2>
<p>While there is a lot to celebrate in the diagnostic space, problems remain. There are barriers in developing and disseminating tests, particularly in poorer countries. <a href="https://www.finddx.org/wp-content/uploads/2022/12/20221210_rep_democratizing_testing_FV_EN.pdf">Fairer</a> access to quality testing and improved data sharing between countries is needed to eliminate the inequity in diagnostics.</p>
<p>The lack of resources to deliver a robust regulatory system in low- and middle-income countries also poses a serious challenge. Companies have less incentive to develop and commercialise products where there is weak regulation. Thus countries still depend on tests that are manufactured elsewhere. </p>
<p>As the world moves out of its pandemic response phase, it is likely that investment in diagnostics will fall. With a reduced need for tests, the economic return of investing in developing tests will diminish.</p>
<p>This is unfortunate as there are still so many healthcare challenges worldwide and unless disease surveillance is proactive, it won’t be possible to predict where the next pandemic might emerge from. The momentum created by the COVID pandemic offers an opportunity and should be used to build on the things that worked well in the diagnostic industry and to improve on the things that didn’t.</p><img src="https://counter.theconversation.com/content/201406/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Angelika Loots 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 pandemic spurred the diagnostics industry to consider aspects like scale, affordability, speed and portability of tests.Angelika Loots, Postdoctoral Fellow, University of PretoriaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2012342023-03-10T22:42:38Z2023-03-10T22:42:38ZSomatic genome editing therapies are becoming a reality – but debate over ethics, equitable access and governance continue<figure><img src="https://images.theconversation.com/files/514625/original/file-20230310-30-d4sd7f.jpg?ixlib=rb-1.1.0&rect=0%2C51%2C5760%2C3181&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Sangharsh Lohakare / Unsplash</span></span></figcaption></figure><p>Hundreds of experts from around the world gathered at the Francis Crick Institute in London this week for the Third International Summit on Human Genome Editing.</p>
<p>As at the first and second summits, held in Washington DC in 2015 and Hong Kong in 2018, leading experts in research shared their discoveries and discussed how they should be used. </p>
<p>The prospect of curing certain diseases by changing the parts of our DNA that cause them is becoming a reality. A somatic genome editing treatment for sickle cell disease is set to obtain <a href="https://www.barrons.com/articles/crispr-therapeutics-stock-fda-sickle-cell-gene-therapy-bf56a18c">regulatory approval</a> in the US later this year.</p>
<p>“Delivery” was a recurring issue: the delivery of equitable access to genome editing therapies, ongoing research to optimise delivery systems for genome editing apparatus and delivery of measures to foster discussions regarding regulation, governance, public and patient engagement.</p>
<p>American Nobel laureate David Baltimore aptly noted in his opening remarks, “new technologies continue to challenge our society”. The advent of CRISPR gene-editing technology, short for “Clustered Regularly Interspaced Short Palindromic Repeats”, has reaffirmed this proposition, igniting a global dialogue on its accompanying ethical and regulatory issues. </p>
<p>Five years after the last summit, CRISPR technology has continued to mature. It is an insurmountable task to capture all of the developments in both the science and ethics of CRISPR technology. These will be addressed with reference to the key themes raised during the summit – scientific developments, accessibility and the importance of public and patient engagement. </p>
<h2>Scientific developments</h2>
<p>Many new advances in genome editing techniques were presented. </p>
<p>American chemist and biologist David Liu reported on findings to use “<a href="https://www.nature.com/articles/d41587-019-00032-5">prime editing</a>” to treat genetic conditions such as Huntington’s disease and Friedreich’s ataxia. Unlike CRISPR, which makes a double stranded cut in the DNA, prime editing induces a single stranded cut. This makes it more versatile and precise for targeted deletion and insertion of genetic sequences.</p>
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<a href="https://theconversation.com/what-is-gene-editing-and-how-could-it-shape-our-future-199025">What is gene editing and how could it shape our future?</a>
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<p>The summit heard about Vertex Pharmaceutical’s CRISPR-based treatment for sickle cell disease. The treatment is <a href="https://www.statnews.com/2023/03/07/crispr-sickle-cell-access/">expected</a> to become the first approved CRISPR genome editing therapy later this year.</p>
<p>There were also reports of research using CRISPR technology to treat diseases including Duchenne muscular dystrophy, cancer, HIV/AIDS, heart and muscle disease and inborn errors of immunity. American molecular biologist Eric Olson reported success in using base editing to <a href="https://www.science.org/doi/10.1126/science.ade1105">target CaMKIIδ</a>, a central regulator of cardiac signalling, in restoring cardiac function, as a treatment for myocardial infarction. </p>
<h2>Equitable access</h2>
<p>As research proceeds and treatments become available, questions about equitable access to the technology arise.</p>
<p>Equity extends beyond considerations of cost, access and ownership, to research engagement and output. This refers to capacity for knowledge production, data sovereignty and collection, access to latest knowledge, opportunities for collaboration and infrastructure to facilitate recruitment and trialling of new therapies. </p>
<p>Access issues are particularly relevant to lower- and middle-income countries, which may be compromised by systemic and structural inequities. Policy and political landscapes, economic constraints and scientific racism further perpetuate this inequity. </p>
<p>Gautam Dongre, representing the National Alliance of Sickle Cell Organisations India, described the reality of those living with sickle cell disease in India, where access to treatment is dire: </p>
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<p>“Our priority is to be alive, to receive gene therapy in the future.”</p>
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<h2>Patient perspectives and public engagement</h2>
<p>The summit also gave a platform to the experiences and concerns of people with lived experience of genetic disease. This included insights into the role and utility of public engagement, such as patient advocacy groups, do-it-yourself community groups and citizens’ juries.</p>
<p>A memorable presentation from Victoria Gray – the first recipient of Vertex Pharmaceutical’s CRISPR therapy for sickle cell disease – highlighted its life-changing impact. Gray says her CRISPR-modified “super cells” have cured her, enabling her to lead a disease-free life. The great potential of CRISPR technology can be realised, but importantly, it must be accessible to all.</p>
<h2>Concluding remarks</h2>
<p>How should CRISPR technology be regulated? This is a critical question.</p>
<p>As the summit’s organisers <a href="https://royalsociety.org/-/media/events/2023/03/human-genome-editing-summit/statement-from-the-organising-committee-of-the-third-international-summit-on-human-genome-editing.pdf">noted</a>, somatic genome editing has made “remarkable progress”, demonstrating its capability to “cure once-incurable diseases”. Further research is needed to target more diseases and enhance our understanding of risks and unintended consequences.</p>
<p>“Somatic” genome editing (which makes changes that are not heritable) is different to germline and heritable genome editing (which makes heritable changes). </p>
<p>Basic research for germline genome editing, which is not for reproduction purposes, is underway, for example, in gametes and embryos to explore aspects of early development. However, the organising committee concluded that heritable human genome editing for reproduction purposes “remains unacceptable at this time”. This is in light of the absence of preclinical evidence for safety and efficacy, legal authorisation and rigorous oversight and governance.</p>
<p>The concept of “safe enough” was interrogated – whose ethics should be applied to make this value judgment? Does the notion of safety traverse into areas beyond medically defined risks of physical harm? </p>
<p>It is notable that risk tolerance and perception of safety is dictated by an individual’s position in their country, culture, socio-economic status and lived experience. </p>
<p>In 2021, the World Health Organization published <a href="https://www.who.int/publications/i/item/9789240030060">a framework for governing human genome editing</a>. This retains its authority as an exemplar for a pathway toward an appropriate regulatory framework. While not overly prescriptive, it was designed to be adaptable for implementation in any jurisdiction. This year, Uganda plans to implement the framework as a pilot project. </p>
<p>The organising committee called for global action to explore measures for equitable and affordable pathways to access genome editing therapies. Ongoing global discussions are far from complete, and perhaps may never be complete, reinforcing the need for collective dialogue to proceed this summit. <em>And on with research, innovation and collaboration</em>.</p><img src="https://counter.theconversation.com/content/201234/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Olga C. Pandos is a recipient of the Australian Government Research Training Program Scholarship.</span></em></p>At the Third International Summit on Human Genome Editing, experts gather to discuss the path forward for CRISPR and other gene-editing technologiesOlga C. Pandos, PhD Candidate in Technology, Medical Law and Ethics, University of AdelaideLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2009832023-03-08T12:06:26Z2023-03-08T12:06:26ZHuman genome editing offers tantalizing possibilities – but without clear guidelines, many ethical questions still remain<figure><img src="https://images.theconversation.com/files/513790/original/file-20230306-28-k1tc0y.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1936%2C1547&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">DNA editing has the capacity to treat many diseases, but how to do this safely and equitably remains unclear.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/molecules-illustration-royalty-free-image/1148113002">KTSDESIGN/Science Photo Library via Getty Images</a></span></figcaption></figure><p><a href="https://royalsociety.org/science-events-and-lectures/2023/03/2023-human-genome-editing-summit/">The Third International Summit on Human Genome Editing</a>, a three-day conference organized by the Royal Society, the U.K. Academy of Medical Sciences, the U.S. National Academies of Sciences and Medicine and The World Academy of Sciences, was held this week in March 2023 at the Francis Crick Institute in London. Scientists, bioethicists, physicians, patients and others gathered to discuss the latest developments on this technology that lets researchers modify DNA with precision. And a major topic at the summit was <a href="https://royalsociety.org/-/media/events/2023/03/human-genome-editing-summit/third-international-summit-on-human-genome-editing-programme-booklet.pdf?la=en-GB&hash=16DB894FBD02A549B2F090D575C3E92D">how to enforce</a> research policies and ethical principles for human genome editing.</p>
<p>One of the first agenda items was how to regulate human genome editing in China in light of its <a href="https://theconversation.com/crispr-babies-raise-an-uncomfortable-reality-abiding-by-scientific-standards-doesnt-guarantee-ethical-research-108008">misuse in 2018</a>, when scientists modified the DNA of two human embryos before birth to have resistance against HIV infection. The controversy stems from the fact that because the technology is relatively early in its development, and its potential risks have not been reduced or eliminated, editing human embryos in ways they could pass on to their own offspring could lead to a variety of known and unknown adverse complications. The <a href="https://www.statnews.com/2023/03/06/genome-editing-summit-experts-worry-rule-changes-in-china-fall-short/">summit speakers noted</a> that while China has updated its guidelines and laws on human genome editing, it failed to address privately funded research – an issue other countries also face. Many countries, including the U.S., <a href="https://doi.org/10.1038/d41586-023-00625-w">do not have sufficiently robust regulatory frameworks</a> to prevent a repeat of the 2018 scandal.</p>
<p>We are a <a href="https://www.rit.edu/hudsonlab/">biochemist</a> and a <a href="https://www.rit.edu/directory/grssbi-gary-skuse">geneticist</a> who teach and conduct research in genomics and ethics at the Rochester Institute of Technology. As in our classrooms, debate about genome editing continues in the field.</p>
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<figcaption><span class="caption">Listening to different perspectives about CRISPR could lead to more balanced discussions about how to regulate it.</span></figcaption>
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<h2>What is genome editing?</h2>
<p>The <a href="https://theconversation.com/the-human-genome-project-pieced-together-only-92-of-the-dna-now-scientists-have-finally-filled-in-the-remaining-8-176138">human genome</a> typically consists of 23 pairs of chromosomes made of approximately 3.2 billion nucleotides – the building blocks of DNA. There are four nucleotides that make up DNA: adenine (A), thymine (T), guanine (G) and cytosine (C). If the genome were a book, each chromosome would be a chapter, each gene on a particular chromosome would be a paragraph and each paragraph would be made of individual letters (A, T, G or C). </p>
<p>One can imagine a book with over 3 billion characters might need editing to correct mistakes that occurred during the writing or copying processes. </p>
<p>Genome editing is a way for scientists to make specific changes to the DNA in a cell or in an entire organism by adding, removing or swapping in or out one or more nucleotides. In people, these changes can be done in somatic cells, those with DNA that cannot be inherited by offspring, or in gamete cells, those containing DNA that can be passed on to offspring. Genome editing of gamete cells, which includes egg or sperm, is controversial, as any changes would be passed on to descendants. Most <a href="https://doi.org/10.1089/crispr.2020.0082">existing guidelines and policies</a> prohibit its use at this time.</p>
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<figcaption><span class="caption">Geneticist Jennifer Doudna is one of the co-inventors of CRISPR/Cas9.</span></figcaption>
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<h2>How CRISPR works</h2>
<p>In 2012, scientists published a <a href="https://doi.org/10.1126/science.1225829">groundbreaking study</a> demonstrating how CRISPR, or Clustered Regularly Interspaced Short Palindromic Repeats, can be used to accurately change specific DNA sequences.</p>
<p>CRISPR’s natural origins are as a kind of immune response for bacteria. Bacteria that can be infected with viruses have evolved mechanisms to combat them. When a bacterium is infected with a particular virus, it keeps a small piece of the viral DNA sequence called a “spacer” in its own genome. This spacer is an exact match to the viral DNA. Upon subsequent infection, the bacterium is able to use the spacer to recruit a scissorlike protein called Cas9 that can sever new viral DNA attempting to integrate into the bacterium’s genome. This cut to the genetic material prevents the virus from replicating and killing its bacterial host.</p>
<p>After this discovery, scientists were able to fine-tune the system in the lab to be highly precise. They can sever DNA from a variety of cells, including human cells, at a specific location in the genome and subsequently edit it by adding, removing or swapping nucleotides. This is similar to adding or removing letters and words from a book. </p>
<p>This technology has the potential to treat diseases that have genetic origins. One of the summit’s sessions covered CRISPR’s ongoing experimental use to treat patients with <a href="https://doi.org/10.1056/NEJMoa2031054">sickle cell anemia and beta-thalassemia</a>, two blood disorders caused by mutations in the genes. Notably, genetic modification to treat sickle cell anemia and beta-thalassemia involves editing somatic cells, not germline cells. But as the summit speakers noted, whether these likely expensive therapies will be <a href="https://www.statnews.com/2023/03/07/crispr-sickle-cell-access/">accessible to the people who need them most</a>, especially in low- and middle-income countries, is a problem that requires changes to how treatments are sold.</p>
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<figcaption><span class="caption">Scientists have been testing ways to use CRISPR/Cas9 to treat sickle cell anemia.</span></figcaption>
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<h2>Ethics of human genome editing</h2>
<p><a href="https://doi.org/10.1016%2Fj.jmb.2018.05.044">Many questions remain</a> concerning the safety of genome editing, along with its potential to promote eugenics and exacerbate inequities and inequality.</p>
<p>A number of the summit’s sessions involved discussion on the ethics and regulation of the use of this tool. While the landmark 1979 <a href="https://www.hhs.gov/ohrp/regulations-and-policy/belmont-report/read-the-belmont-report/index.html">Belmont Report</a> outlined several ethical pillars to guide human research in the U.S., it was published before human genome editing was developed. In 2021, the World Health Organization <a href="https://www.who.int/news/item/12-07-2021-who-issues-new-recommendations-on-human-genome-editing-for-the-advancement-of-public-health">issued recommendations on human genome editing</a> as a tool to advance public health. There is <a href="https://doi.org/10.1146/annurev-genom-111320-091930">no current international law</a> governing human genome editing. </p>
<p>There is <a href="https://www.pewresearch.org/internet/2022/03/17/americans-are-closely-divided-over-editing-a-babys-genes-to-reduce-serious-health-risk/">still a debate</a> regarding how to use this technology. Some people equate genome editing to interfering with the work of God and argue that it shouldn’t be used at all, while others recognize its potential value and weigh that against its potential risks. The latter focuses on the fundamental question of <a href="https://www.scientificamerican.com/article/the-dark-side-of-crispr/">where to draw the line</a> between which applications are considered acceptable and which are not. For example, some people will agree that using genome editing to modify a defective gene that may lead to an infant’s death if untreated is acceptable. But these same people may frown upon the use of genome editing to ensure that an unborn child has specific physical features such as blue eyes or blond hair.</p>
<p>Nor is there consensus about <a href="https://doi.org/10.1001/jama.2022.13468">what diseases</a> are desirable targets. For example, it may be acceptable to modify a gene to prevent an infant’s death but not acceptable to modify one that prevents a disease later in life, such as the gene responsible for <a href="https://www.mayoclinic.org/diseases-conditions/huntingtons-disease/symptoms-causes/syc-20356117">Huntington’s disease</a>.</p>
<p>The potential for positive applications of human genome editing is both numerous and tantalizing. But establishing informed regulatory legislation everyone can agree on is and will continue to be a challenge. Conferences such as the human genome editing summit are one way to continue important discussions and educate the scientific community and the public on the benefits and risks of genome editing.</p><img src="https://counter.theconversation.com/content/200983/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andre Hudson receives funding from the National Institutes of Health</span></em></p><p class="fine-print"><em><span>Gary Skuse has received funding from the National Science Foundation. </span></em></p>Following the controversial births of the first gene-edited babies, a major focus of the Third International Summit on Human Genome Editing was responsible use of CRISPR.André O. Hudson, Interim Dean/Professor-College of Science, Rochester Institute of TechnologyGary Skuse, Professor of Bioinformatics, Rochester Institute of TechnologyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1967142022-12-20T17:52:36Z2022-12-20T17:52:36ZDid He Jiankui ‘Make People Better’? Documentary spurs a new look at the case of the first gene-edited babies<figure><img src="https://images.theconversation.com/files/501995/original/file-20221219-14-6lxobo.jpg?ixlib=rb-1.1.0&rect=218%2C11%2C2914%2C2144&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">He Jiankui seemed unprepared for the furor set off by his bombshell announcement.</span> <span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:He_Jiankui.jpg">The He Lab/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>In the four years since an experiment by disgraced scientist He Jiankui resulted in the <a href="https://apnews.com/article/ap-top-news-international-news-ca-state-wire-genetic-frontiers-health-4997bb7aa36c45449b488e19ac83e86d">birth of the first babies with edited genes</a>, numerous articles, books and <a href="https://nap.nationalacademies.org/catalog/25665/heritable-human-genome-editing">international</a> <a href="https://www.who.int/groups/expert-advisory-committee-on-developing-global-standards-for-governance-and-oversight-of-human-genome-editing">commissions</a> have reflected on whether and how heritable genome editing – that is, modifying genes that will be passed on to the next generation – should proceed. They’ve reinforced an international consensus that it’s premature to proceed with heritable genome editing. Yet, concern remains that some individuals might buck that consensus and recklessly forge ahead – just as He Jiankui did.</p>
<p>Some observers – <a href="https://scholar.google.com/citations?user=yebS-LIAAAAJ&hl=en&oi=ao">myself included</a> – have <a href="https://theconversation.com/rogue-science-strikes-again-the-case-of-the-first-gene-edited-babies-107684">characterized He as a rogue</a>. However, the new documentary “<a href="https://makepeoplebetterfilm.com/">Make People Better</a>,” directed by filmmaker Cody Sheehy, leans toward a different narrative. In its telling, He was a misguided centerpiece of a broader ecosystem that subtly and implicitly supported rapid advancement in gene editing and reproductive technologies. That same system threw He under the bus – <a href="https://www.technologyreview.com/2019/12/30/131061/he-jiankui-sentenced-to-three-years-in-prison-for-crispr-babies/">and into prison</a> – when it became evident that the global community strongly rejected his experiments.</p>
<h2>Creation of the ‘CRISPR babies’</h2>
<p>“Make People Better” outlines an already well-documented saga, tracing the path of He from a promising young scientist at Rice and Stanford to a driven researcher establishing a laboratory in China that secretly worked to make heritable genome editing a reality.</p>
<p>He’s experiment involved using the <a href="https://theconversation.com/nobel-prize-for-crispr-honors-two-great-scientists-and-leaves-out-many-others-147730">CRISPR-Cas9 technique</a>. Sometimes compared to “molecular scissors,” this precision tool allows scientists to make very specific edits to DNA in living cells. He used CRISPR to alter the CCR5 gene in human embryos with the goal of conferring immunity to HIV. These embryos were brought to term, resulting in the birth of at <a href="https://www.newscientist.com/article/mg25533930-700-whats-next-for-the-gene-edited-children-from-crispr-trial-in-china/">least three children with altered DNA</a>. </p>
<p>The revelation of the births of the first gene-edited babies in November 2018 resulted in an international uproar. A <a href="https://www.theatlantic.com/science/archive/2018/12/15-worrying-things-about-crispr-babies-scandal/577234/">laundry list</a> of ethical failings in He’s experiment <a href="https://www.nature.com/articles/d41586-018-07573-w">quickly became evident</a>. There was insufficient proof that editing embryos with CRISPR was safe enough to be done in humans. Appropriate regulatory approval had <a href="https://www.scmp.com/news/china/science/article/2182964/china-confirms-gene-edited-babies-blames-scientist-he-jiankui">not been obtained</a>. The parents’ consent was <a href="https://link.springer.com/article/10.1007/s11673-019-09953-x">grossly inadequate</a>. And the whole endeavor was <a href="https://apnews.com/article/health-science-china-medical-ethics-ap-top-news-13303d99c4f849829e98350301e334a9">shrouded in secrecy</a>.</p>
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<figcaption><span class="caption">Trailer for the documentary ‘Make People Better.’</span></figcaption>
</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>
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<p>An uncomfortable tension lies at the center of “Make People Better.” </p>
<p>On the one hand, the documentary gives substantial attention to Hurlbut and Ryan, who emphasize that He did not act alone. He discussed his plans with <a href="https://doi.org/10.1126/science.365.6452.430">dozens of people</a> in China and around the world, whose implicit support was essential to both the experiment and his confidence that he was doing nothing wrong.</p>
<p>On the other hand, the documentary focuses on understanding He’s background, motives and ultimate fate. Other figures who might have influenced He to take a different path fade into the background – sometimes quite literally, appearing for only seconds before the documentary moves on.</p>
<p>Indeed, as a biomedical ethicist, I believe there is good reason to put responsibility for the debacle squarely on He’s shoulders. Before the news broke in 2018, international panels of experts had already issued <a href="https://www.nationalacademies.org/news/2015/12/on-human-gene-editing-international-summit-statement">advisory statements</a> that heritable gene editing was premature. Individuals like Hurlbut personally advised He as much. The secrecy of the experiment itself is a testament: He must have suspected the international community would reject the experiment if they knew what was going on. </p>
<p>If He had gone through proper, transparent channels – <a href="https://www.cos.io/initiatives/prereg">preregistering the trial</a> and consulting publicly with international experts on his plans before he began – the whole saga could have been averted. He chose a different, more dangerous and secretive path from the vast majority of researchers working in reproductive biotechnology, which I suggest must be acknowledged.</p>
<p>The documentary does not reflect critically on its own title. The origin of the phrase “make people better” is surprising and the film’s most clever narrative moment, so I won’t spoil it. But does heritable gene editing really make people better? <a href="https://doi.org/10.1111/bioe.12878">Perhaps instead</a>, it makes better people. </p>
<p>The gene-edited babies were created via in vitro fertilization specifically as a part of He’s experiment. They would not have existed if He had never gotten involved in gene editing. So, some would argue, He did not save any individual from contracting HIV. Rather, he created new people potentially less likely to contract HIV than the general population. </p>
<p><a href="https://doi.org/10.1007/s11019-020-09947-2">I contend</a> that this doesn’t mean gene editing is pointless. From a population health perspective, gene editing could save lives by reducing the incidence of certain diseases. But this perspective does change the moral tenor of gene editing, perhaps reducing its urgency.</p>
<p>What’s more, editing CCR5 is a dubious means to improve human well-being, since there are already effective ways to prevent HIV infection that are far less risky and uncertain than heritable gene editing. <a href="https://doi.org/10.17226/25665">Scientific consensus suggests</a> that the best first-in-human candidates for heritable gene editing are instead devastating genetic disorders that cannot be ameliorated in other ways.</p>
<h2>The future for He Jiankui</h2>
<p>Perhaps due to the timing of its filming, the documentary does not dwell on He being <a href="https://www.science.org/content/article/chinese-scientist-who-produced-genetically-altered-babies-sentenced-3-years-jail">sentenced to three years in Chinese prison</a> as a result of the experiment, nor mention that <a href="https://www.technologyreview.com/2022/04/04/1048829/he-jiankui-prison-free-crispr-babies/">he was released</a> early in 2022.</p>
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<p>Evidently, He is not content to fade quietly into obscurity. He says he is slated in March 2023 to <a href="https://pandaily.com/chinese-gene-editing-scientist-he-jiankui-sets-up-beijing-lab-following-prison-release/">give a talk at the University of Oxford</a> that may shed more light on his motives and actions. In the meantime, he has <a href="https://www.statnews.com/2022/11/29/after-prison-crispr-babies-scientist-is-attempting-comeback/">established a new biotech start-up</a> focused on developing gene therapies. To be clear, this work does not involve editing embryos.</p>
<p>Still, it appears prison has not diminished He’s ambition. <a href="https://www.scmp.com/news/china/science/article/3201896/chinese-scientist-behind-gene-edited-babies-speak-oxford-university">He claims</a> that he could develop a cure for the degenerative genetic disease Duchenne muscular dystrophy – if he receives funding in excess of US$100 million. </p>
<p>To me, this ambition reflects a curious symmetry between Regalado and He in “Make People Better.” Both are driven to be first, to be at the forefront of their respective fields. Sometimes, as with Regalado, this initiative can be good – his intrepid reporting and instinct to publish quickly brought He’s unethical experiment to a rapid close. But in other cases, like He’s, that drive can lead to dangerous science that runs roughshod over ethics and good governance. </p>
<p>Perhaps, then, the best lesson a viewer can take from “Make People Better” is that ambition is a double-edged sword. In the years to come, it will be up to the international community to keep such ambition in check and ensure proper restrictions and oversight on heritable genome editing.</p><img src="https://counter.theconversation.com/content/196714/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>G. Owen Schaefer does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Scientific and public uproar resulted when the Chinese scientist announced the births of the first human babies with heritable edits to their genes. A new documentary reexamines the saga.G. Owen Schaefer, Assistant Professor in Biomedical Ethics, National University of SingaporeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1867972022-07-14T18:35:13Z2022-07-14T18:35:13ZY chromosome loss through aging can lead to an increased risk of heart failure and death from cardiovascular disease, new research finds<figure><img src="https://images.theconversation.com/files/474141/original/file-20220714-32290-2fajn7.jpg?ixlib=rb-1.1.0&rect=3%2C9%2C2106%2C1404&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Chromosomes change over time, whether through the process of aging or exposure to harmful substances in the environment.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/and-y-chromosomes-royalty-free-image/88179880">Steven Puetzer/The Image Bank</a></span></figcaption></figure><p><em>The <a href="https://theconversation.com/us/topics/research-brief-83231">Research Brief</a> is a short take about interesting academic work.</em></p>
<h2>The big idea</h2>
<p>The Y chromosome can be lost through the process of aging, and this can lead to an increased risk of heart failure and cardiovascular disease, according to a 2022 study my colleagues <a href="https://scholar.google.com/citations?user=hM9Ve60AAAAJ&hl=en">and I</a> published in the journal <a href="https://science.org/doi/10.1126/science.abn3100">Science</a>.</p>
<p>While most women have two X chromosomes, most men have one X and one Y. And many people with Y chromosomes start to lose them in a fraction of the cells in their body as they age.</p>
<p>While loss of the Y chromosome was <a href="https://doi.org/10.1038/1971080a0">first observed in 1963</a>, it was not <a href="https://doi.org/10.1038/ng.2966">until 2014</a> that researchers found an association between loss of the Y chromosome and shorter life span. Y chromosome loss has since been linked to a number of <a href="https://doi.org/10.1038/ng.2966">age-related diseases</a>, such as cancer and Alzheimer’s disease. However, it has been unknown whether this loss is just another benign indicator of aging, like gray hair or skin wrinkles, or whether it has a direct role in promoting disease.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/of7vrIIcTa0?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Over time, the degrading Y chromosome may play an increasingly smaller role in development.</span></figcaption>
</figure>
<p>My colleagues and I wanted to figure out if Y chromosome loss directly causes disease and, if so, how. Historically, the Y chromosome has been difficult to study because much of its genetic material is repetitive – it’s easy to get “lost” trying to decipher the sequence.</p>
<p>However, we were able to take advantage of these repeat sequences by targeting them with the DNA-editing tool <a href="https://medlineplus.gov/genetics/understanding/genomicresearch/genomeediting/">CRISPR</a>. We used CRISPR to introduce breaks into the Y chromosome DNA of white blood cells in mice, destroying and eliminating the Y chromosome. We chose white blood cells in particular because they tend to have a <a href="https://doi.org/10.1038/s41598-020-59963-8">high prevalence</a> of Y chromosome loss.</p>
<p>We found that while loss of the Y chromosome did not have immediate effects on the young mice, they ended up aging poorly, dying at an earlier age than mice that still had Y chromosomes. They also had more buildup of scar tissue in the heart, a condition called <a href="https://doi.org/10.1038%2Fnri1412">fibrosis</a>, as well as a stronger decline in heart function after induced heart failure. Treating the mice with a drug that blocks heart scarring, however, was able to restore lost heart function. </p>
<p>We then evaluated the effects of Y chromosome loss in people. We analyzed data from the <a href="https://www.ukbiobank.ac.uk">U.K. Biobank</a>, a large database of medical and genetic data from 500,000 participants in the U.K. We found that men who had lost their Y chromosomes in over 40% of their white blood cells had a 31% increased risk of dying from cardiovascular disease compared with men who hadn’t lost their Y chromosomes, including a two- to threefold increased risk of dying from congestive heart failure or heart disease. In other words, those with the greatest Y chromosome loss had the greatest risk of death from cardiovascular disease.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/474167/original/file-20220714-32349-yfkrfr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Human karyotype missing a Y chromosome" src="https://images.theconversation.com/files/474167/original/file-20220714-32349-yfkrfr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/474167/original/file-20220714-32349-yfkrfr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=491&fit=crop&dpr=1 600w, https://images.theconversation.com/files/474167/original/file-20220714-32349-yfkrfr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=491&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/474167/original/file-20220714-32349-yfkrfr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=491&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/474167/original/file-20220714-32349-yfkrfr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=617&fit=crop&dpr=1 754w, https://images.theconversation.com/files/474167/original/file-20220714-32349-yfkrfr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=617&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/474167/original/file-20220714-32349-yfkrfr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=617&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Screening for Y chromosome loss could help lead to earlier treatments for age-related conditions.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/digitally-generated-image-of-karyotype-over-white-royalty-free-image/649121991">Olympia Valla/EyeEm via Getty Images</a></span>
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</figure>
<h2>Why it matters</h2>
<p>Men are reported to have shorter life spans than women in many countries. In industrialized countries like the U.S., this is typically a <a href="https://www.census.gov/library/publications/2020/demo/p25-1145.html">difference of five years</a>. While <a href="https://time.com/5538099/why-do-women-live-longer-than-men/">social, behavioral and other genetic factors</a> may also be at play, they don’t entirely account for the differences in life span.</p>
<p>Our work shows that loss of the Y chromosome can directly contribute to age-related diseases like heart disease through tissue scarring. We believe that a better understanding of how the Y chromosome may contribute to age-related diseases, and potentially the process of aging itself, could lead to ways to screen and prevent excessive tissue scarring that can lead to cardiovascular disease.</p>
<h2>What still isn’t known</h2>
<p>While our study primarily focused on the heart, we also found that mice with Y chromosome loss also had scarring in their kidneys and lungs as well as accelerated cognitive impairment as they aged. Further research can help clarify the role of Y chromosome loss in diseases affecting other parts of the body.</p>
<h2>What’s next</h2>
<p>We are currently searching for specific genes that are lost with the Y chromosome that may be responsible for the disease-causing effects of Y chromosome loss. This information can help us better analyze exactly how loss of the Y chromosome can lead to disease and aid in the development of treatments for it.</p><img src="https://counter.theconversation.com/content/186797/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kenneth Walsh receives funding from the National Institutes of Health and the National Aeronautics and Space Administration. </span></em></p>The negative health effects of Y chromosome loss could be one potential reason women tend to live longer than men.Kenneth Walsh, Professor of Internal Medicine, University of VirginiaLicensed 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>
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<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>
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<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>
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</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>
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<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/1752902022-02-27T13:08:39Z2022-02-27T13:08:39ZOrgan transplants from pigs: Medical miracle or pandemic in the making?<figure><img src="https://images.theconversation.com/files/447227/original/file-20220218-3064-xtzvrp.jpg?ixlib=rb-1.1.0&rect=422%2C35%2C4922%2C3332&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Xenotransplantation is the transplanting of cells, tissues or organs from animals to humans. Pre-clinical trials of organ transplant from pigs have addressed some of the technical barriers.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>Three out of four <a href="https://www.cdc.gov/onehealth/basics/zoonotic-diseases.html">new diseases are zoonotic</a>, meaning they have evolved to infect new host species. For example, a mutated <a href="https://www.cdc.gov/flu/avianflu/virus-transmission.htm">bird-flu virus</a> may jump from wild birds to free-range domestic poultry and then to humans who are in contact with poultry. Similar pathways have led to infection by the pathogens that cause <a href="https://doi.org/10.1038/nrmicro.2017.45">Ebola, Zika, HIV, Lyme disease and likely COVID-19</a>.</p>
<p>If a new medical technology increased the risk of a new zoonotic pandemic — however marginally — how would society decide the balance of risk and benefit? If you needed new lungs that were only available in another country, would a health prohibition on the transplant in your own country stop you? </p>
<p>New developments in organ transplant technology may have streamlined a pathway for new zoonotic diseases, but the biotechnology innovators and medical research institutes have not engaged the public on the risks. Failing to do so may jeopardize the potential of a promising therapy.</p>
<h2>Xenotransplantation</h2>
<p>Over 4,400 Canadians are waitlisted for the lifesaving transplant of a new kidney, liver or lung. In 2019, <a href="https://www.blood.ca/en/stories/data-offers-hope-patients-waiting-organ-transplant">250 died waiting</a>. In the United States and elsewhere, <a href="https://www.organdonor.gov/learn/organ-donation-statistics">the supply gap is more extreme</a> and high hopes ride on xenotransplantation: the transplanting of cells, tissues or organs from animals. </p>
<p>Pre-clinical trials of organ transplants from pigs have addressed the technical barriers to xenotransplantation, reducing the likelihood of rejection. Last summer, Maryland School of Medicine surgeons reported the 31-day survival of a baboon after receiving a <a href="https://doi.org/10.1111/ajt.16809">lung from a genetically modified pig</a>. </p>
<p>Weeks later, a team at New York University transplanted a kidney from a genetically modified pig into a <a href="https://doi.org/10.1111/xen.12718">brain-dead person</a>. In December 2021, surgeons at Maryland School of Medicine transplanted a genetically modified pig heart into a <a href="https://doi.org/10.1038/d41586-022-00111-9">living 57-year-old man</a>. </p>
<p>All projects were approved under U.S. Food and Drug Administration (FDA) regulations, and corporate funding was supplemented by the U.S. National Institutes of Health. The next step with the FDA is to approve clinical trials. Normalization of xenotransplantation could happen before there is informed public acceptance of the benefits and risks.</p>
<h2>A potential zoonotic pathway</h2>
<p>As a developmental geneticist, it has been exciting to track these advances. The revolution in designer gene editing (known as CRISPR-Cas9) makes this stunning progress possible. <a href="https://doi.org/10.1126/science.aan4187">CRISPR allows molecules on the surface of pig cells to be modified</a> so the human immune system will not trigger tissue rejection.</p>
<figure class="align-center ">
<img alt="Illustration in blue tones of a human torso with respiratory tract and lungs in red" src="https://images.theconversation.com/files/447231/original/file-20220218-13070-hep7im.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/447231/original/file-20220218-13070-hep7im.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=465&fit=crop&dpr=1 600w, https://images.theconversation.com/files/447231/original/file-20220218-13070-hep7im.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=465&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/447231/original/file-20220218-13070-hep7im.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=465&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/447231/original/file-20220218-13070-hep7im.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=585&fit=crop&dpr=1 754w, https://images.theconversation.com/files/447231/original/file-20220218-13070-hep7im.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=585&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/447231/original/file-20220218-13070-hep7im.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=585&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Zoonotic bacteria and viruses enter most readily through the delicate surfaces of the respiratory tract.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>To prevent human transplant recipients from being infected with pig <a href="https://www.genome.gov/genetics-glossary/Retrovirus">retroviruses</a> (viruses that can integrate their genetic material into the host’s cells), the retroviruses hiding in the pig genome have been <a href="https://doi.org/10.1111/xen.12595">removed by CRISPR editing</a>. The risk of transferring a disease directly from a genetically modified donor pig to the human host is negligible.</p>
<p>However, disease-free transplanted pig organs could become infected after transplantation. Zoonotic bacteria and viruses enter hosts most readily through the <a href="https://doi.org/10.1051/vetres:2006062">delicate surfaces of the respiratory tract</a>, as with COVID-19. Living pig cells in a transplanted lung could readily be infected by an inhaled pig virus, including a novel virus from a wild animal host that has evolved to infect pigs. </p>
<p>After entering the human body, a replicating zoonotic virus could generate millions of mutations a day, because their mechanism for gene copying <a href="https://doi.org/10.3390/v13091882">is naturally error prone</a>. A pig virus replicating in a lung transplanted into a human could <a href="https://theconversation.com/how-do-viruses-mutate-and-jump-species-and-why-are-spillovers-becoming-more-common-134656">produce variants</a> that may be capable of recognizing and infecting human cells. Although likely a rare event, it is not impossible that this could trigger a new zoonotic pandemic.</p>
<h2>Risk, fear and polarization</h2>
<p>The scenario described above could evoke risk and fear from a complex new medical technology. It parallels the thinking involved in <a href="https://doi.org/10.1038/s41591-021-01459-7">vaccine hesitancy</a> or the <a href="https://www.scientificamerican.com/article/why-people-oppose-gmos-even-though-science-says-they-are-safe/">distrust of genetically modified foods</a>. Both are well anchored in today’s political culture. In both cases, citizens increasingly demand prior consent and the choice to opt out — despite possible risks to public health. <a href="https://doi.org/10.1038/s41598-022-05498-z">Vaccine hesitancy</a> has increased the death toll from COVID-19 and delayed economic recovery from the pandemic.</p>
<p>In contrast, distrust of the industrialization of food has discouraged introduction of genetically modified foods that <a href="https://doi.org/10.4161/21645698.2014.967570">enhance nutrition or sustain agricultural productivity</a> in a warming climate. Consumers question whether genetically modified organisms (GMOs) exist for public benefit or for corporate profit.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/447229/original/file-20220218-19-vy6cvf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A protester wearing a winter hat with their face covered with a scarf, hold a paper plate that says 'No GMOs on my plate'" src="https://images.theconversation.com/files/447229/original/file-20220218-19-vy6cvf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/447229/original/file-20220218-19-vy6cvf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=798&fit=crop&dpr=1 600w, https://images.theconversation.com/files/447229/original/file-20220218-19-vy6cvf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=798&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/447229/original/file-20220218-19-vy6cvf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=798&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/447229/original/file-20220218-19-vy6cvf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1003&fit=crop&dpr=1 754w, https://images.theconversation.com/files/447229/original/file-20220218-19-vy6cvf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1003&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/447229/original/file-20220218-19-vy6cvf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1003&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Distrust of the industrialization of food has discouraged introduction of GMO foods.</span>
<span class="attribution"><span class="source">(CP PHOTO/Paul Chiasson)</span></span>
</figcaption>
</figure>
<p>Increasingly, health issues such as <a href="https://theconversation.com/politicizing-covid-19-vaccination-efforts-has-fuelled-vaccine-hesitancy-175416">vaccination</a>, vaping or genetic testing generate highly polarized <a href="https://doi.org/10.1093/ntr/ntaa276">platforms for misinformation</a>, debate and political leverage. <a href="https://thedecisionlab.com/insights/society/social-media-and-moral-outrage/">Social media algorithms amplify extreme positions and elicit strong emotional reactions</a> at the <a href="http://dx.doi.org/10.1177/1461444818822813">expense of the middle ground</a>. When communications from the scientific community are reactive, poorly targeted or <a href="https://doi.org/10.1080/02691728.2020.1739778">unintelligible to the average person</a>, the influence of science in the policy process is diminished.</p>
<p>In 2022, progress in xenotransplant technology makes <a href="https://edition.cnn.com/2022/01/15/opinions/pig-heart-transplant-big-deal-reiner/index.html">good news stories</a>. Immense pressure to resolve the growing organ shortage for transplantation may tempt the biotechnology business and public regulators to be insufficiently critical as they seek permission to proceed with clinical studies. They must prepare for the nature and scale of backlash from those tired of experts and mistrustful of corporate motivation and institutional authority. </p>
<p>Concern about zoonosis from transplants was <a href="https://www.nuffieldbioethics.org/publications/xenotransplantation">voiced over twenty years ago</a>, long before CRISPR transformed the field. <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents/phs-guideline-infectious-disease-issues-xenotransplantation">Since then</a>, there appear to be no hard facts or even a call for research on zoonotic infection through xenotransplants after transplantation. Bioethicists are <a href="https://www.thehastingscenter.org/xenotransplantation-three-areas-of-concern/">flagging the issue now</a>, but the silence about xenotransplant zoonosis from biotechnology corporations and their affiliated preclinical research institutes leaves an open door to a narrative motivated by skepticism and distrust. It is incumbent on them to lead a public dialogue on managing the risk of novel zoonotic diseases arising from infection after transplantation.</p><img src="https://counter.theconversation.com/content/175290/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>J Roger Jacobs receives funding from the Natural Sciences and Engineering Research Council of Canada.</span></em></p>New developments in organ transplants from animals show promise. However, there has been no public engagement about a potential risk. It may streamline a pathway to humans for new zoonotic diseases.J Roger Jacobs, Professor, Department of Biology, McMaster 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>
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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>
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<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>
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<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>
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<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/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>
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Read more:
<a href="https://theconversation.com/what-is-crispr-the-gene-editing-technology-that-won-the-chemistry-nobel-prize-147695">What is CRISPR, the gene editing technology that won the Chemistry Nobel prize?</a>
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<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">
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<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>
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<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>
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<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>
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<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>
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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>
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<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">
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<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>
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<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>
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<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">
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<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>
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<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>
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</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/1578432021-04-22T12:25:43Z2021-04-22T12:25:43ZLab-grown embryos and human-monkey hybrids: Medical marvels or ethical missteps?<figure><img src="https://images.theconversation.com/files/396376/original/file-20210421-23-1cklx15.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1198%2C808&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Researchers have grown mammal embryos later into development than ever before in an artificial womb.</span> <span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Geometric_Progression.jpg#/media/File:Geometric_Progression.jpg">Vitalii Kyryk/WikimediaCommons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>In Aldous Huxley’s 1932 novel “<a href="https://www.oxfordreference.com/view/10.1093/oi/authority.20110803095525181">Brave New World</a>,” people aren’t born from a mother’s womb. Instead, embryos are grown in artificial wombs until they are brought into the world, a process called ectogenesis. In the novel, technicians in charge of the hatcheries manipulate the nutrients they give the fetuses to make the newborns fit the desires of society. Two recent scientific developments suggest that Huxley’s imagined world of functionally manufactured people is no longer far-fetched.</p>
<p>On March 17, 2021, an Israeli team announced that it had grown mouse embryos for 11 days – about half of the gestation period – in <a href="https://doi.org/10.1038/s41586-021-03416-3">artificial wombs</a> that were essentially bottles. Until this experiment, no one had grown a mammal embryo outside a womb this far into pregnancy. Then, on April 15, 2021, a U.S. and Chinese team announced that it had successfully grown, for the first time, <a href="https://doi.org/10.1016/j.cell.2021.03.020">embryos that included both human and monkey cells</a> in plates to a stage where organs began to form. </p>
<p>As both a <a href="https://scholar.google.com/citations?hl=en&user=wQsQxFoAAAAJ">philosopher and a biologist</a> I cannot help but ask how far researchers should take this work. While creating chimeras – the name for creatures that are a mix of organisms – might seem like the more ethically fraught of these two advances, ethicists think the medical benefits far outweigh the ethical risks. However, ectogenesis could have far-reaching impacts on individuals and society, and the prospect of babies grown in a lab has not been put under nearly the same scrutiny as chimeras.</p>
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<figcaption><span class="caption">Mouse embryos were grown in an artificial womb for 11 days, and organs had begun to develop.</span></figcaption>
</figure>
<h2>Growing in an artificial womb</h2>
<p>When in vitro fertilization first emerged in the late 1970s, the press called IVF embryos “test-tube babies,” though they are nothing of the sort. These embryos are implanted into the uterus within a day or two after doctors fertilize an egg in a petri dish.</p>
<p>Before the Israeli experiment, researchers had not been able to grow mouse embryos outside the womb for more than four days – providing the embryos with enough oxygen had been too hard. The team spent <a href="https://doi.org/10.1126/science.abi5734">seven years</a> creating a system of slowly spinning glass bottles and controlled atmospheric pressure that simulates the placenta and provides oxygen.</p>
<p>This development is a major step toward ectogenesis, and scientists expect that it will be possible to extend mouse development further, possibly <a href="https://www.technologyreview.com/2021/03/17/1020969/mouse-embryo-grown-in-a-jar-humans-next/">to full term outside the womb</a>. This will likely require new techniques, but at this point it is a problem of scale – being able to accommodate a larger fetus. This appears to be a <a href="http://hdl.handle.net/10822/547926">simpler challenge to overcome</a> than figuring out something totally new like supporting organ formation.</p>
<p>The Israeli team plans to <a href="https://www.technologyreview.com/2021/03/17/1020969/mouse-embryo-grown-in-a-jar-humans-next/">deploy its techniques on human embryos</a>. Since mice and humans have similar developmental processes, it is likely that the team will succeed in growing human embryos in artificial wombs. </p>
<p>To do so, though, members of the team need permission from their ethics board. </p>
<p>CRISPR – a technology that can cut and paste genes – already allows scientists to manipulate an embryo’s genes after fertilization. Once fetuses can be grown outside the womb, as in Huxley’s world, researchers will also be able to modify their growing environments to further influence what <a href="https://doi.org/10.1093/jn/134.9.2169">physical and behavioral qualities these parentless babies exhibit</a>. Science still has a way to go before fetus development and births outside of a uterus become a reality, but researchers are getting closer. The question now is how far humanity should go down this path.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/396377/original/file-20210421-21-17un52t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A drawing of a half–eagle, half–horse griffin." src="https://images.theconversation.com/files/396377/original/file-20210421-21-17un52t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/396377/original/file-20210421-21-17un52t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=634&fit=crop&dpr=1 600w, https://images.theconversation.com/files/396377/original/file-20210421-21-17un52t.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=634&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/396377/original/file-20210421-21-17un52t.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=634&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/396377/original/file-20210421-21-17un52t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=797&fit=crop&dpr=1 754w, https://images.theconversation.com/files/396377/original/file-20210421-21-17un52t.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=797&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/396377/original/file-20210421-21-17un52t.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=797&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Chimeras evoke images of mythological creatures of multiple species – like this 15th-century drawing of a griffin – but the medical reality is much more sober.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Martin_Schongauer,_The_griffin_(15th_century).jpg#/media/File:Martin_Schongauer,_The_griffin_(15th_century).jpg">Martin Schongauer/WikimediaCommons</a></span>
</figcaption>
</figure>
<h2>Human-monkey hybrids</h2>
<p>Human–monkey hybrids might seem to be a much scarier prospect than babies born from artificial wombs. But in fact, the recent research is more a step toward an important medical development than an ethical minefield.</p>
<p>If scientists can grow human cells in monkeys or other animals, it should be possible to <a href="https://doi.org/10.1016/j.cell.2021.03.044">grow human organs</a> too. This would solve the problem of <a href="https://www.bbc.com/news/science-environment-56767517">organ shortages</a> around the world for people needing transplants.</p>
<p>But keeping human cells alive in the embryos of other animals for any length of time has proved to be extremely difficult. In the <a href="https://doi.org/10.1016/j.cell.2021.03.020">human-monkey chimera experiment</a>, <a href="https://www.bbc.com/news/science-environment-56767517">a team of researchers implanted</a> 25 human stem cells into embryos of crab-eating macaques – a type of monkey. The researchers then <a href="https://doi.org/10.1016/j.cell.2021.03.044">grew these embryos</a> for 20 days in petri dishes.</p>
<p>After 15 days, the human stem cells had disappeared from most of the embryos. But at the end of the 20-day experiment, three embryos still contained human cells that had grown as part of the region of the embryo where they were embedded. For scientists, the challenge now is to figure out how to maintain human cells in chimeric embryos for longer.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/396400/original/file-20210421-17-162zdc2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A drawing of test tubes with embryos inside." src="https://images.theconversation.com/files/396400/original/file-20210421-17-162zdc2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/396400/original/file-20210421-17-162zdc2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/396400/original/file-20210421-17-162zdc2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/396400/original/file-20210421-17-162zdc2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/396400/original/file-20210421-17-162zdc2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/396400/original/file-20210421-17-162zdc2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/396400/original/file-20210421-17-162zdc2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The ability to grow true test–tube babies raises many ethical questions.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/conceptual-image-of-human-cloning-royalty-free-image/1287023975?adppopup=true">Carol Yepes/Moment via Getty Images</a></span>
</figcaption>
</figure>
<h2>Regulating these technologies</h2>
<p>Some ethicists have begun to worry that researchers are <a href="https://doi.org/10.1016/j.cell.2021.03.044">rushing into a future</a> of chimeras without adequate preparation. Their main concern is the <a href="https://www.bbc.com/news/science-environment-56767517">ethical status of chimeras</a> that contain human and nonhuman cells – especially if the human cells integrate into sensitive regions <a href="https://doi.org/10.1016/j.cell.2021.03.044">such as a monkey’s brain</a>. What rights would such creatures have?</p>
<p>However, there seems to be an emerging consensus that the potential medical benefits justify a step-by-step extension of this research. Many ethicists are urging <a href="https://doi.org/10.1016/j.cell.2021.03.044">public discussion</a> of appropriate regulation to determine how close to viability these embryos should be grown. One proposed solution is to limit growth of these embryos to the first trimester of pregnancy. Given that researchers don’t plan to grow these embryos beyond the stage when they can <a href="https://doi.org/10.1016/j.cell.2021.03.044">harvest rudimentary organs</a>, I don’t believe chimeras are ethically problematic compared with the true test–tube babies of Huxley’s world.</p>
<p>Few ethicists have broached the problems posed by the ability to use ectogenesis to engineer human beings to fit societal desires. Researchers have yet to conduct experiments on human ectogenesis, and for now, scientists lack the techniques to bring the embryos to full term. However, without regulation, I believe researchers are likely to try these techniques on human embryos – just as the now-infamous He Jiankui <a href="https://thehill.com/opinion/healthcare/422891-how-we-proceed-with-human-gene-editing-will-be-the-debate-of-the-future">used CRISPR to edit human babies</a> without properly assessing safety and desirability. Technologically, it is a matter of time before mammal embryos can be brought to term outside the body. </p>
<p>[<em>Over 100,000 readers rely on The Conversation’s newsletter to understand the world.</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=100Ksignup">Sign up today</a>.]</p>
<p>While people may be uncomfortable with ectogenesis today, this discomfort could pass into familiarity as happened with IVF. But scientists and regulators would do well to reflect on the wisdom of permitting a process that could allow someone to engineer human beings without parents. As <a href="https://doi.org/10.1002/j.1552-146x.2011.tb00098.x">critics have warned</a> in the context of CRISPR-based genetic enhancement, pressure to change future generations to meet societal desires will be unavoidable and dangerous, regardless of whether that pressure comes from an authoritative state or cultural expectations. In Huxley’s imagination, hatcheries run by the state grew a large numbers of identical individuals as needed. That would be a very different world from today.</p><img src="https://counter.theconversation.com/content/157843/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sahotra Sarkar does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Researchers have grown the first human-monkey hybrid embryos as well as mouse embryos in artificial wombs late into development. These biomedical breakthroughs raise different ethical quandaries.Sahotra Sarkar, Professor of Philosophy and Integrative Biology, The University of Texas at AustinLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1581902021-04-09T09:19:45Z2021-04-09T09:19:45ZThree ways RNA is being used in the next generation of medical treatment<figure><img src="https://images.theconversation.com/files/393984/original/file-20210408-23-i5z0c8.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C7668%2C4320&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">RNA carries copies of genetic information from DNA.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/coronavirus-rna-strand-medical-illustration-3d-1699960924">CROCOTHERY/ Shutterstock</a></span></figcaption></figure><p>You might have heard the term “RNA” recently thanks to the development of the <a href="https://theconversation.com/how-do-mrna-vaccines-work-and-why-do-you-need-a-second-dose-5-essential-reads-157198">Pfizer and Moderna mRNA vaccines</a>, which protect against COVID-19. But the potential medical uses of RNA molecules go much further than vaccines.</p>
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<p>RNAs, or ribonucleic acids, are some of the most important molecules for life on this planet. RNA is found in every cell in the body, and plays an important role in the flow of genetic information. </p>
<p>“Messenger” RNAs (mRNAs) copy and carry the genetic instructions from our DNA to the protein-making factories of our cells (ribosomes), which can then create the biological components and machinery they need to work. For example, actin proteins give cells their shape and structure and are crucial to muscle contraction.</p>
<p>RNA also help other biomolecules find each other, and help bring other proteins and RNAs together. These functions are crucial in managing the many levels of gene regulation, which is itself important for proper functioning of the body.</p>
<p>RNA’s wide range of capabilities, as well as having a simple molecular sequence that can easily be read by researchers, has made it an extremely useful tool in the development of recent biomedical technologies – including <a href="https://pubmed.ncbi.nlm.nih.gov/22745249/">CRISPR gene editing</a>.</p>
<p>Here are three other fields where RNA is being investigated.</p>
<h2>Vaccines</h2>
<p>The mRNA vaccines that are used to protect against SARS-CoV-2 (the virus that causes COVID-19) are the first of their kind to be <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html">licensed for widespread human use</a>.</p>
<p>But studies and clinical trials on RNA vaccines for other viruses – and even cancers – have been <a href="https://clincancerres.aacrjournals.org/content/18/19/5460">going on for a decade</a>. These types of vaccines introduce a specific RNA sequence into the body, which causes the body’s ribosomes to temporarily express a specific, harmless viral protein (after which the foreign RNA molecules are degraded). In turn, this trains the immune system to respond in such a way that produces strong protection against this virus the next time it encounters it.</p>
<figure class="align-center ">
<img alt="A vial of the Pfizer-BioNTech vaccine." src="https://images.theconversation.com/files/393987/original/file-20210408-17-15he6mq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/393987/original/file-20210408-17-15he6mq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=393&fit=crop&dpr=1 600w, https://images.theconversation.com/files/393987/original/file-20210408-17-15he6mq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=393&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/393987/original/file-20210408-17-15he6mq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=393&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/393987/original/file-20210408-17-15he6mq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=494&fit=crop&dpr=1 754w, https://images.theconversation.com/files/393987/original/file-20210408-17-15he6mq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=494&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/393987/original/file-20210408-17-15he6mq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=494&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The mRNA vaccines that protect against COVID-19 are the first to be licensed for widespread use.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/new-york-ny-december-14-2020-1874434045">noamgalai/ Shutterstock</a></span>
</figcaption>
</figure>
<p>This is unlike conventional vaccines, which require either a harmless, inactive form of a virus, or small proteins or protein fragments made by a virus, to train the immune system. Designing and synthesising an RNA sequence that provides the body with instructions is also easily and quickly done.</p>
<p>But one of the biggest hurdles in making effective RNA-based drugs has been the relative instability of the molecules. These degrade rapidly when exposed to certain common enzymes and chemicals, so need to be kept at <a href="https://www.nature.com/articles/nrd.2017.243">very low temperatures</a> – in some cases <a href="https://www.bbc.co.uk/news/technology-54889084">below -70°C</a>, as required for the Pfizer vaccine.</p>
<h2>Diagnostic technologies</h2>
<p>RNA is also playing an expanding role in diagnostics. Research into <a href="https://link.springer.com/article/10.1007/s13238-020-00799-3">liquid biopsies</a> (which only require a sample of human body fluids, such as blood) have increasingly shown that by measuring levels of particular RNAs, many diseases can be diagnosed at an earlier stage – including cancers, neurodegenerative diseases and cardiovascular disease. </p>
<p>Alongside making it easier and less invasive to collect samples, RNA biomarkers have additional advantages over tissue biopsies and other, more invasive, collection methods – such as skin, organ, or bone biopsies – because they’re less painful and carry fewer risks.</p>
<p>Combinations of RNA biomarkers can also be simultaneously evaluated, allowing not only more confidence in a diagnosis, but even predictions of <a href="https://pubmed.ncbi.nlm.nih.gov/30735523/">disease progression and prognosis</a>. Large-scale studies that test the clinical suitability of these types of diagnostic tools are still needed however.</p>
<h2>Drug development</h2>
<p>RNA is also being used to help develop new drugs. </p>
<p>Drugs that target RNA can be identified, and in some instances customised, because researchers can sample RNA interactions and sequences linked to many different diseases from readily available databases. So far, drugs that target RNA have provided great promise in the treatment of very rare diseases, which <a href="https://www.nature.com/articles/d41573-020-00078-0">previously lacked effective, existing treatments</a> – such as Huntington’s disease.</p>
<p>Drugs are also being designed which can target RNAs and modify or inhibit the function of certain genes or protein production – including those responsible for many diseases and symptoms. Several of these have now been used to <a href="https://www.sciencedirect.com/science/article/pii/S2352320416000250">successfully treat viruses</a>, <a href="https://www.sciencedirect.com/science/article/pii/S1474442217302806">neurodegenerative diseases</a>, and even in <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa1813279">personalised medicine</a> (treatments designed specifically for that patient).</p>
<p>RNA interference drugs are another area of research. These drugs <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743327/">silence a specific gene</a> to treat a condition. Research into these types of drugs is currently underway for many conditions, including <a href="https://www.fda.gov/news-events/press-announcements/fda-approves-first-its-kind-targeted-rna-based-therapy-treat-rare-disease">amyloidosis</a> (a rare disease caused by a buildup of proteins in the body), <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa1807838">acute hepatic porphyria</a> (a rare metabolic disorder), and <a href="https://www.nature.com/articles/7700931/">several cancers</a> (including lung cancer).</p>
<p>More recently, certain groups of RNAs and proteins have been shown to change the sensitivity of diseases (<a href="https://academic.oup.com/nar/article/44/3/1227/2502712">particularly cancers</a>) to treatment. This has made <a href="https://pubmed.ncbi.nlm.nih.gov/31522610/">some cancers less resistant</a> to conventional treatment as a result. This could potentially provide a valuable new combination therapy for hard to treat diseases.</p>
<p>There has been <a href="https://www.nature.com/articles/d41573-020-00078-0">plenty of investment</a> into RNA therapeutics, and progress has been rapid over the last decade. With further clinical trials (testing safety and efficacy), and improving methods for making them at low costs and improving their stability, we can hope to soon see the results of this work – and have a whole new generation of medicines to use, which are more specialised and effective.</p><img src="https://counter.theconversation.com/content/158190/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Oliver Rogoyski 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>RNA was used to make COVID vaccines. Now it could lead to more personalised healthcare.Oliver Rogoyski, Postdoctoral Research Fellow, RNA Biology and Biochemistry, University of SurreyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1543372021-02-24T13:28:52Z2021-02-24T13:28:52ZEngineered viruses can fight the rise of antibiotic-resistant bacteria<figure><img src="https://images.theconversation.com/files/385365/original/file-20210219-21-1mfowzt.jpg?ixlib=rb-1.1.0&rect=62%2C12%2C8234%2C4117&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Bacteriophage (yellow) are viruses that infect and destroy bacteria (blue). </span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/bacteriophages-infecting-bacteria-royalty-free-illustration/1155266155?adppopup=true&uiloc=thumbnail_same_series_adp&uiloc=thumbnail_same_series_adp">Christoph Burgstedt/Science Photo Library,Getty Images</a></span></figcaption></figure><p>As the world fights the SARS-CoV-2 virus causing the COVID-19 pandemic, another group of dangerous pathogens looms in the background. The threat of <a href="https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance">antibiotic-resistant bacteria</a> has been growing for years and <a href="https://cddep.org/publications/tracking-global-trends-in-the-effectiveness-of-antibiotic-therapy-using-the-drug-resistance-index/">appears to be getting worse</a>. If COVID-19 taught us one thing, it’s that governments should be prepared for more global public health crises, and that includes finding new ways to combat rogue bacteria that are becoming resistant to commonly used drugs.</p>
<p>In contrast to the current pandemic, viruses may be be the heroes of the next epidemic rather than the villains. Scientists have shown that viruses could be <a href="https://doi.org/10.2147/IDR.S234353">great weapons</a> against bacteria that are resistant to antibiotics.</p>
<p>I am a <a href="https://www.kevindoxzen.com/">biotechnology and policy expert</a> focused on understanding how personal genetic and biological information can improve human health. Every person interacts intimately with a unique assortment of viruses and bacteria, and by deciphering these complex relationships we can better treat infectious diseases caused by antibiotic-resistant bacteria.</p>
<h2>Replacing antibiotics with phage</h2>
<p>Since the <a href="https://www.pbs.org/newshour/health/the-real-story-behind-the-worlds-first-antibiotic">discovery of penicillin in 1928</a>, antibiotics have changed modern medicine. These small molecules fight off bacterial infections by killing or inhibiting the growth of bacteria. The mid-20th century was called the <a href="https://doi.org/10.1038/nature17042">Golden Age</a> for antibiotics, a time when scientists were discovering dozens of new molecules for many diseases. </p>
<p>This high was soon followed by a <a href="https://doi.org/10.1016/j.mib.2019.10.008">devastating low</a>. Researchers saw that many bacteria were evolving resistance to antibiotics. Bacteria in our bodies were learning to evade medicine by evolving and mutating to the point that antibiotics no longer worked.</p>
<p>As an alternative to antibiotics, some researchers are turning to a natural enemy of bacteria: bacteriophages. <a href="https://theconversation.com/are-viruses-the-best-weapon-for-fighting-superbugs-111908">Bacteriophages</a> are viruses that infect bacteria. They outnumber bacteria <a href="https://doi.org/10.1002/bies.201000071">10 to 1</a> and are considered the most abundant organisms on the planet.</p>
<p>Bacteriophages, also known as phages, survive by infecting bacteria, replicating and bursting out from their host, which destroys the bacterium. </p>
<p>Harnessing the power of phages to fight bacteria isn’t a new idea. In fact, the first recorded use of so-called phage therapy was over a century ago. In 1919, <a href="https://doi.org/10.4161/bact.1.2.15845">French microbiologist Félix d'Hérelle</a> used a cocktail of phages to treat children suffering from severe dysentery.</p>
<p>D'Hérelle’s actions weren’t an accident. In fact, he is credited with <a href="https://doi.org/10.1155/2007/976850">co-discovering phages</a>, and he pioneered the idea of using bacteria’s natural enemies in medicine. He would go on to <a href="https://doi.org/10.3389/fmicb.2012.00238">stop cholera outbreaks in India and plague in Egypt</a>.</p>
<p>Phage therapy is not a standard treatment you can find in your local hospital today. But <a href="https://doi.org/10.1038/s41564-019-0666-4">excitement about phages</a> has grown over the past few years. In particular, scientists are using new knowledge about the complex relationship between phages and bacteria to improve phage therapy. By engineering phages to better target and destroy bacteria, scientists hope to overcome antibiotic resistance.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/385370/original/file-20210219-17-10em1jg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/385370/original/file-20210219-17-10em1jg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/385370/original/file-20210219-17-10em1jg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=303&fit=crop&dpr=1 600w, https://images.theconversation.com/files/385370/original/file-20210219-17-10em1jg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=303&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/385370/original/file-20210219-17-10em1jg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=303&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/385370/original/file-20210219-17-10em1jg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=381&fit=crop&dpr=1 754w, https://images.theconversation.com/files/385370/original/file-20210219-17-10em1jg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=381&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/385370/original/file-20210219-17-10em1jg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=381&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 allows biologists to edit genetic material and engineer organisms.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/structure-editing-medicine-concept-low-poly-royalty-free-illustration/1126485534?adppopup=true&uiloc=thumbnail_same_series_adp">LuckyStep48/iStock/Getty Images Plus</a></span>
</figcaption>
</figure>
<h2>Engineering phages</h2>
<p>Even if you are not a biologist, you may have heard of one type of bacterial immune system: CRISPR, which stands for <a href="https://doi.org/10.1146/annurev-biochem-072911-172315">Clustered Regularly Interspaced Short Palindromic Repeats</a>. This immune system helps bacteria store genetic information from viral infections. The bacteria then use that information to fight off future invaders, much as our own immune system can recognize a particular pathogen to fight off infection.</p>
<p>CRISPR proteins in bacteria <a href="https://doi.org/10.1146/annurev-biophys-062215-010822">locate and cut</a> specific sequences of DNA or RNA found in viruses. Such precise cutting also makes CRISPR proteins efficient tools for editing the genomes of various organisms. This is why the development of CRISPR genome-editing technology won the <a href="https://doi.org/10.1038/d41586-020-02765-9">Chemistry Nobel prize in 2020</a>.</p>
<p>Now scientists are hoping to use the knowledge about CRISPR systems to engineer phages to destroy dangerous bacteria.</p>
<p>When the engineered phage locates specific bacteria, the phage injects CRISPR proteins inside the bacteria, cutting and destroying the microbes’ DNA. Scientists have found a way to turn <a href="https://doi.org/10.1016/j.tibtech.2017.10.021">defense into offense</a>. The proteins normally involved in protecting against viruses are repurposed to target and destroy the bacteria’s own DNA. The scientists can specifically target the DNA that makes the bacteria resistant to antibiotics, making this type of phage therapy extremely effective.</p>
<p>The bacteria <em>Clostridioides difficile</em> is an antibiotic-resistant strain of bacteria that kills 29,000 people in the U.S. every year. In one demonstration of this CRISPR-based technique, researchers <a href="https://doi.org/10.1128/mBio.00019-20">engineered phages</a> to inject a molecule that directs the bacteria’s own CRISPR proteins to chew up the bacteria’s DNA like a paper shredder.</p>
<p>CRISPR isn’t the only bacterial immune system. Scientists are discovering more using creative microbiology experiments and advanced computational tools. They have already found <a href="https://doi.org/10.1038/s41587-020-0718-6">tens of thousands of new microbes</a> and <a href="https://doi.org/10.1126/science.aar4120">dozens of new immune systems</a>. Scientists hope to find more tools that could help them engineer phages to target a wider range of bacteria.</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>
<h2>Beyond the science</h2>
<p>Science is only half of the solution when it comes to fighting these microbes. Commercialization and regulation are important to ensure that this technology is in society’s toolkit for fending off a worldwide spread of antibiotic-resistant bacteria.</p>
<p>Multiple companies are engineering phages or identifying naturally occurring phages to destroy specific harmful bacteria. Companies like <a href="https://www.felixbt.com/">Felix Biotechnology</a> and <a href="https://cytophage.com/">Cytophage</a> are producing specialized bacteria-killing phages to replace antibiotics in human health and agriculture. <a href="https://www.biomx.com/">BiomX</a> aims to treat infections common in chronic diseases like cystic fibrosis and inflammatory bowel disease using both natural and engineered phage cocktails. Thinking globally, the company <a href="https://www.phageproinc.com/projects">PhagePro</a> is using phages to treat cholera. These deadly bacteria affect people primarily in Africa and Asia.</p>
<p>Alongside the commercialization of phage therapy, policies that facilitate safe testing and regulation of the technology are vital. To avoid replicating America’s poor COVID-19 response, I believe the world must invest in, engineer, and then test phage therapies. Proactive planning will help us combat whatever antibiotic-resistant bacteria might spread.</p><img src="https://counter.theconversation.com/content/154337/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kevin Doxzen is affiliated with Arizona State University and the World Economic Forum</span></em></p>As the world has focused on the COVID-19 pandemic, other microbial foes are waging war on humans. Antibiotic-resistant bacteria pose a growing threat. But viruses may defeat them.Kevin Doxzen, Hoffmann Postdoctoral Fellow, Arizona State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1491082021-02-15T14:31:11Z2021-02-15T14:31:11ZFive principles that should guide future DNA ‘editing’ in South Africa<figure><img src="https://images.theconversation.com/files/380676/original/file-20210126-15-1ertiyg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Any man-made changes to the human genome must be carefully regulated.</span> <span class="attribution"><span class="source">Billon Photos/Shutterstock</span></span></figcaption></figure><p>In recent years there have been several major innovations in genetics. One prominent example is <a href="https://theconversation.com/what-is-crispr-the-gene-editing-technology-that-won-the-chemistry-nobel-prize-147695">CRISPR-Cas9</a>, a novel biotechnology derived from bacteria that could be used to make precise changes to specific locations in the human genome – our DNA. </p>
<p>Scientists could use CRISPR-Cas9 and similar technologies to eliminate genetic diseases by using germline cells (gametes and embryos). This is known as germline editing; a child born from modified gametes or embryos will have such “edits” in their DNA and can pass those on to their future offspring. Of course, as with anything that relates to altering DNA, <a href="http://sajbl.org.za/index.php/sajbl/article/viewFile/636/626">controversy abounds</a>.</p>
<p>It is possible that germline editing will be ready for public use in the next decade. Currently, however, many <a href="https://doi.org/10.1186/1477-7827-12-108">countries lack rules on the use of this technology</a>. Therefore, it has been argued that this situation should be rectified to ensure that germline editing is governed by proper legal and ethical rules, although what these rules should be is heavily disputed.</p>
<p>In a <a href="https://www.sajs.co.za/article/view/6760">recent paper</a> published by the South African Journal of Science, we investigated the current regulatory framework for germline editing in South Africa. Quite simply, it is lacking and several gaps must be filled. We propose five principles that could guide a proper ethical and legal framework for this and similar technologies.</p>
<h2>The status quo</h2>
<p>There is a distinction between the rules relating to germline editing by scientists for the purpose of research, and germline editing for use in practice by the general public, known as clinical application.</p>
<p>South Africa’s regulatory environment that covers questions of ethics in medicine currently seems to not permit research on, and the clinical application of, human germline editing. This is according to ethics guidelines published by the <a href="https://www.sada.co.za/media/documents/HPCSA_Booklet_14_Biotechnology_Research_in_SA.pdf">Health Professions Council of South Africa</a> and the <a href="https://www.samrc.ac.za/sites/default/files/attachments/2016-06-29/ethicsbook2.pdf">South African
Medical Research Council</a> – although the justifications for this are unclear. </p>
<p>By contrast, the South African legal regulatory environment allows a regulatory path that would, in principle, permit research on human germline editing. This is because none of the current regulation on research using germline cells prohibits research for the purpose of germline editing. The legal regulation of the clinical application of human germline editing, on the other hand, is uncertain. </p>
<p>When it comes to research, there is currently no South African law that specifically regulates germline editing. It’s expected to comply with the same laws and ethical requirements as <a href="https://www.sajs.co.za/article/view/6760">all scientific research relating to human reproduction.</a>. This gap needs to be addressed through new regulations.</p>
<p>When it comes to germline editing as a clinical application, new regulations are required. But the wording will need to be nuanced because germline editing has long term, multi-generational effects that must be taken into account.</p>
<p>The new regulation will also have to manage gaps such as the fact that the practice is viewed under existing regulations as a hybrid of medicine and medical device.</p>
<p>Crucially, germline editing can only proceed if South African law doesn’t prohibit it. Some may argue that section 57 of the <a href="https://www.gov.za/documents/national-health-act">National Health Act</a>, which forbids the “reproductive cloning of a human being”, applies here – and so, they would suggest, germline editing is actually illegal. </p>
<hr>
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<strong>
Read more:
<a href="https://theconversation.com/why-the-case-against-designer-babies-falls-apart-45256">Why the case against designer babies falls apart</a>
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</em>
</p>
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<p>But we disagree with this line of argument. This provision was intended for the purpose of regulating cloning, and because germline editing is different from cloning, this section should not be interpreted as applying to germline editing. </p>
<p>Having considered all this, we propose that five guiding principles should steer future regulation of germline editing in South Africa.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/human-gene-editing-who-decides-the-rules-128434">Human gene editing: who decides the rules?</a>
</strong>
</em>
</p>
<hr>
<h2>Principles</h2>
<p><strong>Principle 1: Human germline editing should be regulated, not banned.</strong></p>
<p>Human germline editing for clinical application has the potential to improve people’s lives. It could, for instance, be used to prevent diseases. For this reason, it shouldn’t be ignored or banned; instead proper regulation that considers the potential long-term implications must be considered.</p>
<p><strong>Principle 2: Use the well-established standard of safety and efficacy.</strong> </p>
<p>Human germline editing clinical applications should only be made accessible to the public if they are proven to be safe and effective, including for future generations. This will mean that human clinical trials will have to be carried out. These are <a href="https://doi.org/10.1007/s11673-019-09947-9">challenging, but possible</a>.</p>
<p><strong>Principle 3: Non-therapeutic uses of germline editing may be permissible.</strong></p>
<p>Even among those who are in favour of germline editing, it is often claimed that such use should be limited exclusively to the ‘therapeutic’ in the form of preventing genetic diseases. This, <a href="http://sajbl.org.za/index.php/sajbl/article/viewFile/636/626">it is said</a>, makes it different from genetic ‘enhancement’ in the form of germline edits that are not done for the purpose of healing people, but benefiting them. An example of genetic enhancement would be an edit which made a child have a high IQ or greater athletic ability. </p>
<p>These are often viewed as morally reprehensible because they <a href="https://academic.oup.com/jlb/article/5/2/355/5036208">are reminiscent of the state-sponsored eugenics programmes</a> of early 20th century Britain, America and Nazi Germany. </p>
<p>It is important to note that state-enforced eugenic regimes used coercive means that violated procreative freedom. But individual uses of germline editing technologies promote procreative freedom by leaving their application up to individual choice. </p>
<p><strong>Principle 4: Respect parents’ reproductive autonomy.</strong></p>
<p>The choice to use safe and effective germline editing should be made by individual prospective parents because this choice is part of the parents’ right to make decisions concerning reproduction. The freedom to use new reproductive technologies like germline editing is one which falls under the protection of section 12(2)(a) of South Africa’s <a href="https://www.justice.gov.za/legislation/constitution/SAConstitution-web-eng.pdf">Constitution</a>. </p>
<p><strong>Principle 5: Promote the achievement of equality of access.</strong></p>
<p>New technology may only be accessible to the rich, worsening existing inequalities in society – particularly in societies like South Africa given the wide <a href="https://theconversation.com/south-africa-needs-to-fix-its-dangerously-wide-wealth-gap-66355">gap between the rich and poor</a>, and the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556866/">lack of access to healthcare</a> for the underprivileged. However, the possibility of inequality cannot be a reason to suppress the technology. Instead it should be a reason for measures to be taken that promote access for the underprivileged.</p><img src="https://counter.theconversation.com/content/149108/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Bonginkosi Shozi receives funding from the National Research Foundation and the UKZN African Health Research Flagship. </span></em></p><p class="fine-print"><em><span>Marietjie Botes receives funding from the UKZN African Health Law Research Flagship</span></em></p>We propose five principles that could guide a proper ethical and legal framework for germline editing and similar technologies.Bonginkosi Shozi, Doctoral Fellow with the UKZN African Health Research Flagship, University of KwaZulu-NatalMarietjie Botes, Post Doctoral Fellow, University of KwaZulu-NatalLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/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>
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<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>
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<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/1491642020-12-10T17:20:15Z2020-12-10T17:20:15ZMeet the Canadian writers and researchers who deserve to win the Nobel Prize<figure><img src="https://images.theconversation.com/files/374232/original/file-20201210-19-1pq1r1d.jpg?ixlib=rb-1.1.0&rect=39%2C15%2C5248%2C3504&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Margaret Atwood gives a talk at a Walrus magazine event in Toronto on June 14, 2016. </span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>This year, Nobel Prizes continued to celebrate women’s achievements: the <a href="https://doi.org/10.1038/d41586-020-02765-9">Nobel Prize in chemistry</a> <a href="https://www.nobelprize.org/prizes/chemistry/2020/summary">was awarded jointly to Emmanuelle Charpentier and Jennifer Doudna</a> for developing a tool for genomic editing called CRISPR-Cas9.</p>
<p>This builds on the 2018 chemistry prize which went to <a href="https://www.nobelprize.org/prizes/chemistry/2018/arnold/facts/">Frances Arnold</a> for her application of genetic engineering to create new proteins to benefit humanity. And in physics, <a href="https://www.nobelprize.org/prizes/physics/2020/ghez/facts/">Andrea Ghez</a> received the award for the discovery of a black hole in the centre of the Milky Way. Canada’s own <a href="https://www.nobelprize.org/prizes/physics/2018/summary/">Donna Strickland</a> received the Nobel in 2018.</p>
<p>With the Nobel in literature going to Canada’s <a href="https://www.nobelprize.org/prizes/literature/2013/munro/facts/">Alice Munro</a> in 2013 and this year’s award to American <a href="https://www.nobelprize.org/prizes/literature/2020/summary/">Louise Gluck</a>, Canadians eagerly await even further recognition for <a href="https://thebookerprizes.com/booker-prize/news/margaret-atwood-and-bernardine-evaristo-winners-2019-booker-prize-announced">Margaret Atwood</a>, a double winner of the Booker prize. </p>
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<a href="https://images.theconversation.com/files/372026/original/file-20201130-23-1iuvkxo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="The author Alice Munro reads from her book while sitting next to a large replica of the $5 coin celebrating her achievements." src="https://images.theconversation.com/files/372026/original/file-20201130-23-1iuvkxo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/372026/original/file-20201130-23-1iuvkxo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/372026/original/file-20201130-23-1iuvkxo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/372026/original/file-20201130-23-1iuvkxo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/372026/original/file-20201130-23-1iuvkxo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/372026/original/file-20201130-23-1iuvkxo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/372026/original/file-20201130-23-1iuvkxo.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">Nobel Prize-winning Canadian author Alice Munro reads from her book ‘The View From Castle Rock’ at a ceremony held by the Royal Canadian Mint to celebrate her win at the Great Victoria Public Library in Victoria, B.C., on March 24, 2014.</span>
<span class="attribution"><span class="source">(THE CANADIAN PRESS/Chad Hipolito)</span></span>
</figcaption>
</figure>
<p>Several women in Canada have made <a href="https://www.healthing.ca/science/o-canada-a-look-at-canadian-health-innovation">Nobel-worthy discoveries in the area of life sciences</a>. None may be more deserving than McGill University’s Brenda Milner for her discoveries on long-term memory. </p>
<p>It is not only women in Canada whose contributions should be recognized with more Nobel Prizes, there is a strong case for men as well. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/a-memory-pill-cognitive-neurosciences-contributions-to-the-study-of-memory-109707">A memory pill? Cognitive neuroscience's contributions to the study of memory</a>
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</em>
</p>
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<h2>Canadian pride</h2>
<p>This year’s Nobel Prize in physiology or medicine went to the University of Alberta’s <a href="https://www.ualberta.ca/michael-houghton-nobel-prize-2020.html">Michael Houghton</a> for his discovery of hepatitis C. In 2015, the Nobel Prize in physics went to Arthur McDonald at Queen’s University, for his <a href="https://www.nobelprize.org/prizes/physics/2015/mcdonald/facts/">discovery that neutrinos have mass</a>.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-an-alberta-researchers-discovery-of-hepatitis-c-led-to-the-nobel-prize-and-saved-lives-147553">How an Alberta researcher’s discovery of hepatitis C led to the Nobel Prize and saved lives</a>
</strong>
</em>
</p>
<hr>
<p>Canada aspires to even further recognition for the discovery of bacterial adaptive immunity by <a href="https://www.moineau.bcm.ulaval.ca/index.php?id=2&L=3">Sylvain Moineau</a> at Laval University that was the foundation for this year’s Nobel Prize in chemistry. </p>
<p>Together with <a href="https://cals.ncsu.edu/food-bioprocessing-and-nutrition-sciences/people/rbarran/">Rodolphe Barrangou</a> at North Carolina State University and <a href="https://www.dupontnutritionandbiosciences.com/news/dupont-scientist-philippe-horvath-receives-franklin-institute-science-prize-2018-bower-award-for-groundbreaking-research-on-crispr-cas.html">Philippe Horvath</a> at Dupont Nutrition and Health in France, they demonstrated that CRISPR-Cas9 is the adaptive immune system of bacteria. </p>
<p><a href="https://dx.doi.org/10.1042/EBC20160017">Adaptive immunity</a> has been long understood in vertebrates as the acquisition of memory of past infections from a pathogen. Any subsequent infection leads to destruction of the pathogen. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/why-cant-canada-win-another-nobel-prize-in-medicine-87910">Why can't Canada win another Nobel Prize in medicine?</a>
</strong>
</em>
</p>
<hr>
<p>Barrangou, Horvath and Moineau’s interest was in yogurt, and specifically why <a href="https://doi.org/10.1186/1475-2859-10-S1-S20">bacteria used to make yogurt died from viral infections</a>. Moineau is an expert on bacterial viruses known as bacteriophages. Barrangou and Horvath are food scientists. Together, they discovered that bacteria could resist viral infections by an adaptive immune system that had <a href="http://doi.org/10.1126/science.1138140">a memory of past bacteriophage infections</a> and a <a href="https://www.nature.com/articles/nature09523">mechanism to destroy any subsequent infections</a>. These discoveries extended the concept of adaptive immunity from vertebrates to bacteria.</p>
<p>They discovered the memory of past viral infections in bacteria is CRISPR. They also discovered that any subsequent infection would be destroyed by the bacterial enzyme Cas9. It is <a href="https://doi.org/10.1038/nbt.3659">these discoveries</a> that enabled Charpentier and Douda to create the tool kit of CRISPR-Cas9 to edit genes in any organism. </p>
<p>By 2010, more than 10 Nobel Prizes in physiology or medicine had been given for <a href="https://www.nobelprize.org/prizes/uncategorized/nobel-prizes-and-the-immune-system/">discoveries of immune systems</a> with <a href="https://www.nobelprize.org/prizes/medicine/2011/summary/">three more in 2011</a>. Recognizing Barrangou, Horvath and Moineau with a Nobel Prize for their demonstration of adaptive immunity in bacteria is more than a hope.</p>
<p><em>John Bergeron gratefully acknowledges Kathleen Dickson as co-author.</em></p><img src="https://counter.theconversation.com/content/149164/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>John Bergeron 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>Canada has produced Nobel Prize winners in the arts and sciences. With several recent awards, Canadian talent still has the potential for future achievements.John Bergeron, Emeritus Robert Reford Professor and Professor of Medicine, McGill UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1513132020-12-07T13:24:31Z2020-12-07T13:24:31ZEditing the DNA of human embryos could protect us from future pandemics<figure><img src="https://images.theconversation.com/files/373292/original/file-20201207-15-iedm1d.jpg?ixlib=rb-1.1.0&rect=60%2C60%2C6720%2C4365&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">We could edit our genes to make us more resistance to viruses.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/researcher-working-dna-on-blurred-background-1106986568"> Natali_ Mis/Shutterstock</a></span></figcaption></figure><p>Hollywood blockbusters such as <a href="https://www.imdb.com/title/tt0120903/">X-men</a>, <a href="https://www.imdb.com/title/tt0119177/">Gattaca</a> and <a href="https://www.imdb.com/title/tt0369610/">Jurassic World</a> have explored the intriguing concept of “germline genome editing” – a biomolecular technique that can alter the DNA of sperm, eggs or embryos. If you remove a gene that causes a certain disease in an embryo, not only will the baby be free of the disease when born – so will its descendants. </p>
<p>The technique is, however, controversial – we can’t be sure how a child with an altered genome will develop over a lifetime. But with the COVID-19 pandemic showing just how vulnerable human beings are to disease, is it time to consider moving ahead with it more quickly?</p>
<p>There’s now good evidence that the technique works, with research normally carried out on unviable embryos that will never result in a living baby. But in 2018, Chinese scientist He Jiankui claimed that the first gene-edited babies <a href="https://www.ncbi.nlm.nih.gov/books/NBK535994/">had indeed been born</a> – to the <a href="https://theconversation.com/worlds-first-gene-edited-babies-premature-dangerous-and-irresponsible-107642">universal shock</a>, criticism and intrigue of the scientific community.</p>
<p>This human germline genome editing (hGGe) was performed using the <a href="https://theconversation.com/nobel-prize-two-women-share-chemistry-prize-for-the-first-time-for-work-on-genetic-scissors-147721">Nobel-prize winning CRISPR system</a>, a type of molecular scissors that can cut and alter the genome at a precise location. Researchers and policy makers in the fertility and embryology space agree that it is a matter of “when” and not “if” hGGe technologies will become available to the general public.</p>
<p>In 2016, the UK became the first country in the world to formally permit “<a href="https://theconversation.com/worlds-first-three-parent-baby-raises-questions-about-long-term-health-risks-66189">three-parent babies</a>” using a genetic technique called mitochondrial replacement therapy – replacing unhealthy mitochondria (a part of the cell that provides energy) with healthy ones from a donor.</p>
<h2>COVID-19 protection</h2>
<p>Scientists are now discussing genome editing <a href="https://www.wired.com/story/could-crispr-be-the-next-virus-killer/">in the light of the
COVID-19 pandemic</a>. For example, one could use CRISPR <a href="https://www.fiercebiotech.com/research/stanford-team-deploys-crispr-gene-editing-to-fight-covid-19">to disable coronaviruses</a> by scrambling their genetic code. But we could also edit people’s genes to make them more resistant to infection – for example by targeting “T cells”, which are central in the body’s immune response. There are already CRISPR clinical trials underway that look to <a href="https://science.sciencemag.org/content/367/6481/eaba7365">genome edit T cells in cancer patients</a> to improve anti-tumour immunity (T cells attacking the tumour). </p>
<p>This type of gene editing differs to germline editing as it occurs in non-reproductive cells, meaning genetic changes are not heritable. In the long term, however, it may be more effective to improve T-cell responses using germline editing.</p>
<p>It’s easy to see the allure. The pandemic has uncovered the brutal reality that the majority of countries across the world are completely ill equipped to deal with sudden shocks to their, often, already overstretched healthcare systems. Significantly, the healthcare impacts are not only felt on COVID patients. Many cancer patients, for instance, have struggled to access treatments or diagnosis appointments in a timely manner during the pandemic.</p>
<p>This also raises the possibility of using hGGe techniques to tackle serious diseases such as cancer to protect healthcare systems against future pandemics. We already have a wealth of information that suggests certain gene mutations, such as those in the BRCA2 gene in women, increase the probability of cancer development. These disease genetic hotspots <a href="https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet">provide potential targets</a> for hGGe therapy. </p>
<p>Furthermore, healthcare costs for diseases such as cancer will continue to rise as drug therapies continue to become more personalised and targeted. At this point, wouldn’t gene editing be simpler and cheaper? </p>
<h2>Climate change and malaria</h2>
<p>As we approach the mezzo point of the 21st century, it is fair to say that COVID-19 could prove to be just the start of a string of international health crises that we encounter. A <a href="https://ipbes.net/pandemics">recent report</a> by the UN Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) emphasised the <a href="https://theconversation.com/why-are-emerging-viruses-here-and-why-now-29311">clear connection</a> between global pandemics and the loss of biodiversity and climate change. Importantly, the report delivers the grim future prediction of more frequent pandemics, which may well be deadlier and more devastating than COVID-19. </p>
<p>It isn’t just more viral pandemics that we might have to face in the future. As our global climate changes, so will the transmission rates of other diseases such as malaria. If malaria begins presenting itself in locations with unprepared healthcare systems, the impacts on healthcare provision could be overwhelming. </p>
<p>Interestingly, there is a way to protect people from malaria – introducing a single faulty gene for the sickle cell anaemia. One copy of this faulty gene gives you <a href="https://www.newscientist.com/article/dn20450-how-sickle-cell-carriers-fend-off%20malaria/#:%7E:text=People%20develop%20sickle%2Dcell%20disease,confers%20some%20resistance%20to%20malaria">a level of protection against malaria</a>. But if two people with a single faulty gene have a baby, the child could develop sickle cell anaemia. This shows just how complicated gene editing can be – you can edit genes to protect a population against one disease, but potentially causing trouble in other ways.</p>
<p>Despite the first hGGe humans already having been born, the reality is that the technique won’t be entering our mainstream lives any time soon. The UK Royal Society <a href="https://royalsociety.org/news/2020/09/heritable-genome-editing-report/">recently stated</a> that heritable genome editing is not ready to be tried in humans safely, although it has urged that if countries do approve hGGe treatment practices, it should focus on specific diseases that are caused by single specific genes, such as sickle cell anaemia and cystic fibrosis. But, as we have seen, it may not make sense to edit out the former in countries with high rates of malaria.</p>
<p>Other major challenges for researchers is unintended genetic modifications at specific sites of the genome which this could lead to a host of further complications to the genome network. The equitable access of treatment provides another sticking point. How would hGGe be regulated and paid for? </p>
<p>The world is not currently ready for hGGe technologies and any progress in this field is likely to occur at a very incremental pace. That being said, this technology will eventually come to feature in humanity for disease prevention. The big question is simply “when?”. Perhaps the answer depends on the severity and frequency of future health crises.</p><img src="https://counter.theconversation.com/content/151313/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Yusef Paolo Rabiah does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>We could start making our genomes equipped to deal with more frequent pandemics. But it may come at a cost.Yusef Paolo Rabiah, PhD Candidate at UCL Science, Technology, Engineering and Public Policy, UCLLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1468242020-11-10T13:22:30Z2020-11-10T13:22:30ZFlaws emerge in modeling human genetic diseases in animals<figure><img src="https://images.theconversation.com/files/367575/original/file-20201104-17-pvbobd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">This confocal microscope image shows the face of a week-old zebrafish.</span> <span class="attribution"><a class="source" href="https://sites.usc.edu/crumplab/files/2020/10/endoderm_facial_view.jpg">Peter Fabian and Gage Crump</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span></figcaption></figure><p><a href="https://crumplab.usc.edu/">My lab</a>, based at the University of Southern California Keck School of Medicine, uses zebrafish to model human birth defects affecting the face. When I tell people this, they are often skeptical that fish biology has any relevance to human health. </p>
<p>But zebrafish have backbones like us, contain by and large the same types of organs, and, critically for genetic research, share many genes in common. <a href="https://crumplab.usc.edu/">My group</a> has exploited these genetic similarities to create zebrafish models for several human birth defects, including <a href="https://doi.org/10.7554/eLife.37024">Saethre-Chotzen Syndrome</a>, in which the bones of the skull abnormally fuse together, and <a href="https://doi.org/10.7554/eLife.16415">early-onset arthritis</a>.</p>
<p>Similar to fish, our bodies develop under the control of about 25,000 genes. The trick is finding out what each gene does. Stunning advances such as CRISPR-based molecular scissors, for which the Nobel Prize in chemistry was just awarded, allow us to precisely change genes, and designer chemicals can silence particular genes. In a recent <a href="https://doi.org/10.1038/s41586-020-2674-1">study from our group published in Nature</a>, however, we find that these tools are still far from perfect. Although CRISPR now allows us to efficiently generate lab animals that can pass human disease mutations onto the next generation, claims that simply injecting CRISPR into embryos or silencing genes with designer chemicals can accurately model human genetic disease are being questioned. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/367316/original/file-20201103-21-jx48ma.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/367316/original/file-20201103-21-jx48ma.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/367316/original/file-20201103-21-jx48ma.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=431&fit=crop&dpr=1 600w, https://images.theconversation.com/files/367316/original/file-20201103-21-jx48ma.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=431&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/367316/original/file-20201103-21-jx48ma.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=431&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/367316/original/file-20201103-21-jx48ma.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=542&fit=crop&dpr=1 754w, https://images.theconversation.com/files/367316/original/file-20201103-21-jx48ma.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=542&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/367316/original/file-20201103-21-jx48ma.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=542&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 humble zebrafish, <em>Danio rerio</em>, is used as a model organism to study human genetics.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/8659392@N07/13896905021/in/photolist-nb2gGH-G2ScJv-2jjF4ny-fKsrZj-Gh96nd-27zGH-bAQzDd-7hHx8W-4JwFeR-wjvq8x-28vbY3h-29SNmC8-29SNmEc-29SNmyk-2bgeoH6-63teZG-7A8YxQ-63oZAZ-7A8YHf-uZWQwM-jLsrGe-5JMzv7-5JMzrE-69ouFc-7A8YC9-HJ4qwU-M6kcwF-ManLk3-ManLr5-ManLqJ-MdvuxM-GiJrnF-vDZ63w-2ABVas-29SNmGM-cv2sYC-FZzffQ-RNFgU4-2joUawt-CUP2xW-cv2sSG-HZxm4U-2bbQFJS-GyaCKH-nZXkb6-Mdvqdp-2eoJxrZ-Sau7dT-Sau73x-s4ukxf">Tohru Murakami</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<h2>Emergence of zebrafish as a model for human genetic disease</h2>
<p>Finding the precise mutation that causes a particular birth defect or a late-onset disease can be tedious work. The human genome is made up of 3 billion building blocks called DNA nucleotides, and changing just one of these can cause devastating birth defects. </p>
<p>To figure out if we have identified the right disease-causing mutation in humans, we typically engineer the same change into the genome of a lab animal. We then breed these animals to generate babies with the disease mutation and look for the appearance of defects similar to those in human patients. </p>
<p>We study zebrafish because they are small, which means we can grow thousands of different genetically modified animals. We routinely use CRISPR to engineer fish that pass on a gene-breaking mutation to the next generation.</p>
<p>We then study the appearance of defects similar to those in humans lacking these genes – in essence creating personalized zebrafish avatars of genetic disease. As zebrafish embryos are transparent and develop rapidly outside the mother, they are particularly useful for understanding how human disease mutations disrupt normal development. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/367311/original/file-20201103-19-1lf2dwk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/367311/original/file-20201103-19-1lf2dwk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/367311/original/file-20201103-19-1lf2dwk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/367311/original/file-20201103-19-1lf2dwk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/367311/original/file-20201103-19-1lf2dwk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/367311/original/file-20201103-19-1lf2dwk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/367311/original/file-20201103-19-1lf2dwk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/367311/original/file-20201103-19-1lf2dwk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">At the NHGRI Zebrafish Core, the largest zebrafish facility in the country, researcher Kevin Bishop holds up a tank of zebrafish to observe their behavior and physiology.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/genomegov/27386588184/in/photolist-HJ4qwU-M6kcwF-ManLk3-ManLr5-ManLqJ-MdvuxM-GiJrnF-vDZ63w-2ABVas-29SNmGM-cv2sYC-FZzffQ-RNFgU4-2joUawt-CUP2xW-cv2sSG-HZxm4U-2bbQFJS-GyaCKH-nZXkb6-Mdvqdp-2eoJxrZ-Sau7dT-Sau73x-s4ukxf-BDzA8L-wBu5Uz-2H2dKd-BDzxHq-2izBEnk-2joUoQs-CrwK1d-2iXYiw3-2iXWyFK-GTgkWF-9s8y9c-2jvFNid-BDGZ3t-rrTDWn-2joQbmP-cv2sU5-2joTaEq-dV3KHa-CB6kCz-f3rtso-29SNmPF-2jvELJc-2jvFU8E-2jvFU1R-2bgeoMz/">Ernesto del Aguila III, NHGRI</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>In the race for speed, problems emerge</h2>
<p>Even in zebrafish, engineering animals to lack particular genes can be a time-consuming process. In my lab, we first create gene mutations in embryos, grow these fish to adulthood and then breed fish together to look at defects in the next generation. </p>
<p>This whole process can take a year or longer. Unsurprisingly, many labs are attempting shortcuts. Some are injecting large quantities of CRISPR molecular scissors into animals and then looking for defects in these same animals. Others are using chemicals to turn off, or silence, genes in the embryo rather than permanently changing the genes. </p>
<p>More and more frequently <a href="https://doi.org/10.1016/j.devcel.2014.11.018">studies</a> like this are calling into question the accuracy of these shortcuts. In animals that have been injected with CRISPR molecular scissors, not every cell is changed in the same way. And the chemicals used to silence genes appear to have unintended consequences, poisoning the embryo in a generic way.</p>
<p>For example, <a href="https://doi.org/10.1038/nature23454">researchers in Spain</a> recently reported that a gene called prrx1a was critical for the proper development of the heart. To figure this out, they silenced prrx1a in zebrafish with chemicals. Then, in a second experiment, they injected CRISPR molecular scissors into zebrafish embryos and examined them just one day later for heart defects. </p>
<p>In contrast, <a href="https://doi.org/10.1038/s41586-020-2674-1">we completely removed the prrx1a gene</a> and looked at generations of fish lacking this gene. Hearts in these mutant fish developed perfectly normally, showing that prrx1a was not critical for heart development. Instead, we showed that the heart defects seen upon chemical treatment in the Spanish study were due to a general poisoning of the embryos unrelated to the prrx1a gene. Animals simply injected with CRISPR also showed defects not seen upon complete removal of the prrx1a gene, <a href="https://doi.org/10.1038/s41586-020-2675-0">although the exact reasons for these differences remain a source of active debate</a>.</p>
<p>And not just our group has noticed these flaws. Using similar gene removal as we reported, <a href="https://doi.org/10.1242/dev.193029">the group led by Didier Stainier</a> refuted a study that had used CRISPR injection and gene silencing to link the tek gene to blood vessel development. Given the number of studies relying on gene silencing in lab animals, as opposed to engineering the DNA mutations, the causative genes for many human diseases may need to be reevaluated. </p>
<h2>A path forward with improved genome engineering</h2>
<p>The desire for speed in research must not come at a cost of accuracy and reproducibility. </p>
<p>The good news is that, with the ease of CRISPR, we now know how to engineer the right types of mutations in lab animals to validate human disease mutations. By creating lab animals such as zebrafish that have the mutations engineered into their genomes and then observing whether their offspring develop the same diseases as patients with the mutations, we can be confident in having identified the right human disease gene. </p>
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<p>Getting it right is important for accurately counseling prospective parents of their genetic risks for certain birth defects, as well as identifying the relevant genes that can be targeted to prevent or even reverse disease. </p>
<p>Science is constantly evolving. While the ability to engineer the genome with CRISPR is opening up endless possibilities for human genetics, researchers must also recognize the limitations of new technologies. Although rapid, directly injecting CRISPR or silencing genes with chemicals gives misleading results too often. In order to confidently identify causative mutations linked to human disease, we will need to continue to study lab animals engineered to carry and pass on the same DNA changes as found in human patients.</p><img src="https://counter.theconversation.com/content/146824/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gage Crump receives funding from the National Institute of Health and has previously received funding from the California Institute of Regenerative Medicine and March of Dimes. </span></em></p>Recent studies using CRISPR to fast-track genetic studies into human disease genes appear flawed.Gage Crump, Professor of Stem Cell Biology and Regenerative Medicine, University of Southern CaliforniaLicensed as Creative Commons – attribution, no derivatives.