tag:theconversation.com,2011:/africa/topics/genetic-diseases-6338/articlesGenetic diseases – The Conversation2024-02-28T16:00:10Ztag:theconversation.com,2011:article/2243852024-02-28T16:00:10Z2024-02-28T16:00:10ZLosing their tails provided our ape ancestors with an evolutionary advantage – but we’re still paying the price<figure><img src="https://images.theconversation.com/files/578565/original/file-20240228-27-5jpovx.jpg?ixlib=rb-1.1.0&rect=41%2C5%2C3417%2C2504&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Unlike humans, many animals still have tails.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/monkey-zoo-game-asking-food-46190563">vblinov/Shutterstock</a></span></figcaption></figure><p>Put the word “evolution” into Google images and the results are largely variations on one theme: Ralph Zallinger’s illustration, <a href="https://theconversation.com/evolution-that-famous-march-of-progress-image-is-just-wrong-132536">March of Progress</a>. Running left to right, we see a chimp-like knuckle walker gradually becoming taller and standing erect. </p>
<p>Implicit in such images – and the title of the picture – are biases in common views of evolution: that we are some sort of peak, the perfected product of the process. We imagine we are indeed the fittest survivors, the very best we can be. But seen that way, there’s a paradox. If we are so amazing, how come so many of us suffer from developmental or genetic diseases? </p>
<p>A new study, <a href="https://www.nature.com/articles/s41586-024-07095-8">published in Nature</a>, provides an explanation for our error-prone early development by looking at the genetic changes that enabled our ancestors to lose their tails.</p>
<p>Current estimates suggest that about half of all fertilised eggs never even make it to be <a href="https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3001671">recognised pregnancies</a> and that for every child born about <a href="https://www.biorxiv.org/content/10.1101/372193v1.full">two never made it to term</a>. In fish and amphibians, such <a href="https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3001671">early death is unheard of</a>. Of those of us lucky enough to be born, <a href="https://www.nature.com/articles/s41431-019-0508-0">a little under 10%</a> will suffer one of the many thousand “rare” genetic diseases, such as haemophilia. The not so rare diseases, such as sickle cell disease and cystic fibrosis, affect yet more of us. </p>
<p>Surely this wouldn’t be the case in an evolutionary successful species? Where is the progress? </p>
<p>There are multiple possible solutions to this problem. One is that, compared to other species, we have an unusually high mutation rate. There’s a relatively high likelihood that in your DNA there will be a change that wasn’t inherited by either your mother or father. You were probably born with between ten and 100 such new changes to your DNA. For most other species that number is under one – often far under one. </p>
<h2>The genetics of tails</h2>
<p>There are other solutions too. One of the more obvious differences between us and many primate relatives is that we don’t have a tail. The loss of the tail happened <a href="https://onlinelibrary.wiley.com/doi/epdf/10.1002/jez.b.21029">around 25 million years ago</a> (for comparison our common ancestor with chimps was about 6 million years ago). We still have the coccyx as an evolutionary hangover from this tail-bearing ancestry. </p>
<p>Tail loss occurred in our ape ancestors at the same time as the evolution of a more erect back and, in turn, a tendency to use only two of the four limbs to support the body. While we can speculate on why these evolutionary changes may be coupled, that doesn’t address the problem of how (rather than why) tail-loss evolved: what were the underlying genetic changes?</p>
<p>The recent study looked at just that question. It identified an intriguing genetic mechanism. Many genes combine to enable the development of the tail in mammals. The team identified that primates without a tail had one additional “jumping gene” – sequences of DNA that can transfer to new areas of a genome – in a one such tail-determining gene, <em>TBXT</em>.</p>
<p>Much more of our DNA is the remains of such jumping genes than is sequence specifying proteins (the classical function of genes), so the gain of a jumping gene is nothing special. </p>
<h2>Evolutionary cost</h2>
<p>What was unusual was the effect that this new addition had. The team also identified that the same primates also had an older but similar jumping gene just a little bit of a distance away in the DNA also embedded within the TBXT gene. </p>
<p>The effect of these two in close proximity was to alter the processing of the resulting TBXT messenger RNA (molecules created from DNA that contain instructions for how to make proteins). The two jumping genes can stick to each other in the RNA, causing the block of RNA between them to be excluded from the RNA that gets coded into protein, resulting in a shorter protein.</p>
<p>To see the effect of this unusual exclusion, the team genetically mimicked this situation in mice by making a version of the mouse <em>Tbxt</em> gene that was also missing the excluded section. And indeed, the more of the form of the RNA with the section of the gene excluded, the more likely that the mouse would be born without a tail.</p>
<p>We have then a strong candidate for a mutational change that underpins the evolution of being tailless. </p>
<p>But the team noticed something else odd. If you make a mouse with only the form of the <em>Tbxt</em> gene with the section excluded, they can develop a condition that closely resembles the human condition spina bifida (when the spine and spinal cord fail to develop properly in the womb, causing a gap in the spine). Mutations in human <em>TBXT</em> had previously been <a href="https://academic.oup.com/hmg/article/5/5/669/2568755">implicated in this condition</a>. Other mice had other defects in the spine and spinal cord.</p>
<p>The team suggest that just as the coccyx is an evolutionary hangover of the evolution of being tailless that we all have, so too spina bifida may be a rare hangover resulting from the disruption to the gene that underpins our lack of a tail. </p>
<p>Being tailless, they suggest, was a large advantage, and so an increase in incidences of spina bifida was still worth it. This may be the case for many genetic and development diseases – they are an occasional byproduct of some mutation that on balance helped us. Recent work, for example, finds that the genetic variants that help us fight pneumonia also predispose us to <a href="https://www.sciencedirect.com/science/article/pii/S0002929723000526?via%3Dihub">Crohn’s disease</a> . </p>
<p>This goes to show how misleading the march of progress really can be. Evolution can only deal with the variation that is present at any time. And, as this latest study shows, many changes also come with costs. Not so much a march as a drunken stumbling.</p><img src="https://counter.theconversation.com/content/224385/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Laurence D. Hurst receives funding from European Research Council to examine the relationships between evolution and medicine. He is also an author of a book on the same subject and is on the scientific advisory board of ExpressionEdits. </span></em></p>Many evolutionary changes also come with costs.Laurence D. Hurst, Professor of Evolutionary Genetics at The Milner Centre for Evolution, University of BathLicensed 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>
<figure class="align-center ">
<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">
<figcaption>
<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>
</figcaption>
</figure>
<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>
<figure class="align-center zoomable">
<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>
</figcaption>
</figure>
<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>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/565889/original/file-20231214-21-z2b726.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/565889/original/file-20231214-21-z2b726.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/565889/original/file-20231214-21-z2b726.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=434&fit=crop&dpr=1 600w, https://images.theconversation.com/files/565889/original/file-20231214-21-z2b726.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=434&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/565889/original/file-20231214-21-z2b726.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=434&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/565889/original/file-20231214-21-z2b726.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=546&fit=crop&dpr=1 754w, https://images.theconversation.com/files/565889/original/file-20231214-21-z2b726.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=546&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/565889/original/file-20231214-21-z2b726.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=546&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<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>
</figcaption>
</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/2008032023-04-19T12:47:07Z2023-04-19T12:47:07ZErasing or replacing errors in a patient’s genetic code can treat and cure some genetic diseases<figure><img src="https://images.theconversation.com/files/512982/original/file-20230301-20-1v7gbc.jpg?ixlib=rb-1.1.0&rect=187%2C123%2C1762%2C1212&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Gene editing may hold promise for curing some diseases.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/concept-of-treatment-and-adjustment-of-dna-royalty-free-image/1316503044?phrase=gene%20editing&adppopup=true">Natali_Mis/iStock via Getty Images Plus</a></span></figcaption></figure><p><em>Genetic diseases can have devastating consequences for the people who inherit them. In recent years, scientists have found that there are human genetic diseases that might be treatable, and perhaps even curable, through gene editing. Gene editing is the process by which sections of a person’s DNA are altered. Commonly compared to a word processor or a pencil and eraser, precision gene editing agents can alter sections of a person’s genome to correct “misspellings,” or mutations, in their DNA.</em> </p>
<p><em><a href="https://chemistry.harvard.edu/people/david-r-liu">David Liu</a> is a professor of natural sciences at Harvard University. He co-founded several biotechnology companies including Prime Medicine, Beam Therapeutics, Editas Medicine, Chroma Medicine, Pairwise Plants, Exo Therapeutics, Resonance Medicine, and Nvelop Therapeutics. Liu and his team pioneered <a href="https://doi.org/10.1038/nature17946">base</a> editing and <a href="https://doi.org/10.1038/s41586-019-1711-4">prime</a> editing, two new innovative methods of gene editing that allow for precise alterations to a person’s genetic code.</em></p>
<p><em>In March, Liu’s video was shared with participants at the 2023 <a href="https://www.imaginesolutionsconference.com/">Imagine Solutions Conference</a> in Naples, Florida, about how gene editing works, why it is important, and the strides he and his team have made in the field so far.</em> </p>
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<figcaption><span class="caption">David Liu speaking at the Imagine Solutions 2023 Conference.</span></figcaption>
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<p><strong>What is gene editing, and why are scientists interested in developing and using this tool?</strong></p>
<p><a href="https://www.genome.gov/about-genomics/policy-issues/what-is-Genome-Editing">Gene editing</a> is a technique that makes it possible to purposefully change genes in the <a href="https://medlineplus.gov/genetics/understanding/basics/dna/">DNA</a> of different organisms, including <a href="https://doi.org/10.3390/ijms21165665">crops</a> and <a href="https://doi.org/10.1080/19768354.2020.1726462">animals</a>. Scientists are interested in developing and using genome editors because they are powerful tools for studying biology, treating human diseases and <a href="https://doi.org/10.3389/fsufs.2021.685801">improving agriculture</a>. More than <a href="https://clinicaltrials.gov">50 clinical trials</a> using gene editing to treat a variety of disorders are in progress.</p>
<p>According to the U.S. <a href="https://www.genome.gov/dna-day/15-ways/rare-genetic-diseases">National Human Genome Research Institute</a>, around 280 million individuals worldwide live with a rare genetic disease. Most of these individuals have few to no treatment options, leaving them resigned to their genetic fate.</p>
<p><strong>Can you explain the difference between base and prime editing? Why would scientists use one over the other?</strong></p>
<p>Neither <a href="https://doi.org/10.1038/s41573-020-0084-6">base editors</a> nor <a href="https://doi.org/10.1038/s41434-021-00263-9">prime editors</a> exist in nature; instead, both were engineered in our laboratory from natural and laboratory-evolved components. </p>
<p><a href="https://doi.org/10.1038/nature17946">Base editing</a>, often compared to a pencil and eraser, can precisely and efficiently correct <a href="https://doi.org/10.1038/nature24644">four of the most common types of misspellings</a> that occur in DNA, together accounting for about 30% of all known disease-causing DNA errors. Base editors perform a chemical reaction on an individual DNA letter, or “base,” rearranging its atoms to instead become a different DNA base. But base editing cannot be used to correct mistakes such as extra letters, missing letters or the remaining types of single-letter misspellings in DNA. </p>
<p>In contrast, <a href="https://doi.org/10.1038/s41586-019-1711-4">prime editors</a>, sometimes compared to the “search and replace” feature in a word processor, can replace any stretch of up to hundreds of DNA letters with virtually any other sequence of letters. In theory, the versatility of prime editing makes it possible to correct most known DNA misspellings that cause disease by restoring the typical DNA sequence. </p>
<p>Base editing and prime editing each have their own strengths and weaknesses. Whether a scientist should use base or prime editing depends on numerous factors such as the specific sequence being edited, its unique sequence context, whether the edit will be made inside an animal or patient, and the specific goals of the scientist. </p>
<p><strong>How can gene editing treat disease?</strong></p>
<p>The words “bean” and “been” differ by only a single letter, yet they have completely different meanings. In a cellular context, a single-letter misspelling in a specific position in a person’s DNA – for example, from a C to a T – can mean the difference between a healthy individual and an individual with progeria, a rare genetic disease that causes children to age rapidly. Base editing has the potential to correct these small but critical DNA misspellings to reverse or cure disease.</p>
<p><a href="https://doi.org/10.1038/s41586-020-03086-7">In a 2021 study</a> that our lab conducted in collaboration with scientists at the National Institutes of Health and Vanderbilt University, we used base editing to reverse progeria in mice and more than doubled their life span. In the same year, we used base editing to convert a diseased form of the hemoglobin gene <em>HBB</em> to a benign variant to <a href="https://doi.org/10.1038/s41586-021-03609-w">treat sickle-cell disease in mice</a>. </p>
<p>Base editing has also been successfully used in humans. After treatments of chemotherapy and a bone marrow transplant failed to treat 13-year-old <a href="https://www.bbc.com/news/health-63859184">Alyssa’s</a> pediatric leukemia, she enrolled in a <a href="https://www.isrctn.com/ISRCTN15323014">clinical trial</a> led by <a href="https://www.waseemqasim.com/">Waseem Qasim’s team</a> at the University of College London. The base-edited T-cells cleared Alyssa’s cancer and she remains in complete remission seven months later. </p>
<p><strong>What implications does prime editing have for the study and treatment of genetic disease and human health?</strong></p>
<p>Much like base editing, <a href="https://doi.org/10.1016/j.tcb.2020.01.004">prime editing</a> has tremendous implications for studying and treating genetic diseases. Because of its unique ability to make virtually any localized change in DNA at a target sequence, prime editing has the potential to correct a much larger number of mutations that are known to cause genetic diseases than was previously possible. Before prime editors can be used routinely to treat genetic diseases, however, they must be tested for their safety and efficacy in patients, and for their compatibility with different delivery platforms.</p>
<p>Additionally, the therapeutic application of any genome editing technology requires a clear understanding of the relationship between the genetic mutation and the resulting disease to ensure that the benefits outweigh the risks. </p>
<p><strong>What recent or ongoing development are you most excited about in your field?</strong></p>
<p>I am excited that many labs, including <a href="https://www.liugroup.us/">my own</a>, are <a href="https://doi.org/10.1126/science.aax9181">developing methods</a> <a href="https://doi.org/10.1038/s41587-021-01133-w">to precisely</a> <a href="https://doi.org/10.1038/s41587-021-01133-w">install</a> entire healthy genes into specific positions in the human genome. This could expand the potential therapeutic reach of gene editing. </p>
<p>I’m also excited about <a href="https://doi.org/10.1038/s41392-019-0089-y">ongoing efforts</a> to develop delivery technologies that can safely and efficiently deliver genome editing agents into target cells in animals and human patients. Genome editing agents are unable to easily enter cells because of their large size, unlike <a href="https://www.cancer.gov/publications/dictionaries/cancer-terms/def/small-molecule-drug">small-molecule drugs</a> like ibuprofen and aspirin which can easily enter cells due to their low molecular weight. As a result, scientists have to use creative ways to deliver genome editors to their targets — a critical step if we hope to broaden the scope of therapeutic gene editing.</p>
<p>To this end, we recently developed <a href="https://doi.org/10.1016/j.cell.2021.12.021">engineered viruslike particles</a>, which are capable of delivering base editors and prime editors into specific tissues in living organisms. As the field continues to develop and improve delivery methods, the promise of therapeutic genome editing will continue to include more patient communities.</p>
<p><strong>What ethical aspects of this technology have you and other researchers considered?</strong></p>
<p>There are several ethical issues surrounding the technology that researchers in the field <a href="https://www.nature.com/articles/d41586-019-00726-5">have considered</a>, including the challenges of <a href="https://doi.org/10.1038/s41587-021-01191-0">achieving equitable access</a> to genome editing technologies, the <a href="https://doi.org/10.1089/crispr.2021.0053">potential for increased stigmatization</a> of marginalized individuals and the <a href="https://doi.org/10.1007/s13238-017-0477-4">potential for misuse</a>. In cases where the technology is used with good intent, such as to treat disease and alleviate suffering, questions of <a href="https://doi.org/10.1016/j.ymthe.2016.12.012">patient accessibility</a> become paramount.</p>
<p>No fundamental technology is inherently good or bad, and the ability to edit our genomes is no exception. My hope continues to be that we collectively and thoughtfully choose to use these powerful technologies for the betterment of as many people as possible.</p><img src="https://counter.theconversation.com/content/200803/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>DRL is a co-founder and consultant for Beam Therapeutics, Prime Medicine, Pairwise Plants, Exo Therapeutics, Chroma Medicine, Resonance Medicine, and Nvelop Therapeutics. He owns founders’ equity in these companies, receives consultancies from them, and serves on their scientific advisory boards. He also serves as a scientific advisory board member and equity owner of Tevard Biosciences and Insitro. DRL may receive honoraria and travel reimbursements for some speaking engagements. He is a co-inventor on patents related to his research, as listed on his CV at <a href="http://liugroup.us">http://liugroup.us</a>. Some of these patents have been licensed to companies including those listed above. Potential conflicts of interest between his academic activities and his activities with other entities including the companies above are actively disclosed and managed in accordance with the conflict of interest policies of the Broad Institute, Harvard University, and HHMI.
The policies are available at:
<a href="https://www.broadinstitute.org/administration/conflict-interest-policy">https://www.broadinstitute.org/administration/conflict-interest-policy</a>
<a href="https://vpr.harvard.edu/pages/financial-conflict-interest-policy">https://vpr.harvard.edu/pages/financial-conflict-interest-policy</a>
<a href="https://www.hhmi.org/about/policies">https://www.hhmi.org/about/policies</a></span></em></p>Chemist David Liu explains how gene editing is paving the way to treating and even curing certain genetic diseases.David Liu, Professor of the Natural Sciences at Harvard University, Harvard UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/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/2002102023-02-22T12:54:03Z2023-02-22T12:54:03ZHow frontotemporal dementia, the syndrome affecting Wendy Williams, changes the brain – research is untangling its genetic causes<figure><img src="https://images.theconversation.com/files/511473/original/file-20230221-16-3xvr3l.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1732%2C1732&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Some of the same genetic mutations can lead to FTD, ALS or symptoms of both.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/brain-lp-pr-royalty-free-illustration/1164761753">antoniokhr/iStock via Getty Images Plus</a></span></figcaption></figure><p>Around <a href="https://www.who.int/news-room/fact-sheets/detail/dementia">55 million people worldwide</a> suffer from dementia such as Alzheimer’s disease. On Feb. 22, 2024, it was revealed that former talk show host <a href="https://www.npr.org/2024/02/22/1233172648/wendy-williams-aphasia-frontotemporal-dementia-diagnosis">Wendy Williams</a> had been diagnosed with <a href="https://www.theaftd.org/what-is-ftd/disease-overview/">frontotemporal dementia, or FTD</a>, a rare type of dementia that typically affects people <a href="https://www.alzheimers.gov/alzheimers-dementias/frontotemporal-dementia">ages 45 to 64</a>. <a href="https://apnews.com/article/what-is-frontotemporal-dementia-bruce-willis-fbfdbfca4793bb65ef3f38f31e31bd68">Bruce Willis</a> is another celebrity who was diagnosed with the syndrome, according to his family. In contrast to Alzheimer’s, in which the major initial symptom is memory loss, FTD typically involves changes in behavior.</p>
<p>The <a href="https://www.nia.nih.gov/health/what-are-frontotemporal-disorders">initial symptoms of FTD</a> may include changes in personality, behavior and language production. For instance, some FTD patients exhibit inappropriate social behavior, impulsivity and loss of empathy. Others struggle to find words and to express themselves. This insidious disease can be especially hard for families and loved ones to deal with. There is no cure for FTD, and there are no effective treatments.</p>
<p><a href="https://www.theaftd.org/genetics-of-ftd/">Up to 40% of FTD cases</a> have some family history, which means a genetic cause may run in the family. Since researchers identified the first genetic mutations that cause FTD in 1998, <a href="https://doi.org/10.15252%2Fembj.201797568">more than a dozen genes</a> have been linked to the disease. These discoveries provide an entry point to determine the mechanisms that underlie the dysfunction of neurons and neural circuits in the brain and to use that knowledge to explore potential approaches to treatment.</p>
<p><a href="https://profiles.umassmed.edu/display/130139">I am a researcher</a> who studies the development of FTD and related disorders, including the motor neuron disease <a href="https://www.als.org">amyotrophic lateral sclerosis, or ALS</a>. ALS, also known as Lou Gehrig’s disease, results in progressive muscle weakness and death. Uncovering the similarities in pathology and genetics between FTD and ALS could lead to new ways to treat both diseases.</p>
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<figcaption><span class="caption">Wendy Williams’ care team announced her diagnosis of frontotemporal dementia on Feb. 22, 2024.</span></figcaption>
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<h2>Genetic causes of FTD</h2>
<p>Genes contain the instructions cells use to make the proteins that carry out functions essential to life. Mutated genes can result in mutated proteins that lose their normal function or become toxic. </p>
<p>How mutated proteins contribute to FTD has been under intense investigation for decades. For instance, one of the key proteins in FTD, called <a href="https://doi.org/10.1016%2Fj.neuron.2011.04.009">tau</a>, helps stabilize certain structures in neurons and can form clumps in diseased brains. Another key protein, <a href="https://doi.org/10.1038%2Fnrn.2017.36">progranulin</a>, regulates cell growth and a part of the cell called the lysosome that breaks down cellular waste products.</p>
<p>Remarkably, the most common genetic mutation in FTD – in a gene called C9orf72 – <a href="https://doi.org/10.15252%2Fembj.201797568">also causes ALS</a>. In fact, apart from the mutations in genes that encode for tau and progranulin, most genetic mutations that cause FTD <a href="https://doi.org/10.15252%2Fembj.201797568">also cause ALS</a>. Another protein, <a href="https://doi.org/10.15252/embj.201797568">TDP-43</a>, forms clumps in the brains of over 95% of ALS cases and almost half of FTD cases. Thus, these disorders share close links in genetics and pathology.</p>
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<figcaption><span class="caption">Frontotemporal dementia typically affects people under 60.</span></figcaption>
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<h2>Modifier genes</h2>
<p>The same genetic mutation can cause FTD in one patient, ALS in another or symptoms of both FTD and ALS at the same time. Remarkably, some people who carry these genetic mutations may have no obvious symptoms for decades.</p>
<p>One reason the same mutation can cause both FTD and ALS is that, in addition to <a href="https://theconversation.com/als-is-only-50-genetic-identifying-dna-regions-affected-by-lifestyle-and-environmental-risk-factors-could-help-pinpoint-avenues-for-treatment-179169">lifestyle and environmental factors</a>, other genes may also influence whether mutated genes lead to disease. Identifying these <a href="https://doi.org/10.1016%2Fj.neuron.2020.08.022">modifier genes</a> in FTD, ALS and other neurodegenerative diseases could lead to new treatment approaches by boosting the activity of those that protect against disease or suppressing the activity of those that promote disease. </p>
<p>Modifier genes have long been a focus of research in <a href="https://www.umassmed.edu/fen-biaogaolab/">my laboratory</a> at the University of Massachusetts Chan Medical School. When my laboratory was still in San Francisco, we collaborated with neurologist <a href="https://profiles.ucsf.edu/bruce.miller">Bruce Miller</a> and generated the first stem cell lines from FTD patients with mutations in <a href="https://doi.org/10.1016%2Fj.celrep.2012.09.007">progranulin</a> and <a href="https://doi.org/10.1007%2Fs00401-013-1149-y">C9orf72</a>. These stem cells can be turned into neurons for researchers to study in a petri dish. My team also uses fruit flies to identify modifier genes and then test how they influence disease in neurons from patients with FTD or ALS.</p>
<p>For instance, in close collaboration with cell biologist <a href="https://www.stjude.org/directory/t/j-paul-taylor.html">J. Paul Taylor</a>, my laboratory was among the first to discover a small <a href="https://doi.org/10.1038%2Fnature14974">subset of modifier genes</a> that help transport molecules into or out of the nucleus of a neuron. We also <a href="https://doi.org/10.1016%2Fj.neuron.2016.09.015">discovered</a> <a href="https://doi.org/10.1073%2Fpnas.1901313116">modifier genes</a> that encode for some proteins that help repair damaged DNA. Targeting these modifier genes using <a href="https://doi.org/10.1089%2Fnat.2018.0725">gene-silencing techniques</a> developed by Nobel laureate <a href="https://www.nobelprize.org/prizes/medicine/2006/mello/facts/">Craig Mello</a> and other researchers at UMass Chan could offer potential treatments.</p>
<h2>Treating behavioral changes in FTD</h2>
<p>Because the brain is an extremely complex organ, it can be very difficult to understand what causes personality and behavioral changes in FTD patients. </p>
<p>Over the years, my team has used mice to study the causes of these changes. For instance, we found that the reduced social interaction we observed in mice engineered to have FTD is linked to <a href="https://doi.org/10.1038%2Fnm.3717">two different</a> <a href="https://doi.org/10.1038%2Fs41593-019-0397-0">disease proteins</a> in the same part of the brain, suggesting that this symptom may be caused by defects in the same neural circuit. These deficits could be reversed by injecting a molecule called <a href="https://doi.org/10.1038%2Fnm.3717">microRNA-124</a> into the prefrontal cortex, the part of the brain that controls social behaviors.</p>
<p>Moreover, with my longtime collaborator neuroscientist <a href="https://www.upstate.edu/psych/faculty.php?empID=yaow">Wei-Dong Yao</a>, our labs found that mice with FTD have <a href="https://doi.org/10.1038%2Fnm.3717">defects at</a> <a href="https://doi.org/10.1038%2Fs41593-019-0397-0">the synapses</a> in this part of the brain. Synapses are areas where neurons are in contact with each other and play an important role in transporting information in the nervous system. Recently, he found that <a href="https://doi.org/10.1016/j.neuron.2022.12.027">lack of empathy</a> in another mouse model of FTD could be reversed by increasing activity in the prefrontal cortex. </p>
<p>Further research to understand the molecular mechanisms and brain circuitry behind FTD offer hope that its devastating symptoms, including behavioral and personality changes, will be treatable in the future.</p>
<p><em>This is an updated version of an article originally published on Feb. 22, 2023.</em></p><img src="https://counter.theconversation.com/content/200210/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Fen-Biao Gao receives and has previously received funding from the NIH, The Muscular Dystrophy Association, The Association for FTD, Target ALS Foundation, The ALS Association, The Tau Consortium, The Consortium for Frontotemporal Dementia Research, The Ricico Fund, The Cellucci Fund, Merck, and Stealth BioTherapeutics.
He works for the NIH as a member of its CMND study section, for The Muscular Dystrophy Association as a member of its Research Advisory Council and for The Association for FTD as a member of its Scientific Review Panel. </span></em></p>FTD leads to changes in personality and behavior. Understanding its genetic and molecular causes could lead to new ways to treat neurodegenerative diseases.Fen-Biao Gao, Professor of RNA Therapeutics, Governor Paul Cellucci Chair in Neuroscience Research, Founding Director of Frontotempral Dementia Research Center, UMass Chan Medical SchoolLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1875152022-08-01T12:27:02Z2022-08-01T12:27:02ZHelping cells become better protein factories could improve gene therapies and other treatments – a new technique shows how<figure><img src="https://images.theconversation.com/files/476727/original/file-20220729-13650-l4tehb.jpg?ixlib=rb-1.1.0&rect=5%2C0%2C1991%2C1500&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Your genetic material instructs your cells to produce the proteins encoded in it.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/protein-synthesis-illustration-royalty-free-illustration/1296294290">Juan Gaertner/Science Photo Library via Getty Images</a></span></figcaption></figure><p>The cells in your body are <a href="https://www.ncbi.nlm.nih.gov/books/NBK26885/">not all the same</a>. Each of your organs has cells with very different functions. For example, liver cells are top-notch secretors, as their job requires them to make and export many of the proteins in your blood. By contrast, muscle cells are tasked with facilitating the contractions that allow you to move. </p>
<p>The fact that cells are so specialized has implications for <a href="https://medlineplus.gov/genetics/understanding/therapy/procedures/">gene therapy</a>, a way to treat genetic diseases by correcting the source of the error in a patient’s DNA. Health providers use a harmless <a href="https://patienteducation.asgct.org/gene-therapy-101/vectors-101">viral or bacterial vector</a> to carry a corrective gene into a patient’s cells, where the gene then directs the cell to produce the proteins necessary to treat the disease. Muscle cells are a common target because gene therapies <a href="https://medlineplus.gov/genetics/understanding/therapy/procedures/">injected into the muscle</a> are more accessible than introduction into the body by other routes. But muscle cells may not produce the desired protein as efficiently as needed if the job the gene instructs it to do is very different from the one it specializes in.</p>
<p>We are <a href="https://scholar.google.com/citations?user=SPyKrnIAAAAJ&hl=en">cell biologists</a> and <a href="https://scholar.google.com/citations?user=PL6N9eoAAAAJ&hl=en">biophysicists</a> who study how healthy proteins are produced and maintained in cells. This field is called <a href="https://doi.org/10.1093%2Fgerona%2Fgln071">protein homeostasis, also known as proteostasis</a>. Our <a href="https://dx.doi.org/10.1073/pnas.2206103119">recently published study</a> details a way to make muscle cells behave more like liver cells by changing protein regulation networks, enhancing their ability to respond to gene therapy and treat genetic diseases.</p>
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<figcaption><span class="caption">Gene therapy involves replacing a defective gene with a functioning one that can direct cells to produce missing or dysfunctional proteins.</span></figcaption>
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<h2>Boosting protein factories</h2>
<p>One disease for which gene therapy has great potential is <a href="http://doi.org/10.1056/NEJMra1910234">alpha-1 antitrypsin (AAT) deficiency</a>, a condition in which liver cells are unable to make adequate amounts of the protein AAT. It results in a breakdown of lung tissue that can cause <a href="https://www.uncoveralpha1.com/what-is-alpha-1">serious respiratory problems</a>, including the development of severe lung diseases such as chronic obstructive pulmonary disease (COPD) or emphysema. </p>
<p>Patients are usually treated by <a href="https://www.nhlbi.nih.gov/health/alpha-1-antitrypsin-deficiency">receiving AAT via infusion</a>. But this requires patients to either make regular trips to the hospital or keep expensive equipment at home for the rest of their lives. Replacing the faulty gene that caused their AAT shortage in the first place could be a boon for patients. Current gene therapies inject the AAT-producing gene into muscle. One of our colleagues, <a href="https://scholar.google.com/citations?user=Sd6B6-UAAAAJ&hl=en">Terence Flotte</a>, developed a way to use a harmless version of an adeno-associated virus as a vehicle to deliver AAT gene therapies into the body via injection, allowing for <a href="https://doi.org/10.1016/j.ymthe.2017.03.029">sustained release of the protein</a> over several years.</p>
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<a href="https://images.theconversation.com/files/476729/original/file-20220729-13356-h2dp31.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Microscopy image of panlobular emphysema" src="https://images.theconversation.com/files/476729/original/file-20220729-13356-h2dp31.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/476729/original/file-20220729-13356-h2dp31.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=404&fit=crop&dpr=1 600w, https://images.theconversation.com/files/476729/original/file-20220729-13356-h2dp31.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=404&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/476729/original/file-20220729-13356-h2dp31.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=404&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/476729/original/file-20220729-13356-h2dp31.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=507&fit=crop&dpr=1 754w, https://images.theconversation.com/files/476729/original/file-20220729-13356-h2dp31.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=507&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/476729/original/file-20220729-13356-h2dp31.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=507&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Lung damage from alpha-1 antitrypsin deficiency can lead to emphysema.</span>
<span class="attribution"><a class="source" href="https://flic.kr/p/8TqvpQ">Atlas of Pulmonary Pathology/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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</figure>
<p>But muscle cells aren’t very good at producing the AAT proteins the gene instructs them to make. Flotte and his team found that AAT levels one to five years after gene therapy were <a href="https://doi.org/10.1016/j.ymthe.2017.03.029">only 2% to 2.5%</a> of the optimal concentration for therapeutic effect.</p>
<p>We wanted to find a way to turn muscle cells into better protein factories, like liver cells. We tested a number of different molecules on mice muscle cells to determine if they would boost AAT secretion. We found that adding a molecule called <a href="https://doi.org/10.1074/jbc.M112.404707">suberoylanilide hydroxamic acid, or SAHA</a>, helps muscle cells make AAT at a production level more like that of liver cells. It works because SAHA is a <a href="https://doi.org/10.7554%2FeLife.15550">proteostasis regulator</a> with the ability to boost the cell’s protein output.</p>
<p>Down the road, we believe that adding SAHA or similar proteostasis regulators to gene therapies could help increase the effectiveness of these treatments for many genetic diseases.</p>
<h2>Beyond gene therapy</h2>
<p>Our findings have implications beyond just gene therapies. The effectiveness of <a href="https://doi.org/10.1038/s41573-021-00283-5">mRNA vaccines</a>, for example, is also affected by how well each cell produces a particular type of protein. Because most mRNA vaccines are given through an injection to the muscle, they may also face the same limitations as gene therapies and produce a lower-than-desirable immune response. Increasing the protein production of muscle cells could potentially improve vaccine immunity.</p>
<p>Additionally, many drugs created by the biotech industry called <a href="https://www.fda.gov/about-fda/center-biologics-evaluation-and-research-cber/what-are-biologics-questions-and-answers">biologics</a> that are derived from natural sources rely heavily on a given cell’s <a href="https://doi.org/10.3389/fbioe.2019.00420">protein production capabilities</a>. But many of these drugs use <a href="https://weekly.biotechprimer.com/biomanufacturing-how-biologics-are-made/">cells that aren’t specialized to make large amounts of protein</a>. Adding a protein homeostasis enhancer to the cell could optimize protein yield and increase the effectiveness of the drug.</p>
<p>Protein homeostasis is a burgeoning field that goes beyond drug development. Many <a href="https://doi.org/10.1038/s41580-019-0101-y">neurodegenerative diseases</a> like Alzheimer’s and Parkinson’s are linked to abnormal protein regulation. The deterioration of a cell’s ability to manage protein production and use over time may contribute to age-related diseases. Further research on ways to improve the cellular machinery behind protein homeostasis could help delay aging and open many new doors for treating a wide range of diseases.</p><img src="https://counter.theconversation.com/content/187515/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Daniel N. Hebert receives funding from Alpha One Foundation and NIH/NIGMS. </span></em></p><p class="fine-print"><em><span>Lila Gierasch receives funding from NIH/NIGMS and the Alpha1 Foundation.</span></em></p>Gene therapies and vaccines are often injected into muscle cells that are inefficient at producing desired proteins. Making them work more like liver cells could lead to better treatment outcomes.Daniel N. Hebert, Professor of Biochemistry and Molecular Biology, UMass AmherstLila Gierasch, Distinguished Professor of Biochemistry and Molecular Biology, UMass AmherstLicensed 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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<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>
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<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/1572102021-04-15T12:39:17Z2021-04-15T12:39:17ZScientists are on a path to sequencing 1 million human genomes and use big data to unlock genetic secrets<figure><img src="https://images.theconversation.com/files/395117/original/file-20210414-20-1od1b13.png?ixlib=rb-1.1.0&rect=32%2C64%2C3047%2C2349&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A complete human genome, seen here in pairs of chromosomes, offers a wealth of information, but it is hard connect genetics to traits or disease.</span> <span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:UCSC_human_chromosome_colours.png#/media/File:UCSC_human_chromosome_colours.png">HYanWong/Wikimedia Comons</a></span></figcaption></figure><p>The first draft of the human genome was <a href="https://www.washingtonpost.com/archive/politics/2000/06/27/teams-finish-mapping-human-dna/3af9bfcf-e7b6-4ac1-bcdb-f4fc117c19bd/">published 20 years ago</a> in <a href="https://www.genome.gov/25520483/online-education-kit-2001-first-draft-of-the-human-genome-sequence-released">2001</a>, took nearly three years and cost <a href="https://www.genome.gov/about-genomics/fact-sheets/Sequencing-Human-Genome-cost">between US$500 million and $1 billion</a>. The <a href="https://www.genome.gov/human-genome-project">Human Genome Project</a> has allowed scientists to read, almost end to end, the 3 billion pairs of DNA bases – or “letters” – that biologically define a human being. </p>
<p>That project has allowed a new generation of <a href="https://scholar.google.com/citations?user=Yy8gde8AAAAJ&hl=en&oi=ao">researchers like me</a>, currently a postdoctoral fellow at the National Cancer Institute, to identify <a href="https://doi.org/10.1038/s41586-020-2099-x">novel targets for cancer treatments</a>, engineer <a href="https://doi.org/10.1038/s41590-019-0416-z">mice with human immune systems</a> and even build a <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&lastVirtModeType=default&lastVirtModeExtraState=&virtModeType=default&virtMode=0&nonVirtPosition=&position=chr14%3A95086244%2D95158010&hgsid=1066518897_QJL7hsBNGEhTnw6DgqcZaMG4YFB2">webpage where anyone can navigate the entire human genome</a> with the same ease with which you use Google Maps.</p>
<p>The first complete genome was generated from a handful of anonymous donors to try to produce a reference genome that represented more than just one single individual. But this fell far short of encompassing <a href="https://doi.org/10.1038/nature18964">the wide diversity of human populations in the world</a>. No two people are the same and no two genomes are the same, either. If researchers wanted to understand humanity in all its diversity, it would take sequencing thousands or millions of complete genomes. Now, a project like that is underway. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/395378/original/file-20210415-18-fmgye7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A diverse group of people." src="https://images.theconversation.com/files/395378/original/file-20210415-18-fmgye7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/395378/original/file-20210415-18-fmgye7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=493&fit=crop&dpr=1 600w, https://images.theconversation.com/files/395378/original/file-20210415-18-fmgye7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=493&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/395378/original/file-20210415-18-fmgye7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=493&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/395378/original/file-20210415-18-fmgye7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=619&fit=crop&dpr=1 754w, https://images.theconversation.com/files/395378/original/file-20210415-18-fmgye7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=619&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/395378/original/file-20210415-18-fmgye7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=619&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 is a huge amount of genetic variation between people around the globe.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/group-portrait-of-people-smiling-royalty-free-image/560447233?adppopup=true">Flashpop/DigitalVision via Getty Images</a></span>
</figcaption>
</figure>
<h2>Understanding genetic diversity</h2>
<p>The wealth of genetic variation among people is what makes each person unique. But genetic changes also cause many disorders and make some groups of people more susceptible to certain diseases than others.</p>
<p>Around the time of the Human Genome Project, researchers were also sequencing the complete genomes of organisms such as <a href="https://doi.org/10.1038/nature01262">mice</a>, <a href="https://doi.org/10.1126/science.287.5461.2185">fruit flies</a>, <a href="https://doi.org/10.1126/science.274.5287.546">yeasts</a> and <a href="https://doi.org/10.1038/35048692">some plants</a>. The huge effort made to generate these first genomes led to a revolution in the technology required to read genomes. Thanks to these advances, instead of taking years and costing hundreds of millions of dollars to sequence a whole human genome, it now takes <a href="https://www.genome.gov/about-genomics/fact-sheets/Sequencing-Human-Genome-cost">a few days and costs merely a thousand dollars</a>. Genome sequencing is very different from genotyping services like 23 and Me or Ancestry, which look at only a tiny fraction of locations in a person’s genome.</p>
<p>Advances in technology have allowed scientists to sequence the complete genomes of thousands of individuals from around the world. Initiatives such as the <a href="https://gnomad.broadinstitute.org/">Genome Aggregation Consortia</a> are currently making efforts to collect and organize this scattered data. So far, that group has been able to gather nearly <a href="https://doi.org/10.1038/s41586-020-03174-8">150,000 genomes</a> that show an incredible amount of human genetic diversity. Within that set, researchers have found more than 241 million differences in people’s genomes, <a href="https://doi.org/10.1038/nature19057">with an average of one variant for every eight base pairs</a>.</p>
<p>Most of these variations are very rare and will have no effect on a person. However, hidden among them are variants with important physiological and medical consequences. For example, certain variants in the BRCA1 gene predispose some groups of woman, like Ashkenazi Jews, to <a href="https://doi.org/10.1038/s41586-018-0461-z">ovarian and breast cancer</a>. Other variants in that gene lead some <a href="https://doi.org/10.1038/s41467-018-06616-0">Nigerian women to experience higher-than-normal mortality</a> from breast cancer. </p>
<p>The best way researchers can identify these types of population-level variants is through <a href="https://www.ebi.ac.uk/gwas/">genomewide association studies</a> that compare the genomes of large groups of people with a control group. But diseases are complicated. An individual’s lifestyle, symptoms and time of onset can vary greatly, and the effect of genetics on many diseases is hard to distinguish. The predictive power of current genomic research is too low to tease out many of these effects because <a href="https://doi.org/10.1038/s41588-018-0313-7">there isn’t enough genomic data</a>.</p>
<p>Understanding the genetics of complex diseases, especially those related to the genetic differences among ethnic groups, is essentially a big data problem. And researchers need more data.</p>
<h2>1,000,000 genomes</h2>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/395116/original/file-20210414-16-rrcqz1.gif?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="The double helix DNA structure." src="https://images.theconversation.com/files/395116/original/file-20210414-16-rrcqz1.gif?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/395116/original/file-20210414-16-rrcqz1.gif?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=1038&fit=crop&dpr=1 600w, https://images.theconversation.com/files/395116/original/file-20210414-16-rrcqz1.gif?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=1038&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/395116/original/file-20210414-16-rrcqz1.gif?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=1038&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/395116/original/file-20210414-16-rrcqz1.gif?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1304&fit=crop&dpr=1 754w, https://images.theconversation.com/files/395116/original/file-20210414-16-rrcqz1.gif?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1304&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/395116/original/file-20210414-16-rrcqz1.gif?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1304&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 link between genetics and disease is nuanced, but the more genomes you can study, the easier it is to find those links.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:DNA_animation.gif#/media/File:DNA_animation.gif">brian0918/Wikimedia Commons</a></span>
</figcaption>
</figure>
<p>To address the need for more data, the National Institutes of Health has started a program called <a href="https://allofus.nih.gov/">All of Us</a>. The project aims to collect genetic information, medical records and health habits from surveys and wearables of more than a million people in the U.S. over the course of 10 years. It also has a goal of gathering more data from underrepresented minority groups to facilitate the study of health disparities. The <a href="https://www.fda.gov/regulatory-information/selected-amendments-fdc-act/21st-century-cures-act">All of Us project</a> opened to public enrollment in 2018, and more than 270,000 people have contributed samples since. The project is continuing to recruit participants from all 50 states. Participating in this effort are many academic laboratories and private companies.</p>
<p>This effort could benefit scientists from a wide range of fields. For instance, a neuroscientist could look for genetic variations associated with depression while taking into account exercise levels. An oncologist could search for variants that correlate with reduced risk of skin cancer while exploring the influence of ethnic background.</p>
<p>A million genomes and the accompanying health and lifestyle information will provide an extraordinary wealth of data that should allow researchers to discover the effects of genetic variation on diseases, not only for individuals, but also within different groups of people.</p>
<p>[<em>Understand new developments in science, health and technology, each week.</em> <a href="https://theconversation.com/us/newsletters/science-editors-picks-71/?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=science-understand">Subscribe to The Conversation’s science newsletter</a>.]</p>
<h2>The dark matter of the human genome</h2>
<p>Another benefit of this project is that it will allow scientists to learn about parts of the human genome that are currently very hard to study. Most genetic research has been on the parts of the genome that encode for proteins. However, these represent only <a href="https://dx.doi.org/10.1038%2Fnrd.2018.93">1.5% of the human genome</a>.</p>
<p>My research focuses on RNA – a molecule that turns the messages encoded in a person’s DNA into proteins. However, RNAs that come from the 98.5% of the human genome that doesn’t make proteins have a myriad of functions by themselves. Some of these noncoding RNAs are involved in processes such as <a href="https://doi.org/10.1038/nature08975">how cancer spreads</a>, <a href="https://doi.org/10.1242/dev.146613">embryonic development</a> or <a href="https://doi.org/10.1038/35047580">controlling the X chromosome in females</a>. In particular, I study how genetic variations can influence the intricate folding that allows noncoding RNAs to do their jobs. Since the All of Us project includes all coding and noncoding parts of the genome, it is going to be by far the largest dataset relevant to my work and will hopefully shed light on these mysterious RNAs.</p>
<p>The first human genome sparked 20 years of incredible scientific progress. I think it is almost certain that a huge dataset of genomic variations will unlock clues about complex diseases. Thanks to large-scale population studies and big-data projects such as All of Us, researchers are paving the way to answering, in the next decade, how our individual genetics shape our health.</p>
<p><em>A photo in this story was updated to better represent our editorial guidelines.</em></p><img src="https://counter.theconversation.com/content/157210/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Xavier Bofill De Ros receives funding from the National Institutes of Health (NIH). He is affiliated with ECUSA, an association of Spanish scientists in the USA.</span></em></p>The first full human genome was sequenced 20 years ago. Now, a project is underway to sequence 1 million genomes to better understand the complex relationship between genetics, diversity and disease.Xavier Bofill De Ros, Research Fellow in RNA biology, National Institutes of HealthLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1536412021-02-01T18:58:20Z2021-02-01T18:58:20ZNew CRISPR technology could revolutionise gene therapy, offering new hope to people with genetic diseases<figure><img src="https://images.theconversation.com/files/381591/original/file-20210201-13-qr3zh4.jpg?ixlib=rb-1.1.0&rect=47%2C4%2C3147%2C1571&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>The day a muddled mob stormed the US Capitol building, a team of American researchers published a paper <a href="https://www.nature.com/articles/s41586-020-03086-7">in Nature</a> that signified a landmark in gene therapy.</p>
<p>The head of the US National Institutes of Health, Francis Collins had joined forces with Harvard University professor David Liu and others to tackle progeria, a genetic disorder that causes children to age rapidly. </p>
<p>The achievement, successfully tested in mice, was made possible by Liu’s invention of a second-generation CRISPR gene-editing technology called “base editing”. With this, researchers may eventually be able to correct lifelong genetic diseases, including <a href="https://www.webmd.com/children/progeria#1">progeria</a>, in humans.</p>
<h2>A rare but devastating disease</h2>
<p>Francis Collins, former leader of the Human Genome Project, had worked on progeria for many years before the breakthrough. </p>
<p>Children carrying the mutation for progeria have normal intelligence but show early signs of general ageing, including hair loss and hearing loss. By their teenage years they appear very old. Few live past the age of 13. </p>
<p>In 2003, Collins’s lab <a href="https://directorsblog.nih.gov/tag/progeria/">discovered</a> progeria is caused by a mutation (which you can think of as a “misspelling”) in a gene that encodes a protein called Lamin A. Lamin A has a structural role in the cell’s nucleus. </p>
<p>Many of us carry mutations in various genes. But as we typically have two copies of genes (one from our mother and one from our father), we tend to have at least one good copy and that’s usually enough.</p>
<p>But the progeria mutation in Lamin A is different. While there may be a good copy present, the mutant copy generates a poisonous product that messes things up, like a spanner in the works. This type of mutation is called a “dominant negative mutation”.</p>
<p>The solution, ideally, would be to specifically correct the mutant copy using <a href="https://theconversation.com/what-is-crispr-gene-editing-and-how-does-it-work-84591">CRISPR</a>. With this gene-editing tool, scientists can direct a pair of molecular “scissors” to any part of the genome (DNA). Unfortunately, first-generation CRISPR technologies — while good at cutting genes — do not have the level of surgical precision or efficiency needed to correct the Lamin A mutation. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/explainer-what-is-a-gene-12951">Explainer: what is a gene?</a>
</strong>
</em>
</p>
<hr>
<h2>Complications with mass cell editing</h2>
<p>CRISPR scissors are good at finding their target and cutting, but the reconstructive surgery that comes after is left to the cell — and isn’t guaranteed to happen in every cell. </p>
<p>In the lab, researchers can usually manage by just correcting a few cells before growing them in a petri dish for further research. </p>
<p>But in humans we need to accurately correct most, if not all, cells. It would be pointless to correct the progeria mutation in five cells in a patient’s finger, while leaving the rest of the body unrepaired.</p>
<p>This is where David Liu’s work on “base editors” is critical. Liu identified the limitations of CRISPR technology very early and began developing molecular machines that could do more than operate only as targeted molecular scissors. </p>
<p>He started with naturally occurring enzymes, which can change one type of chemical base of the genetic code into another; for example, enzymes that can convert an A (adenine) to a G (guanine), or a C (cytosine) to a T (thymine).</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/381581/original/file-20210201-23-o5yyqz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram showing basic DNA structure and chemical bases." src="https://images.theconversation.com/files/381581/original/file-20210201-23-o5yyqz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/381581/original/file-20210201-23-o5yyqz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/381581/original/file-20210201-23-o5yyqz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/381581/original/file-20210201-23-o5yyqz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/381581/original/file-20210201-23-o5yyqz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/381581/original/file-20210201-23-o5yyqz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/381581/original/file-20210201-23-o5yyqz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The double helix shape of DNA is supported by an alternating sugar-phsophate backbone (the sides). Attached to each sugar on the backbone is one of four chemical bases: adenine (A), thymine (T), guanine (G) and cytosine (C). The order of these bases is what determines an organism’s genetic code.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<p>Liu then modified the enzymes to make them more precise and fused them to CRISPR to create fusion proteins called “base editors”. Since CRISPR technology is good at reading DNA and finding a target, it can effectively deliver the editors to the gene that needs to be changed.</p>
<p>It’s important to highlight Liu deliberately developed base editors so that they change letters, but no longer sever DNA like CRISPR scissors. This is crucial, as cutting DNA increases the risk of larger chromosomal deletions, which can potentially damage cells.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/the-resilience-project-finding-those-rare-people-with-genetic-disease-mutations-who-are-healthy-57800">The Resilience Project: finding those rare people with genetic disease mutations who are healthy</a>
</strong>
</em>
</p>
<hr>
<h2>The differences of mice and men</h2>
<p>Collins, Liu and their colleagues knew they would have to get base editors into all (or at least <em>most</em>) of the cells of a mouse with progeria to cure it. For this, they relied on using hollowed-out viruses as delivery vectors. </p>
<p>They used a vector based on the Adeno Associated Virus, or AAV. As students, we joked AAV stood for “almost a virus”, as it’s one of the smallest viruses and doesn’t cause any known disease. </p>
<p>Collins and Liu packaged the AAV virus particles with genes encoding the relevant base-editing enzyme and delivered them into the mice. The treated mice essentially avoided the disease and became indistinguishable from healthy mice.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/GO306dK8m8c?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">In this video, Collins and Lui discuss their work involving treating progeria in mice.</span></figcaption>
</figure>
<p>But, of course, this all happened in mice — and humans are bigger. We don’t know how difficult it will be to upscale this gene-editing machinery to work reliably in humans. But in any case, Collins and Liu have taken an inspiring first step by showing it’s possible in mice. </p>
<p>Base-editing CRISPR tools are a dream come true for experts committed to gene therapy and for families afflicted by conditions such as progeria. Work on this front is just beginning. But in these dark pandemic times, it provides much-needed new hope.</p><img src="https://counter.theconversation.com/content/153641/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Merlin Crossley works for UNSW as Deputy Vice-Chancellor Academic and Student Experience, and a Professor of Molecular Biology. He holds or has held Australian Research Council and National Health and Medical Research Council grants, and collaborates with biotechnology companies, such as CSL and various international labs doing CRISPR-gene editing. He is on the Board of The Conversation, and Chair of the Editorial Board, Chair of UNSW Press, Deputy Director of the Australian Science Media Centre, and is an Honorary Associate of the Australian Museum. </span></em></p>Using ‘base editing’, researchers have cured progeria in mice. This genetic syndrome causes premature ageing in humans – those with the disease usually don’t live past the age of 13.Merlin Crossley, Deputy Vice-Chancellor Academic and Professor of Molecular Biology, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/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>
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</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>
<p>[<em>Deep knowledge, daily.</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=deepknowledge">Sign up for The Conversation’s newsletter</a>.]</p>
<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.tag:theconversation.com,2011:article/1265912019-11-11T03:23:04Z2019-11-11T03:23:04Z3-parent IVF could prevent illness in many children (but it’s really more like 2.002-parent IVF)<figure><img src="https://images.theconversation.com/files/300804/original/file-20191108-10961-1saxnlu.jpg?ixlib=rb-1.1.0&rect=8%2C8%2C5742%2C3819&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Australians can now have their say on the issues around mitochondrial donation.</span> <span class="attribution"><span class="source">From shutterstock.com</span></span></figcaption></figure><p>Mitochondrial donation is an assisted reproductive technology sometimes described as “three-parent IVF”. It’s designed for women at high risk of passing on faulty mitochondrial DNA and having a child with severe mitochondrial disease. </p>
<p>Mitochondrial diseases comprise <a href="https://www.sciencedirect.com/science/article/pii/S014067361830727X?via%3Dihub">at least 300 different genetic conditions</a> which affect the energy-producing structures within human cells, impacting organ function.</p>
<p>Mitochondrial donation involves combining the 20,000 or so unique nuclear genes from the mother with the same number from the father – but replacing the mother’s 37 unique mitochondrial DNA genes with mitochondria from a donor egg. </p>
<p>In terms of genetic contribution (physical and personality traits), it would be more accurate to call mitochondrial donation “2.002-parent IVF”.</p>
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Read more:
<a href="https://theconversation.com/meet-mama-papa-and-mama-how-three-parent-ivf-works-15725">Meet mama, papa and mama: how three-parent IVF works</a>
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<p>Mitochondrial donation was legalised <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31868-3/fulltext">in the UK</a> in 2015. Now, Australia is considering introducing it.</p>
<p>Couples would be able to access the procedure if the mother has a family history of mitochondrial DNA disease, which may apply to <a href="https://www.nejm.org/doi/10.1056/NEJMc1500960?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dwww.ncbi.nlm.nih.gov">about 60 births</a> in Australia each year. </p>
<h2>Mitochondrial disease</h2>
<p>Mitochondria are small structures within our cells that regulate many aspects of metabolism. In particular, they convert sugars, fats and proteins into a form of energy our cells can use.</p>
<p>At least <a href="https://academic.oup.com/brain/article/126/8/1905/307996">one in 5,000 babies</a> will be affected by a severe mitochondrial disease during their lifetime. Problems in mitochondrial energy generation can present at any age and affect any organ system, alone or in combination.</p>
<p><a href="https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004426.pub3/full">We don’t have effective therapies</a> so, tragically, most affected children die before age five from respiratory failure, heart failure, liver failure or other causes.</p>
<p>More than half of patients don’t develop symptoms until adulthood. But they can suffer debilitating symptoms such as muscle weakness, diabetes, deafness, blindness, strokes, seizures, heart failure, kidney disease and <a href="https://www.nature.com/articles/nrdp201680">early death</a>.</p>
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Read more:
<a href="https://theconversation.com/viewpoints-the-promise-and-perils-of-three-parent-ivf-18402">Viewpoints: the promise and perils of three-parent IVF</a>
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<p>In about half of patients with mitochondrial disorders, the cause is a problem in one of the 20,000 nuclear genes we inherit from each parent. This is the case with other inherited diseases such as cystic fibrosis and thalassaemia. </p>
<p>In the other half it’s due to a problem in one of the 37 genes in the circular chromosome of mitochondrial DNA that lies outside the nucleus and is <a href="https://www.nature.com/articles/nrdp201680">inherited only from the mother’s mitochondria</a>. This is where mitochondrial donation can help.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/300805/original/file-20191108-10901-1dfdhx9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/300805/original/file-20191108-10901-1dfdhx9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/300805/original/file-20191108-10901-1dfdhx9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/300805/original/file-20191108-10901-1dfdhx9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/300805/original/file-20191108-10901-1dfdhx9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/300805/original/file-20191108-10901-1dfdhx9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/300805/original/file-20191108-10901-1dfdhx9.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">Mitochondria play an important role in regulating our metabolism.</span>
<span class="attribution"><span class="source">From shutterstock.com</span></span>
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</figure>
<p>While couples with a family history of conditions like muscular dystrophy or cystic fibrosis can use IVF technologies to have a child who will not be affected, these options are generally <a href="https://www.nature.com/articles/nbt.3997">unreliable for the prevention of mitochondrial DNA disease</a>. </p>
<p>This procedure would offer Australian couples with a family history of mitochondrial DNA disease access to a reproductive technology to facilitate conception of a healthy child genetically related to both parents.</p>
<h2>Safety and effectiveness</h2>
<p>Mitochondrial donation can be performed <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5890307/">either prior to or shortly after</a> fertilisation. In both cases, <a href="https://academic.oup.com/humrep/article/22/4/905/695880">this is before</a> the fertilized egg becomes an embryo.</p>
<p>However, a small number of maternal mitochondria are carried over, leaving the potential for <a href="https://www.nature.com/articles/nature18303">reversion to mutant mitochondrial DNA</a>. </p>
<p>It’s also possible the donor mitochondrial DNA will be incompatible with the parents’ nuclear genes, potentially causing disease. </p>
<p>Girls born following mitochondrial donation will pass on the donor mitochondrial DNA to any descendants. If any mutant mitochondrial DNA was carried over, it could potentially cause disease in her descendants. </p>
<p>For this reason a review in the United States recommended the procedure should be restricted to implanting <a href="http://www.nationalacademies.org/hmd/Reports/2016/Mitochondrial-Replacement-Techniques.aspx">male embryos only</a>.</p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/explainer-what-are-mitochondria-and-how-did-we-come-to-have-them-83106">Explainer: what are mitochondria and how did we come to have them?</a>
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<p>A number of scientists have suggested the proposed safety issues may be less relevant to clinical practice because they were based on, for example, <a href="https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004315">inbred mouse models</a> or <a href="https://www.nature.com/articles/nbt.3997">human embryonic stem cells</a> cultured in the lab.</p>
<p>Some reassurance may also be found in studies describing <a href="https://www.nature.com/articles/nature08368">macaque monkeys</a> born following mitochondrial donation. Meanwhile, human studies have reported apparently healthy children being <a href="https://www.clinicalkey.com.au/#!/content/playContent/1-s2.0-S147264831730041X?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS147264831730041X%3Fshowall%3Dtrue&referrer=https:%2F%2Fwww.ncbi.nlm.nih.gov%2F">born following mitochondrial donation</a> or what’s called <a href="https://www.clinicalkey.com.au/#!/content/playContent/1-s2.0-S1472648316305569?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1472648316305569%3Fshowall%3Dtrue&referrer=https:%2F%2Fwww.ncbi.nlm.nih.gov%2F">ooplasmic transfer</a> of a small proportion of mitochondria from a donor egg.</p>
<p>But those human studies avoided regulatory scrutiny and are limited by poor scientific design, while the macaque studies have not been followed through to adulthood yet. So some uncertainty remains about the safety and effectiveness of mitochondrial donation. </p>
<h2>Lessons from the UK</h2>
<p>The approval process in the UK included four separate scientific reviews. A <a href="https://www.nature.com/articles/nbt.3997">panel of embryologists and geneticists</a> considered data on human embryos, mice and monkeys that had undergone mitochondrial donation. They concluded the likely risks were low and it was safe <a href="https://www.hfea.gov.uk/media/2611/fourth_scientific_review_mitochondria_2016.pdf">to proceed cautiously</a>. </p>
<p>Mitochondrial donation in the UK is regulated to ensure the procedure is only used <a href="https://www.hfea.gov.uk/media/2611/fourth_scientific_review_mitochondria_2016.pdf">for prevention of severe mitochondrial DNA disease</a>, where the benefit to risk ratio is strong. It specifically excludes <a href="https://www.sciencedirect.com/science/article/pii/S2405661818300030?via%3Dihub">experimenting with the procedure to treat fertility</a>, which has been proposed by some IVF groups. The benefits versus risks in this case are less clear.</p>
<p>Many international experts on mitochondrial biology and disease supported the approach taken in the UK. We recommend Australia take a similar path.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/safety-in-numbers-how-three-parents-can-beat-genetic-diseases-2524">Safety in numbers: how three parents can beat genetic diseases</a>
</strong>
</em>
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<hr>
<p>Following <a href="https://www.aph.gov.au/Parliamentary_Business/Committees/Senate/Community_Affairs/MitochondrialDonation/Report">an Australian Senate Inquiry in 2018</a>, the <a href="https://www.aph.gov.au/Parliamentary_Business/Committees/Senate/Community_Affairs/MitochondrialDonation/Government_Response">government</a> tasked the National Health and Medical Research Council with providing expert input on legal, regulatory, scientific and ethical issues, as well as conducting public engagement. </p>
<p>Research suggests many Australians <a href="https://academic.oup.com/humrep/article/34/4/751/5377828">are likely to support this approach</a>, but further public input is important to guide legislative change. This includes consideration of ethical issues such as the rights and interests of the egg donor.</p>
<p>We encourage interested parties to engage with the <a href="https://www.nhmrc.gov.au/about-us/leadership-and-governance/committees/mitochondrial-donation">public consultation process</a> before submissions close on November 29.</p><img src="https://counter.theconversation.com/content/126591/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>David Thorburn receives funding from NHMRC, the US Department of Defense Congressionally Directed Medical Research Program and the Mito Foundation. He is a founding Director of the Mito Foundation and Chair of its Scientific & Medical Advisory Panel. </span></em></p><p class="fine-print"><em><span>John Christodoulou receives funding from NHMRC and the US DOD, as well as a number of disease specific organisations.
He is a founding Director of the Mito Foundation</span></em></p>Should Australia allow the creation of babies with DNA from more than two people? This reproductive technology could prevent babies being born with mitochondrial disease, so the simple answer is yes.David Thorburn, co-Group Leader, Brain & Mitochondrial Research, Murdoch Children's Research InstituteJohn Christodoulou, Director, Genetics Research Theme, Murdoch Children's Research InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1126002019-02-27T23:48:57Z2019-02-27T23:48:57ZIt’s time to rethink what the medical profession considers a ‘rare disease’<figure><img src="https://images.theconversation.com/files/261304/original/file-20190227-150698-1w2eprg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Rare diseases aren't, in fact, all that rare. Yet they continue to be brushed aside by most politicians. Why?
</span> <span class="attribution"><span class="source">Rawpixel/Unsplash</span></span></figcaption></figure><p><a href="https://www.rarediseaseday.org">International Rare Disease Day</a> is upon us. People around the world spend Feb. 28 raising awareness about the impact that diseases with low prevalence have on patients and their families.</p>
<p>The day also marks the passing of yet another year during which the government of Canada has failed to adopt a national rare disease strategy. This is particularly striking for a country with a robust public health-care system.</p>
<p>Everything about rare diseases is compelling; from their human impact to the genetic science that underpins most of them and the potential they hold for helping us gain a better understanding of more common diseases. </p>
<p>Despite this, rare diseases continue to be brushed aside by most politicians. Why is this? Could it finally be time for us to stop calling them “rare?”</p>
<h2>Not so rare</h2>
<p>Many countries have adopted definitions for rare diseases based on their prevalence within a population. These thresholds generally vary between <a href="https://www.sciencedirect.com/science/article/pii/S1098301515019798?via%3Dihub">countries and between patient populations</a>. </p>
<p>There is currently no international consensus about the number of rare diseases, but advocacy groups claim there are more than 7,000. Scientists estimate that roughly 80 per cent of these are genetic in origin, and the World Health Organization estimated in 2013 that <a href="https://www.who.int/medicines/areas/priority_medicines/MasterDocJune28_FINAL_Web.pdf?ua=1">one of every 15 people worldwide</a> are impacted by a rare disease — or approximately 400 million people in 2013.</p>
<h2>Wide-ranging benefits</h2>
<p>Unlike more common diseases, rare diseases generally do not benefit from economies of scale. Regardless, there is a great deal of interesting research being done into these diseases.</p>
<p>Breakthroughs in science such as the development of next-generation sequencing and genome editing tools like CRISPR-Cas9 are paving the way toward a greater understanding of the genetic tapestry underlying several rare diseases (for example, <a href="https://www.mdpi.com/2075-4426/8/4/38/htm">Duchenne Muscular Dystrophy</a> and NGLY1-deficiency). </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/261308/original/file-20190227-150705-1byhwon.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/261308/original/file-20190227-150705-1byhwon.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/261308/original/file-20190227-150705-1byhwon.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/261308/original/file-20190227-150705-1byhwon.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/261308/original/file-20190227-150705-1byhwon.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/261308/original/file-20190227-150705-1byhwon.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/261308/original/file-20190227-150705-1byhwon.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">Scientific breakthroughs are giving us a greater understanding of genetic diseases.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
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</figure>
<p>Recent studies even suggest that a better understanding of NGLY1-deficiency may help us to develop therapies for multiple myeloma and other <a href="https://pubs.acs.org/doi/10.1021/acscentsci.7b00224">devastating cancers</a> for which treatment options have been limited.</p>
<p>Research into undiagnosed genetic diseases is also starting <a href="https://www.nature.com/articles/s41436-019-0439-8">to benefit</a> from advancements in artificial intelligence and machine learning. </p>
<h2>‘Political won’t’</h2>
<p>The number of people with any particular rare disease in Canada is very low. Consequently, most disease-specific advocacy groups are relatively small in size. There are currently only two national advocacy groups in Canada, CORD (<a href="https://www.raredisorders.ca">Canadian Organization for Rare Disorders</a>) and RDF (<a href="https://rarediseasefoundation.org">Rare Disease Foundation</a>), that broadly advocate for all rare disease patient populations. </p>
<p>In contrast to the WHO, both the <a href="https://rarediseasefoundation.org/about/faq/">Rare Disease Foundation</a> and <a href="https://www.raredisorders.ca/our-work/">CORD</a> estimate that one in 12 Canadians have a rare disease. To date, however, no official definition for “rare disease” has been adopted by the government of Canada. </p>
<p>This could be because there has not been enough research into these numbers, but it could also be because some of our country’s leading experts disagree about the number of impacted individuals. <a href="https://theconversation.com/profiles/joel-lexchin-346457">Joel Lexchin</a>, a York University professor emeritus, testified before a House of Commons committee that the one in 12 number is <a href="https://lop.parl.ca/sites/Visit/default/en_CA">“unreliable.”</a> And Dr. Alex MacKenzie, a celebrated pediatric endocrinologist at the Children’s Hospital of Eastern Ontario, thinks the number is <a href="https://lop.parl.ca/sites/Visit/default/en_CA">“a bit inflated.”</a></p>
<p>Given the disagreement about even a definitional starting point, it’s unsurprising that <a href="http://www.health.gov.on.ca/en/common/ministry/publications/reports/rare_diseases_2017/rare_diseases_report_2017.pdf">no Canadian province or territory has implemented a comprehensive plan for rare diseases</a>, like the one put <a href="https://www.raredisorders.ca/content/uploads/CORD_Canada_RD_Strategy_22May15.pdf">forth by CORD</a> in 2015.</p>
<p>Ontario came close to putting a plan in place, but it lost steam after the 2018 election of Doug Ford as premier. The <a href="http://www.health.gov.on.ca/en/common/ministry/publications/reports/rare_diseases_2017/rare_diseases_report_2017.pdf">final report</a> of Ontario’s Working Group on Rare Disease (which includes 19 recommendations) now sits abandoned on a website under the dismissive header: <a href="http://www.health.gov.on.ca/en/news/bulletin/2017/hb_20171208.aspx">“This document was published under a previous government.”</a></p>
<h2>‘Kiss of death’</h2>
<p>Health Canada did publish a draft framework for rare disease drug approval on its website in 2012, but it was removed in 2017 in what CORD President Durhane Wong-Rieger described as the <a href="https://nationalpost.com/news/politics/health-canada-gives-kiss-of-death-to-planned-policy-for-rare-disease-drugs">“kiss of death for the orphan drug framework.”</a> An <a href="https://www.canada.ca/en/health-canada/services/licences-authorizations-registrations-drug-health-products/regulatory-approach-drugs-rare-diseases.html#1">“accelerated review pathway”</a> has since been adopted (although it is not dedicated specifically to rare diseases) in order to help facilitate the approval of drugs for rare disease. </p>
<p>Small patient groups can sometimes get the attention of policy-makers, but the victories are usually narrow in scope and in geographic reach. The <a href="http://www.health.gov.on.ca/en/news/bulletin/2016/hb_20160229.aspx">opening of a clinic</a> in Toronto for people living with <a href="http://www.ehlers-danlossyndromecanada.org/home.html">Ehlers-Danlos Syndrome</a> is a good example. </p>
<p>For some reason, rare diseases have generally not been treated as very important to Canadian policy-makers, despite our public health-care system and the federal government’s ability to use transfer payments to guide health-care delivery in the provinces.</p>
<p>Despite the fact that there is strength in numbers, it appears to be the case that rare diseases suffer from a branding problem in this country. Focusing on their low prevalence seems to give politicians, who like popular causes that can activate more voters, with an easy excuse to ignore the needs of these populations. </p>
<p>So is it time to abandon the word “rare” and try something new?</p><img src="https://counter.theconversation.com/content/112600/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ian Stedman is a rare disease patient who has Muckle Wells Syndrome. He is completing his PhD in public sector accountability law at Osgoode Hall Law School and receives funding as a Fellow in Artificial Intelligence Law and Ethics from the Centre for Computational Medicine and Toronto’s Hospital for Sick Children. Ian is a former member of the board of directors of the Canadian Organization for Rare Disorders.</span></em></p><p class="fine-print"><em><span>Ashwin Seetharaman holds a PhD in Molecular Genetics from the University of Toronto, Canada. Presently, as a postdoctoral research fellow at the University of Toronto. His research work is supported by funding from the Grace Science Foundation.</span></em></p><p class="fine-print"><em><span>Kristin Kantautas is PhD Candidate in the Department of Molecular Genetics at the University of Toronto. Her research is affiliated with the Grace Science Foundation. </span></em></p>Despite the fact that rare diseases aren’t actually so rare, it appears they suffer from a branding problem in Canada.Ian Stedman, Assistant Professor, Canadian Public Law & Governance, York University, CanadaAshwin Seetharaman, Postdoctoral Fellow, University of TorontoKristin Kantautas, PhD Candidate, Department of Molecular Genetics, University of TorontoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/870832017-11-16T19:10:53Z2017-11-16T19:10:53ZWhat prospective parents need to know about gene tests such as ‘prepair’<figure><img src="https://images.theconversation.com/files/194903/original/file-20171115-19789-17t9dhk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Couples who are carriers of genes for recessive diseases don't show any symptoms.</span> <span class="attribution"><a class="source" href="https://unsplash.com/photos/7tGqLzHcjZ8">Photo by Drew Hays on Unsplash</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>Researchers <a href="http://www.theage.com.au/victoria/most-wouldbe-parents-carrying-severe-genetic-disorders-are-unaware-20171102-gzd9vi.html">recently renewed calls</a> for all prospective parents to be offered testing for gene mutations that could be transferred to their child. This came after a study published in the journal <a href="https://www.nature.com/articles/gim2017134.epdf?referrer_access_token=vUswM29CZMNFQjzlclpL0NRgN0jAjWel9jnR3ZoTv0N5FKXZRBZzyrsg1x6BF7gWGcq5yVwW6B0Wzooc5EJ8jwvZGqeMfDai5LT6rCSx7IvdvZnxf-N9ynrk32fv6HJKo3FAyW2FI-QIvTbeQ4LGYR4_DuoStR47YWScTuzSRV0hsyl2RVimGDZfIS59fKHA7ZCVGkvi8y69kpbBRc13KXarZyJdI8loMbJS0V2j-MbP8JB2cuFZCfUU2hf6BXso9sBbqLbM2T6NhghxXvXV1Q%3D%3D&tracking_referrer=www.abc.net.au">Genetics in Medicine</a> found 88% of couples weren’t aware they were carrying mutations for three serious diseases: cystic fibrosis, spinal muscular atrophy and fragile X syndrome. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/194914/original/file-20171115-19823-xhiz6k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/194914/original/file-20171115-19823-xhiz6k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/194914/original/file-20171115-19823-xhiz6k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=900&fit=crop&dpr=1 600w, https://images.theconversation.com/files/194914/original/file-20171115-19823-xhiz6k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=900&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/194914/original/file-20171115-19823-xhiz6k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=900&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/194914/original/file-20171115-19823-xhiz6k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1130&fit=crop&dpr=1 754w, https://images.theconversation.com/files/194914/original/file-20171115-19823-xhiz6k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1130&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/194914/original/file-20171115-19823-xhiz6k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1130&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Diseases like cystic fibrosis have significant health consequences.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
</figcaption>
</figure>
<p>These three diseases have significant health consequences and are among the most common recessive diseases. This is where only one parent carries a copy of the gene mutation (both parents need a copy for the child to become sick) and shows no symptoms. A healthy individual who carries a single recessive mutation is called a carrier. </p>
<p>Recessive diseases cause many severe disorders in children, but most of us who are healthy carriers <a href="https://www.ncbi.nlm.nih.gov/pubmed/21228398?dopt=Citation">don’t know</a> how many or what mutations we carry. Pre-pregnancy or <a href="https://theconversation.com/explainer-what-is-pre-pregnancy-carrier-screening-and-should-potential-parents-consider-it-79184">preconception carrier screening</a> allows healthy couples to identify mutations they carry before they become pregnant. </p>
<p>So, what is the test used in the recent study, and should it be available to all prospective parents?</p>
<h2>What genetic tests are available?</h2>
<p>The recent study used the “<a href="https://www.vcgs.org.au/tests/prepair">prepair™ test</a>” to screen couples. It was conducted by the Victorian Clinical Genetics Service (VCGS), which provides the test to the public. The number of pregnancies affected with one of these three diseases (cystic fibrosis, spinal muscular atrophy and fragile X syndrome) during the course of the study was one in every 1,006 women. This figure is comparable to that of live births affected by <a href="http://www.who.int/genomics/public/geneticdiseases/en/index1.html">Down syndrome</a>. </p>
<p>Currently, <a href="https://www.alrc.gov.au/publications/10-genetic-testing/access-genetic-testing">government subsidies</a> for genetic testing and counselling are only available for couples once they have had a child with a suspected inherited disease or if there is a history for a particular disease in the extended family.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/why-should-we-offer-screening-for-down-syndrome-anyway-30351">Why should we offer screening for Down syndrome anyway?</a>
</strong>
</em>
</p>
<hr>
<p>Aside from the VCGS, there are at least five other providers in most Australian eastern states offering tests for different sets of recessive disorders. All five are consumer-pays tests. They range from A$350 to A$750, depending on the number of genes tested. </p>
<p>The largest gene panel tests for <a href="https://www.ivf.com.au/about-fertility/how-to-get-pregnant/preconception-screen">590 diseases</a> and costs the most, while <a href="https://www.sonicgenetics.com.au/tests/preconception-carrier-screening-panel-cf-sma-fragile-x/">others</a> only test for the same three recessive diseases VCGS offers. Another test screening for 175 recessive conditions is provided by <a href="https://www.counsyl.com/services/foresight/">Counsyl</a> through Australian clinicians.</p>
<h2>What can I expect from the prepair™ test?</h2>
<p>The VCGS prepair™ screens for specific mutations in the three genes causing the three diseases. Couples or individuals are considered at “increased risk” if they both carry a mutation for the same one of the three screened diseases. </p>
<p>The VCGS prepair™ genetic test is usually first offered to women before, or early, in their pregnancy (less than 12 weeks) by health professionals. These are usually GPs and obstetricians, as they are generally the first point of medical contact for soon-to-be-parents. Partners of carrier women are then offered testing.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/194908/original/file-20171115-19841-zws4gl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/194908/original/file-20171115-19841-zws4gl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/194908/original/file-20171115-19841-zws4gl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=857&fit=crop&dpr=1 600w, https://images.theconversation.com/files/194908/original/file-20171115-19841-zws4gl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=857&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/194908/original/file-20171115-19841-zws4gl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=857&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/194908/original/file-20171115-19841-zws4gl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1077&fit=crop&dpr=1 754w, https://images.theconversation.com/files/194908/original/file-20171115-19841-zws4gl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1077&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/194908/original/file-20171115-19841-zws4gl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1077&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">If each member of the couple carry the gene mutation for the same disease, their child has a 25% chance of the disorder.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
</figcaption>
</figure>
<p>All carriers are offered a genetic counselling appointment and an appointment with a paediatric sub-specialist who has expertise in the specific disease. Results are also discussed with the referring health professional. For individuals or couples not identified as carriers, the report is sent to the referring health professional and no further testing or follow-up is required. </p>
<p>If couples are carriers for mutations in the same gene, any of their children have a 25% chance of being affected by the disease. If couples do not carry any of the mutations the VCGS test screens for, they are considered at “low risk” of having an affected child. </p>
<p>But while the risk of having a child affected by a genetic mutation is greatly reduced, it is not eliminated. The main benefit of tests screening for hundreds of genes is that a couple can know their carrier status for many more recessive diseases. </p>
<h2>How can couples use the test to make decisions?</h2>
<p>Understanding what it means to be a carrier and a high-risk couple allows prospective parents to decide how they want to approach conception and pregnancy. At-risk couples and those with a previous history of recessive disease frequently want to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3149658/">avoid having an affected child</a>. Couples may then opt for in-vitro fertilisation (IVF) to select only healthy embryos (without two mutations) for implantation. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/rest-assured-ivf-babies-grow-into-healthy-adults-23432">Rest assured, IVF babies grow into healthy adults</a>
</strong>
</em>
</p>
<hr>
<p>Couples may also decide to fall pregnant naturally and then test the fetus, through a test called <a href="http://www.pregnancybirthbaby.org.au/chorionic-villus-sampling-cvs">chorionic villus sampling</a>, towards the end of the first trimester to determine whether the baby carries two mutations. Or they may decide to adopt or forego having children. </p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/ZkOLTfEyLXg?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">TedXTalks.</span></figcaption>
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<p>If a couple decide to continue a pregnancy, knowing ahead of time their baby will be affected allows them time to process and make lifestyle plans to accommodate for their changing circumstances and engage with support groups. Rare disease groups such as <a href="https://smaaustralia.org.au/support-services/">Spinal Muscular Atrophy Australia</a> provide support in care options, resources and choices for families living with spinal muscular atrophy. If therapies are available, it also allows for <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392137/">treatment of the disease from birth</a>. </p>
<p>As no screening test guarantees a healthy baby, genetic counselling is crucial to explain the limitations and risks to couples. <a href="https://www.youtube.com/watch?v=7yIW0L9dLCQ">Counselling</a> involves communicating complex genetic information clearly to couples, clarifying any doubts and misconceptions and more importantly to interpret and explain test results. </p>
<h2>Should all couples have this test?</h2>
<p>Our experience shows access to this kind of genetic testing can be challenging. Generally this is because health care professionals can be unaware such tests are available locally; or be unfamiliar with how blood should be collected, or where to send specimens for testing. </p>
<p>Preconception carrier screening tests have also been confused with other prenatal tests, particularly the non-invasive prenatal test (<a href="https://theconversation.com/australians-can-be-denied-life-insurance-based-on-genetic-test-results-and-there-is-little-protection-81335">NIPT</a>), by both parents and health care professionals. In this situation, parents may feel reassured their child does not have a genetic disease, but NIPT only tests for chromosomal problems (like Down Syndrome or trisomy 21) not single gene disorders. </p>
<p>This clearly shows awareness and education is critical among health care workers for preconception carrier screening programs to be successful.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/explainer-what-is-pre-pregnancy-carrier-screening-and-should-potential-parents-consider-it-79184">Explainer: what is pre-pregnancy carrier screening and should potential parents consider it?</a>
</strong>
</em>
</p>
<hr>
<p>Given the risk for an affected child for the three common recessive diseases is similar to Down syndrome, it may be considered carrier screening should be made available to everyone in Australia. But there are a number of issues that need to be addressed for this to happen.</p>
<p>These include consideration of the number of severe childhood disorders to be included for screening and who the target population would be. Studies are also required to inform the government of the most cost-effective method of offering such a test. </p>
<p>If a carrier screening program is to be implemented by the government, the infrastructure and clinical resources required to appropriately administer and sustain such testing must be explored to ensure all couples are informed and counselled as required. And <a href="http://www.health.gov.au/internet/msac/publishing.nsf/Content/17BAA5247F22729DCA25801000123C2C/$File/1165.1-FinalPSD-accessible.pdf">subsidy</a> of pre-implantation genetic diagnosis should also be considered for all carrier couples. </p>
<p>Pilot studies in different states may help explore how best a carrier screening program can fit into the different health systems in Australia.</p><img src="https://counter.theconversation.com/content/87083/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gina Ravenscroft receives funding from the National Health and Medical Research Council and the French Muscular Dystrophy Association (AFM). </span></em></p><p class="fine-print"><em><span>Michelle Farrar receives funding from Motor Neuron Diseases Research Institute of Australia </span></em></p><p class="fine-print"><em><span>Nigel Laing receives funding from The Australian National Health and Medical Research Council (NHMRC), the Association Francaise contre les Myopathies (AFM), the US Muscular Dystrophy Association (MDA), a Foundation Building Strength for Nemaline Myopathy (AFBS).
</span></em></p><p class="fine-print"><em><span>Royston Ong receives scholarship funding from the Australian Postgraduate Award and the Australian Genomic Health Alliance. </span></em></p>Cystic fibrosis, spinal muscular atrophy and fragile X syndrome are serious diseases, and most couples carrying the genetic mutations for these don’t know it. Should they all be tested?Gina Ravenscroft, Research Fellow in neuromuscular disease and genetics, The University of Western AustraliaMichelle Farrar, Senior lecturer in Paediatric Neurology, UNSW SydneyNigel Laing, Professor, The University of Western AustraliaRoyston Ong, Phd Student in Population Genetics, The University of Western AustraliaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/813802017-09-12T23:01:23Z2017-09-12T23:01:23ZWhy insurers are wrong about Canada’s genetic non-discrimination law<figure><img src="https://images.theconversation.com/files/185545/original/file-20170911-15801-k0ztl5.jpg?ixlib=rb-1.1.0&rect=30%2C3%2C2478%2C1667&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Canadians are overwhelmingly opposed to insurance companies having access to their genetic test results. A new Canadian law prevents insurers from using genetic information to determine coverage or pricing.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>Most western European countries have banned insurance companies from accessing privately held genetic test results on individuals since or even before the <a href="http://unesdoc.unesco.org/images/0013/001361/136112e.pdf">UNESCO Declaration on Human Genetic Data 2003.</a> </p>
<p>The United States passed legislation in 2008. It covers health insurance and employment, but not life and other forms of insurance, although some states have passed regulations about use of genetic tests by life insurers. </p>
<p>Canada was <a href="https://beta.theglobeandmail.com/life/health-and-fitness/health/bill-s-201-aims-to-end-genetic-discrimination-in-canada/article29494782/?ref=http://www.theglobeandmail.com&">the last member of the G7</a> to pass its own genetic discrimination law, Bill S-201, in May. It prevents insurance companies from using results of any genetic tests to determine coverage or pricing.</p>
<p>In other words, if you’re a woman with a genetic predisposition to breast cancer, a health or life insurer cannot deny coverage, restrict coverage or hike premiums.</p>
<p>So although life or health insurance companies may continue to ask for access to medical records, they’re prohibited from using information from genetic tests when offering insurance to potential clients.</p>
<h2>Why the controversy?</h2>
<p>That’s really what the bill is all about. So why has it been <a href="http://www.huffingtonpost.ca/2017/03/07/bill-s201-mps-to-debate-v_n_15207840.html">controversial</a> given Canada’s late entry into the game?</p>
<p>The Canadian Life and Health Insurance Association warned of higher costs and reduced coverage if the legislation passed. Insurers also argued no ban was needed; they would do it themselves via codes of conduct.</p>
<p>Others dismissed the ban as mere <a href="https://beta.theglobeandmail.com/news/national/anti-genetic-discrimination-bill-is-little-more-than-virtue-signalling/article34261843/?ref=http://www.theglobeandmail.com&">“virtue signalling”</a> and argued there’s no evidence Canadian insurance companies were engaging in genetic discrimination to begin with.</p>
<p>Despite the worldwide popularity of such bans, it’s still worth asking whether they’re a good idea. </p>
<p>Groups that include the <a href="http://ccgf-cceg.ca/en/home/">Canadian Coalition for Genetic Fairness (CCGF)</a> support the law, but <a href="https://www.clhia.ca/domino/html/clhia/clhia_lp4w_lnd_webstation.nsf/page/47B017C379E6898185257F70005B756C">there are still misgivings</a> in the insurance industry.</p>
<p>Insurance companies selling life insurance and other related products, including long-term care insurance, believe they should have access to the same information that their customers have. They say that’s in order to avoid high-risk individuals buying excessive amounts of insurance at the same price as those with low risks.</p>
<h2>Higher claims?</h2>
<p>The insurance industry argues the law will lead to higher claims costs and result in higher prices and a smaller market for the insurance industry, a phenomenon known as “adverse selection.”</p>
<p>Adverse selection occurs if more insurance is purchased by people deemed to be a higher risk — say, those with Huntington disease — than the average person with low risks.</p>
<p>That increases the overall claims costs to insurers, and if they can’t provide coverage to those with a higher risk of serious illnesses by charging a higher price, then those with scant health risks won’t buy insurance because it becomes too expensive. </p>
<p>Essentially, insurers argue, prices are driven up and the quantity of insurance available is reduced.</p>
<h2>Canadians opposed</h2>
<p>Organizations like the CCGF, however, represent the interests of people who would feel discriminated against if charged a higher price for an insurance product based on their inherited genetic makeup.</p>
<p><a href="https://beta.theglobeandmail.com/news/national/hands-off-my-genes-canadians-say/article1128996/?ref=http://www.theglobeandmail.com&">A 2003 poll by Pollara-Earnscliffe</a> found that a whopping 91 per cent of Canadian respondents agreed with the CCGF position that insurance companies should not be allowed to use genetic test results in pricing contracts. </p>
<p><a href="http://www.bmj.com/content/338/bmj.b2175">Another survey</a> suggested that 86 per cent of people with a family history of <a href="https://www.huntingtonsociety.ca/learn-about-hd/what-is-huntingtons/">Huntington disease,</a> for example, feared genetic discrimination. The same poll found 40 per cent reported actually experiencing genetic discrimination, mainly from life and long-term disability insurers.</p>
<p>If the insurance industry is correct, and significant amounts of high-risk people start buying up insurance as a result of the ban, then prices will become so high that many people simply won’t purchase coverage.</p>
<h2>‘Highly unlikely’ costs will rise</h2>
<p>As an economics professor who’s done <a href="https://www.priv.gc.ca/en/opc-actions-and-decisions/research/explore-privacy-research/2012/gi_hoy_201203/">extensive research on genetic discrimination</a>, I argue this scenario is highly unlikely. Studying the phenomenon of adverse selection has made up a large part of my research activity for more than three decades. </p>
<p>For a ban on insurers’ use of genetic test results to create a serious problem in insurance markets, it would require particular conditions:</p>
<ol>
<li><p>There would have to be a significant percentage of individuals seeking life insurance who have had genetic tests that determined they carry the genes for fatal diseases, or much higher future health costs for long-term care and other types of health insurance.</p></li>
<li><p>Having such information would have to spur people to purchase substantially more insurance than a typical consumer without such information. </p></li>
</ol>
<p>Actuarial evidence suggests that these conditions aren’t at play, so there won’t be a major impact on the average price of insurance. That suggests the objectionable phenomenon of genetic discrimination will, in fact, be thwarted by the new law. </p>
<h2>‘As many good genes as bad genes’</h2>
<p>I believe that Bill S-201 is an appropriate response to the concerns of citizens about genetic discrimination.</p>
<p>A Liberal party senator, James Cowan, should be congratulated for initiating the bill in the Senate, as should Liberal MP Robert Oliphant for presenting and championing it through the House of Commons. </p>
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<img alt="" src="https://images.theconversation.com/files/185547/original/file-20170911-20832-1p9gzjo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/185547/original/file-20170911-20832-1p9gzjo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=452&fit=crop&dpr=1 600w, https://images.theconversation.com/files/185547/original/file-20170911-20832-1p9gzjo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=452&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/185547/original/file-20170911-20832-1p9gzjo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=452&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/185547/original/file-20170911-20832-1p9gzjo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=567&fit=crop&dpr=1 754w, https://images.theconversation.com/files/185547/original/file-20170911-20832-1p9gzjo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=567&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/185547/original/file-20170911-20832-1p9gzjo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=567&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">Sen. James Cowan is seen here on Parliament Hill in June 2015.</span>
<span class="attribution"><span class="source">THE CANADIAN PRESS/Sean Kilpatrick</span></span>
</figcaption>
</figure>
<p>The Office of the Privacy Commissioner of Canada (OPCC) also acted responsibly in their mandate as ombudsman for Canadians’ privacy concerns by <a href="https://www.priv.gc.ca/en/opc-actions-and-decisions/research/explore-privacy-research/2011/gi_macdonald_201107/">commissioning several reports</a>, including <a href="https://www.priv.gc.ca/en/opc-actions-and-decisions/research/explore-privacy-research/2011/gi_macdonald_201107/">one by a highly knowledgeable actuary</a>, Prof. Angus Macdonald, and the economic analysis by myself and Maureen Durnin.</p>
<p>It is, of course, possible that in the future, the costs of genetic tests will become much lower, more genetic tests for diseases will become available and the current fraction of people who privately hold such information may become much larger. </p>
<p>So there may be, in the long run, reason to revisit this law. </p>
<p>But if there’s an explosion of genetic information across the population in the long term, it’s probable that most people will find that they have as many good genes as bad ones.</p>
<p>And that means there likely won’t be substantial differences among the risk levels for mortality or morbidity — a necessity if adverse selection becomes a problem for insurance markets.</p><img src="https://counter.theconversation.com/content/81380/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mike Hoy 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>Canadian insurance companies argue that a new law denying them access to genetic test results will raise the cost of insurance for everyone. That’s doubtful.Mike Hoy, Professor of Economics, University of GuelphLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/731102017-02-27T00:44:29Z2017-02-27T00:44:29ZSafe and ethical ways to edit the human genome<figure><img src="https://images.theconversation.com/files/158348/original/image-20170224-23000-tob9rr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Human genome editing raises a lot of questions. </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/255876943?src=raRdH4wR0Oftl9_tRKTL9g-1-13&size=huge_jpg">Gene sequence image via www.shutterstock.com.</a></span></figcaption></figure><p>The National Academies of Science and Medicine (NASEM) released a <a href="https://www.nap.edu/catalog/24623/human-genome-editing-science-ethics-and-governance">report</a> on Feb. 14 exploring the implications of new technologies that can alter the genome of living organisms, including humans. </p>
<p>Although scientists have been able to edit genes for several decades, new genome editing technologies are more efficient, more precise and far less expensive than previous ones. One of these techniques, known as CRISPR-Cas9, could allow for new applications ranging from editing viruses and bacteria to animals, plants and human beings. </p>
<p>For example, scientists could design <a href="http://news.berkeley.edu/2017/01/24/crispr-research-institute-expands-into-agriculture-microbiology/">pest-resistant plants</a>. They could modify the genome of animals, bacteria and <a href="http://www.nature.com/news/hiv-overcomes-crispr-gene-editing-attack-1.19712">viruses</a> to help fight diseases and plagues. </p>
<p>CRISPR could potentially be used by <a href="http://newatlas.com/home-crispr-gene-editing-kit/40362/">almost anybody</a> willing to tinker with the genome. This, and the fact that it can be used either for beneficial or harmful purposes, have raised fears that CRISPR could become a <a href="https://www.technologyreview.com/s/600774/top-us-intelligence-official-calls-gene-editing-a-wmd-threat/">weapon of mass destruction</a>.</p>
<p>CRISPR could also be used to modify the human genome. The big question scientists are wrestling with is whether these technologies should be used to make modifications in human reproductive cells. Changes made in these cells are heritable from one generation to the next, and are called germline modifications.</p>
<p>Some scientists working with these techniques called for a <a href="http://www.nature.com/news/don-t-edit-the-human-germ-line-1.17111">moratorium</a> for editing that could result in germline modifications. Others thought that a <a href="http://science.sciencemag.org/content/348/6230/36.full">prudent path</a> for using these technologies was needed.</p>
<p>The NASEM report did not endorse a moratorium. But it recommended that at least <a href="http://nationalacademies.org/cs/groups/genesite/documents/webpage/gene_177255.pdf">10 stringent conditions</a> should be met before authorizing this use. The report also said that more discussion – with wide public participation – was needed before proceeding with human germline modification. </p>
<p>I explore the ethical and policy questions raised by emerging technologies such as CRISPR at the <a href="https://scienceandsociety.duke.edu/">Duke Initiative for Science and Society</a>. I am particularly interested in how different countries regulate these technologies. </p>
<h2>What does the report say?</h2>
<p>For research using human cells and tissues, the <a href="http://nationalacademies.org/cs/groups/genesite/documents/webpage/gene_177259.pdf">NASEM Committee</a> said that existing regulatory and ethical frameworks were able to address the questions that might arise from genome editing. The same is true for genome editing of cells in the body that are not reproductive cells –called somatic cells – for therapeutic purposes.</p>
<p>So while clinical trials for modifications of somatic cells were given a green light, the modification of reproductive cells (eggs, sperm and embryos) which would lead to germline modifications, was given a <a href="http://www.sciencemag.org/news/2017/02/us-panel-gives-yellow-light-human-embryo-editing">yellow light</a> for the moment. </p>
<p>These types of genome modifications have raised fears about a <a href="http://dx.doi.org/doi:10.15779/Z38FM40">brave new world</a> of “designer babies.” </p>
<p>These questions are not new. The difference is that scientists are closer than ever to actually being able to significantly and accurately <a href="http://dx.doi.org/10.1007/s13238-015-0153-5">alter the human genome</a>.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/158349/original/image-20170224-22983-14ois3d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/158349/original/image-20170224-22983-14ois3d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/158349/original/image-20170224-22983-14ois3d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/158349/original/image-20170224-22983-14ois3d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/158349/original/image-20170224-22983-14ois3d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/158349/original/image-20170224-22983-14ois3d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/158349/original/image-20170224-22983-14ois3d.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">New gene editing technologies have raised ethical questions about ‘designer’ babies.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/144900970?src=eJaNOjLeVy2YHU3VVbSrHQ-1-4&size=huge_jpg">Babies image via www.shutterstock.com.</a></span>
</figcaption>
</figure>
<h2>Recommendations for germline modification</h2>
<p>The NASEM report concluded that it would be fine to proceed with the modification of germline cells only if three requirements are met. </p>
<p>One is that further research should prove that there are sufficient prospective benefits relative to the risks of using these techniques before starting clinical trials. </p>
<p>Another is that the public should be involved in a broad dialogue about the use of these technologies. </p>
<p>And a sound regulatory and oversight framework should be in place to guarantee that the following <a href="http://nationalacademies.org/cs/groups/genesite/documents/webpage/gene_177255.pdf">10 conditions</a> are met before using genome editing to alter sperm, eggs or embryos:</p>
<ol>
<li> that genome editing is used only when no other “reasonable alternatives” exist;<br></li>
<li> that it is only used to prevent a “serious disease or condition”; </li>
<li> that use is restricted to altering genes “that have been convincingly demonstrated to cause or strongly predispose to that disease or condition”; </li>
<li> that use is limited to converting genes into “versions that are prevalent in the population and are known to be associated with ordinary health with little or no evidence of adverse effects”; </li>
<li> that credible preclinical and/or clinical data on both potential risks and potential health benefits of the use of these technologies exist;</li>
<li> that the effects of these technologies on the health and safety of the research participant are subject to ongoing and serious oversight during the trial; </li>
<li> that a comprehensive plan for “long-term, multigenerational follow-up” that respects personal autonomy exists; </li>
<li> that a balance is achieved between ensuring maximum transparency and respecting patient privacy; </li>
<li> that both health and societal benefits and risks are continuously reassessed, including through the input provided by the public; and </li>
<li>that reliable oversight is put in place to prevent the use of these technologies for reasons going beyond the prevention of a “serious disease or condition.”</li>
</ol>
<p>Most of these conditions aim at ensuring that germline genome editing will be used only to prevent a serious disease, where no reasonable alternatives exist, and under strong supervision. Some of them will be very difficult to meet. For instance, how can the long term follow-up of children (and their children) born with the help of genome editing be guaranteed? This would be specially difficult with people traveling to other countries to access these technologies. </p>
<p>Finally, the use of genome editing for enhancement purposes was given a red light for the moment and should be subject to further and wider discussions.</p>
<h2>Genome modification in a globalized world</h2>
<p>The NASEM report cited <a href="https://www.pasteur.fr/en/institut-pasteur/history">Louis Pasteur</a> – a French microbiologist famous for his many discoveries, including the process of pasteurization – who once said “science has no homeland, because knowledge is the heritage of humanity.” The report and the human gene editing <a href="http://nationalacademies.org/gene-editing/index.htm">initiative</a> from the National Academy of Sciences and the National Academy of Medicine are paying special attention to international considerations.</p>
<p>An open question is whether the recommendations about human germline editing, which has been interpreted by some as an <a href="https://medium.com/@C_G_S/the-center-for-genetics-and-society-comments-on-new-human-gene-editing-report-e8786f9d5b8e#.wakru2fn9">endorsement</a> of the practice, are a good starting point for a wide international dialogue. </p>
<p>A <a href="https://dx.doi.org/10.1186/1477-7827-12-108">2014 study</a> found that 29 out of 39 surveyed countries have decided to ban the use of technologies to modify the human germline. Of these, countries such as Austria, Italy, Spain and the Netherlands have a ban in place. And others such as Argentina, Greece, Peru and South Africa have ambiguous regulations.</p>
<p>Other genetic modification techniques have been used to conceive babies free of genetic diseases carried by their parents. One such technique, <a href="https://theconversation.com/the-next-frontier-in-reproductive-tourism-genetic-modification-67132">mitochondrial replacement therapy</a>, has recently been used in <a href="http://www.nature.com/news/reports-of-three-parent-babies-multiply-1.20849">China</a>, <a href="https://www.newscientist.com/article/2107219-exclusive-worlds-first-baby-born-with-new-3-parent-technique/">Mexico</a> and <a href="http://www.cnn.com/2017/01/18/health/ivf-three-parent-baby-girl-ukraine-bn/">Ukraine</a> and will probably be used in the <a href="http://www.ncl.ac.uk/press/news/2016/12/worldsfirstmitochondriallicence/">U.K. soon</a>.</p>
<p>However, in the U.S., a rider included in a <a href="https://www.congress.gov/bill/114th-congress/house-bill/2029/text">Congressional Appropriations Act</a> in place until April 2017 forbids the FDA from considering any trials that will alter the human germline. Experience with <a href="https://newsatjama.jama.com/2015/11/05/jama-forum-selective-regrets-the-dickey-amendments-20-years-later/">other riders</a> shows that this ban could be extended indefinitely.</p>
<p>The report sought to develop “a framework based on fundamental, underlying principles that may be adapted and adopted by any nation.” But how could this framework be adopted by nations that currently ban any germline modification? </p>
<p>In a globalized world, patients can potentially cross borders for medical interventions that are not available in their own countries. This has already happened with mitochondrial replacement therapy. Some countries might decide <a href="http://dx.doi.org/10.1056/NEJMp1600891">to relax their standards</a> in the hope of attracting “tourist” patients or boosting their research capabilities. An international agreement to regulate these technologies would help to set a minimum set of standards that countries should comply with. </p>
<p>But it is unlikely that countries will reach any agreement in the near future. The report noted that different regulatory approaches could be tested in different countries until we better understand these technologies and the best way to regulate them. </p>
<p>Regardless of whether one believes that an international agreement is needed or feasible, international cooperation and dialogue seem to be essential components of good governance for new technologies.</p><img src="https://counter.theconversation.com/content/73110/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Rosa Castro does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>A new report from the National Academies of Science and Medicine outlines conditions that have to be met before gene editing that results in heritable genomic changes can be considered.Rosa Castro, Postdoctoral Associate in Science and Society, Duke UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/514742015-12-02T19:29:41Z2015-12-02T19:29:41ZFive reasons we should embrace gene-editing research on human embryos<figure><img src="https://images.theconversation.com/files/104001/original/image-20151202-14464-o2f6h4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Future people would be grateful if their disease is cured, rather than being replaced by a different healthier or non-disabled person.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/40765798@N00/2396559684/">sabianmaggy/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Scientists from around the world are <a href="http://www.nationalacademies.org/gene-editing/index.htm">meeting in Washington this week to debate</a> how best to proceed with research into gene-editing technology. </p>
<p><a href="https://theconversation.com/explainer-crispr-technology-brings-precise-genetic-editing-and-raises-ethical-questions-39219">Gene editing</a> is a new precise form of genetic engineering. It uses enzymes from bacteria to locate genes within DNA and delete or replace them. In early 2015, Chinese scientists used it <a href="http://www.ncbi.nlm.nih.gov/pubmed/25894090">to modify human embryos</a> as a first step towards preventing the genetic transmission of a blood disease. </p>
<p>Many people, including scientists, are worried about creating genetically modified humans. They’re worried about numerous things: genetic mistakes being passed on to the next generation; the creation of designer babies who are more intelligent, more beautiful or more athletic; and the possibility of causing severe growth abnormalities or cancer.</p>
<p>While these are <a href="https://theconversation.com/why-we-can-trust-scientists-with-the-power-of-new-gene-editing-technology-51480">valid concerns</a>, they don’t justify a ban on research. Indeed, such research is a moral imperative for five reasons.</p>
<h2>1. Curing genetic diseases</h2>
<p>Gene editing could be used to cure genetic diseases such cystic fibrosis or thalassaemia (the blood disease that the Chinese researchers were working to eliminate). At present, there are no cures for such diseases. </p>
<p>Detractors say selection of healthy embryos or fetuses via genetic testing is preferable. But such genetic tests require abortion or embryo destruction, which is also objectionable to some people. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/103997/original/image-20151202-14440-wuneo6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/103997/original/image-20151202-14440-wuneo6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=428&fit=crop&dpr=1 600w, https://images.theconversation.com/files/103997/original/image-20151202-14440-wuneo6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=428&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/103997/original/image-20151202-14440-wuneo6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=428&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/103997/original/image-20151202-14440-wuneo6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=538&fit=crop&dpr=1 754w, https://images.theconversation.com/files/103997/original/image-20151202-14440-wuneo6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=538&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/103997/original/image-20151202-14440-wuneo6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=538&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Gene-edited embryonic stem cell lines that cause or protect against disease could help us understand the origins of disease.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/11304375@N07/6867005898/">Image Editor/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<p>What’s more, genetic selection doesn’t benefit patients - it’s not a cure. It merely brings a different person, who is free from disease, into existence. Future people would be grateful if their disease is cured, rather than being replaced by a different healthier or non-disabled person.</p>
<h2>2. Dealing with complex diseases</h2>
<p>Most common human diseases, such as heart disease or schizophrenia, don’t just involve one gene that’s abnormal (such as in cystic fibrosis). They’re the result of many, sometimes hundreds, of genes combining to cause ill health. </p>
<p>Genetic selection technologies can’t eliminate genetic predispositions to these diseases. In principle, gene editing could be used to reduce the risk of heart disease or Alzheimer’s disease.</p>
<h2>3. Delaying or stopping ageing</h2>
<p>Each day, thousands of people die from age-related causes. Cardiovascular disease (strongly age-related) is emerging as the biggest cause of death in the developing world. Ageing kills 30 million every year. </p>
<p>That makes it the most under-researched cause of death and suffering relative to its significance. Indeed, age-related diseases, such as heart disease or cancer, are really the symptoms of an underlying disease: ageing.</p>
<p>Gene editing could delay or arrest ageing; this has already been achieved in mice. Gene editing might offer the prospect of humans living twice as long, or perhaps even hundreds of years, without loss of memory, frailty or impotence.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/103996/original/image-20151202-14464-ovh5mb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/103996/original/image-20151202-14464-ovh5mb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=461&fit=crop&dpr=1 600w, https://images.theconversation.com/files/103996/original/image-20151202-14464-ovh5mb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=461&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/103996/original/image-20151202-14464-ovh5mb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=461&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/103996/original/image-20151202-14464-ovh5mb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=580&fit=crop&dpr=1 754w, https://images.theconversation.com/files/103996/original/image-20151202-14464-ovh5mb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=580&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/103996/original/image-20151202-14464-ovh5mb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=580&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Age-related diseases, such as heart disease or cancer, are really the symptoms of an underlying disease: ageing.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/neilmoralee/15680209728/">Neil Moralee/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<h2>4. Stopping the genetic lottery</h2>
<p>The fourth reason for supporting gene-editing research on human embryos is the flip side of the designer baby objection. People worry that such technology could be used to create a master race, like fair-haired, blue-eyed “Aryans”. </p>
<p>What this concern neglects is that the biological lottery – i.e. nature – has no mind to fairness. Some are born gifted and talented, others with short painful lives or severe disabilities. While we may worry about the creation of a genetic masterclass, we should also be concerned about those who draw the short genetic straw. </p>
<p>Diet, education, special services and other social interventions are used to correct natural inequality. Ritalin, for example, is prescribed to up to 10% of children with poor self-control to improve their educational prospects and behavioural control. </p>
<p>Gene editing could be used as a part of public health care for egalitarian reasons: to benefit the worst off. People worry that such technologies will be used to benefit only those who can afford it – keep reading for why they shouldn’t.</p>
<h2>5. Making disease treatments less costly</h2>
<p>Gene editing of human embryos could enable greater understanding of disease and new treatments that don’t modify human beings.</p>
<p>Gene-edited embryonic stem cell lines that cause or protect against disease could help us understand the origins of disease. Other edited stem cells could help treatment - imagine blood cells that kill and replace leukemic cells. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/103995/original/image-20151202-14461-lig1aq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/103995/original/image-20151202-14461-lig1aq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/103995/original/image-20151202-14461-lig1aq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/103995/original/image-20151202-14461-lig1aq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/103995/original/image-20151202-14461-lig1aq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=504&fit=crop&dpr=1 754w, https://images.theconversation.com/files/103995/original/image-20151202-14461-lig1aq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=504&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/103995/original/image-20151202-14461-lig1aq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=504&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Concerns about gene-editing technology being used to create designer babies neglects that the biological lottery - or nature - has no mind to fairness.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/booleansplit/3856718374/">Robert S. Donovan/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<p>This knowledge could be used to develop treatments for diseases, including drugs, that can be produced cheaply. And that would reduce, rather than increase, inequality.</p>
<h2>The moral imperative</h2>
<p>There are valid concerns about applying gene editing to create live born babies. Such reproductive applications could be banned. </p>
<p>But the technology could be used for therapeutic research: to understand disease and develop new treatments. And any constraints we place on it must keep this in mind. </p>
<p>Laws to prevent reproductive gene editing may be justified on the basis of safety concerns but a ban on therapeutic gene editing cannot.</p>
<p>To ban it would be to ignore a great deal of good that can be done for a great many people, including some of the most vulnerable.</p><img src="https://counter.theconversation.com/content/51474/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Julian Savulescu does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Experts from around the world are in the US to discuss the scientific, ethical and governance issues linked to human gene editing. Here are five reasons they shouldn’t ban research in the field.Julian Savulescu, Sir Louis Matheson Distinguishing Visiting Professor at Monash University, Uehiro Professor of Practical Ethics, University of OxfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/475342015-09-23T04:29:05Z2015-09-23T04:29:05ZExplainer: South Africa’s challenges in the search for genes causing eye disease<figure><img src="https://images.theconversation.com/files/95684/original/image-20150922-16679-vu3k9q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A visually impaired young girl reads a Braille notice. Retinal dysfunction results in one in 3 500 people suffering night blindness, loss of peripheral vision and later complete blindness.</span> <span class="attribution"><span class="source">Reuters/Amr Abdallah Dalsh </span></span></figcaption></figure><p>The retina is a thin, light-sensitive tissue at the back of the eye. It captures light and converts it into a chemical signal which travels to the brain, ultimately registering as vision. The retina is actually part of the central nervous system and is considered part of the brain. The ‘photoreceptors’ or light-sensitive nerve cells of the retina, are divided into the rod cells and the cone cells, reflecting their actual shapes. </p>
<p>There are about 120 million rod cells spread throughout the retina. These are responsible for black and white vision, and allow vision in low-light conditions. Then the six million cone cells are located in the centre of the retina, in an area called the macula, and are responsible for colour vision and detailed central vision.</p>
<p>A group of diseases collectively called inherited retinal degenerative <a href="http://www.humangenetics.uct.ac.za/wp-content/uploads/2013/02/Fact-Sheet-8-Inherited-RD.pdf">disorders</a> are caused by genetic defects which cause vision loss. This may result in total blindness. These disorders are caused by genetic changes or mutations and are inherited within families. </p>
<p>These genetic mutations result in different disorders. Gene defects affecting mainly the rod photoreceptors cause retinitis pigmentosa. As a result patients experience night blindness and loss of peripheral vision, causing a tunnel-like vision. Genetic mutations causing a primary loss of cone photoreceptors result in <a href="http://www.humangenetics.uct.ac.za/wp-content/uploads/2013/02/Fact-Sheet-6-Stargardt-Dystrophy.pdf">Stargardt disease</a> or macular degeneration and cause a loss of central vision.</p>
<h2>A rare disease without a cure</h2>
<p>Although genetic diseases are generally rare, globally about 1 in 3500 people suffer from retinal degenerative disorders. In South Africa and Africa, exact statistics around retinal degenerative disorders are not available. We estimate that at least 14 500 South Africans suffer from vision loss because of these disorders. This conservative estimate is based on reported retinal degenerative disorders cases but each disorder has a different incidence rate so this number is likely higher.</p>
<p>There is currently no cure for retinal degenerative disorders but many gene therapies for these diseases are being established. In gene therapy the mutation in a gene has been corrected and is inserted into a patient’s cells as a treatment for disease. </p>
<p>There are at least eight clinical trials across the globe in countries such as the US. These trials are testing the safety and efficacy of gene therapies in patients with these disorders.</p>
<h2>Advances in treatment</h2>
<p>The use of gene therapy for <a href="http://www.nih.gov/researchmatters/june2013/06242013eye.htm">eye diseases</a> are further advanced than for most other diseases. This is because the eye is small, easily accessible and self-contained. This means small amounts of treatment with the corrected gene can be inserted directly where needed. </p>
<p>There is little worry about unwanted off-target effects - where other sites in the genome are unintentionally modified - because the treatment does not cross the blood-brain barrier and cannot enter the rest of the body. This is the biggest concern within the gene therapy field.</p>
<p>But to participate in any of these trials, the patient must have a confirmed genetic diagnosis, meaning a confirmed mutation in the gene which is to be replaced or repaired.</p>
<p>The genetic cause of these disorders must be identified in South Africans for the clinical trials to come to the country - a process that <a href="http://www.retinasa.org.za/">Retina South Africa</a> has been intricately involved in. </p>
<h2>Complicated genetics in retinal dysfunction</h2>
<p>There are several challenges in identifying the genes causing retinal degenerative disorders in families. </p>
<p>The first is that the genetics of these disorders are complex. There are more than 280 genes reported to be linked to these disorders. Mutations in any one of those genes can cause these disorders. There are potentially hundreds of mutations in each gene. Some genes are obvious candidates involved in the cells or biological pathways required for vision. Others are unlikely culprits and are responsible for normal functioning of cells in the body. They cause no other disease besides retinal dysfunction and subsequent vision loss. </p>
<p>Secondly, retinal degenerative disorders can be inherited in families in different ways. They can also manifest as part of a syndrome such as <a href="http://www.humangenetics.uct.ac.za/wp-content/uploads/2013/02/Fact-Sheet-5-Usher-Syndrome.pdf">Usher syndrome</a>, which involves both vision impairment and hearing loss. </p>
<p>An ophthalmologist cannot tell from a clinical examination what the genetic cause of the disorder is. Patients with different mutated genes can end up with the same clinical disease. For example, more than 55 different genes can each cause retinis pigmentosa. What further complicates this is within families, people with the same genetic mutation can have different symptoms.</p>
<p>And as the disease progresses over time the symptoms change, which can result in a change of the disease diagnosis. </p>
<p>Making a genetic diagnosis is challenging and requires detailed clinical information and family history. But having a genetic diagnosis is essential to participate in any gene therapy based clinical trials.</p>
<h2>The South African challenge</h2>
<p>Finding a genetic diagnosis is also complicated by the unique genetic diversity of Africans. Most white South Africans originated from European settlers so our testing for the specific genetic mutations reported internationally has been successful over the last 26 years of research at the University of <a href="http://www.humangenetics.uct.ac.za/">Cape Town</a>. </p>
<p>But there is less success with this approach for black South Africans. African populations have vast genetic diversity, as a result of admixture between populations and migration around, out of and back into Africa. </p>
<p>Our current research with Professor Anand Swaroop at the National Eye <a href="https://nei.nih.gov">Institute</a> in the US uses the next generation of DNA sequencing technology to sequence the entire coding region of the human genome, known as the exome, in black South Africans. </p>
<p>The exome is the one to two percent of the human genome containing active portions of all 20 000 known human genes. By sequencing the exome of this unique patient population group, we hope to identify their genetic basis of retinal degenerative diseases, which may have relevance to the continent as a whole. </p>
<p>This is a new technology and local scientists require collaboration and training in the analysis, as well as major computational resources. It is an approach which does not rely purely on our existing knowledge of retinal degenerative disorder genes but includes all human genes, both likely and unlikely candidates.</p><img src="https://counter.theconversation.com/content/47534/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Funding for this research project is provided by the University of Cape Town, the Medical Research
Council of South Africa and the lay support society Retina South Africa.</span></em></p>Today is the start of World Retinal Week. Establishing retinal degenerative disorders in Africa is challenged by the unique genetic diversity of Africans.Lisa Roberts, Medical Biological Scientist: Scientific Officer and Project Leader of the Retinal Degenerative Disorders research group, Division of Human Genetics, UCT, University of Cape TownLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/453342015-08-17T05:32:56Z2015-08-17T05:32:56ZOur ‘Rosetta Stone’ gene could unlock the secrets of schizophrenia<figure><img src="https://images.theconversation.com/files/91818/original/image-20150813-21432-1raz7ax.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Schizophrenia affects around <a href="http://www.nimh.nih.gov/health/topics/schizophrenia/index.shtml">1% of the global population</a> and can cause paranoia, hallucinations and a breakdown in patients’ thought processes, with a huge impact on their ability to carry out everyday tasks. Around 50% of people who suffer with the condition <a href="http://www.ncbi.nlm.nih.gov/pubmed/12511175">attempt suicide</a>. </p>
<p>There are currently relatively few treatments for the condition – and the drugs that are available can have <a href="http://www.rcpsych.ac.uk/healthadvice/treatmentswellbeing/antipsychoticmedication.aspx">unwanted side effects</a>, such as shakiness, weight gain and decreased libido. However, genetics may hold the key to developing more effective treatments. My colleagues and I <a href="http://www.sciencemag.org/content/349/6246/424">recently discovered</a> that one specific gene may allow us to decode the function of all genes involved in the disease. This “Rosetta Stone” gene has revealed a period early in the brain’s development when treatments may be most effective in preventing schizophrenia manifesting in the first place.</p>
<p>Mental health conditions are among the most challenging medical problems we face as scientists, partly because of the complexity of the biology underlying thought processes and partly because studying a living brain is very difficult. However, <a href="http://www.nimh.nih.gov/news/science-news/2013/five-major-mental-disorders-share-genetic-roots.shtml">recent studies</a> <a href="http://bjp.rcpsych.org/content/198/3/173">have begun to make</a> some headway in understanding the biology of mental health conditions by looking at the gene mutations carried by people diagnosed with such problems.</p>
<h2>Origins of genetic disease</h2>
<p>Gene mutations are present in all the cells in the body and can be examined by taking a blood sample. We now know that many of the genes involved in mental health conditions carry instructions for creating the proteins in the brain’s synapses. These are the connections between neurons that allow them to communicate with one another.</p>
<p>But despite knowing about hundreds of mutations associated with schizophrenia, we are relatively in the dark about what they all do. <a href="http://www.nature.com/nature/journal/v460/n7256/abs/nature08185.html">Many different mutations</a> can give rise to the same apparent condition. On the other hand, no single gene mutation necessarily gives rise to a discernible mental health problem.</p>
<p>One gene we do have some certainty about is known as “<a href="http://www.nature.com/mp/journal/v13/n1/full/4002106a.html">disrupted in schizophrenia gene 1</a>” (DISC1). It relates to a protein that, when mutated, can give rise to a number of mental health conditions including schizophrenia, bipolar disorder, major clinical depression and autism.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/91821/original/image-20150813-21432-2y1zp8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/91821/original/image-20150813-21432-2y1zp8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/91821/original/image-20150813-21432-2y1zp8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/91821/original/image-20150813-21432-2y1zp8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/91821/original/image-20150813-21432-2y1zp8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/91821/original/image-20150813-21432-2y1zp8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/91821/original/image-20150813-21432-2y1zp8.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">Thought breakdown.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
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</figure>
<p>While schizophrenia may be inherited, the probability of inheritance from a mutation carried by one parent alone is relatively low. In contrast, DISC1 mutations are highly <a href="http://medical-dictionary.thefreedictionary.com/penetrance">penetrant</a>, meaning that carrying the mutation is highly likely to give rise to the characteristic problem.</p>
<p>This makes DISC1 a very useful experimental tool, because if a laboratory animal such as a mouse carries the mutation, it is highly likely to exhibit the functional problem and to give rise to offspring with the same problem. Studying DISC1 solves two problems at once: we do not need to look at human neurons because we can use mice instead – and we only need a single mutation rather than the several gene mutations that normally give rise to the condition.</p>
<p>In our studies on DISC1 mice, we have found that the gene has an important function during an early period of brain development. If you impair the function of DISC1 for just two days during the second week after birth, the animal grows up with a lack of brain plasticity (the ability to change neural pathways over time) in the synapses that were trying to form at the time.</p>
<h2>Targeting schizophrenia’s vulnerable period</h2>
<p>Different parts of the brain may mature at different times, but most cortical areas go through a similar sequence of development. Therefore, different areas are all likely to go through the vulnerable period at some point in their development. One of the challenges for the future is to discover what these “critical periods” are for different areas of the brain. </p>
<p>So how can studying DISC1 help us decode what is going wrong with other genes in schizophrenia? Our thought is that we may have identified a critical period in development, which is a common vulnerable period for all – or at least many – of the genes identified as risk factors in schizophrenia. DISC1 mutations have also been linked to autism and Asperger’s syndrome, suggesting that the developmental effects of DISC1 could also be important for understanding these mental health conditions.</p>
<p>The interaction between gene mutations and brain development may have made it difficult to understand how the long list of risk factors can cause problems in the adult brain. Now we know when to study the function of other risk factors and what the outcome is for adult function. We hope this will allow us to throw some light on what the other genes involved in schizophrenia are doing (or doing wrong) during development to give rise to the debilitating condition of schizophrenia.</p><img src="https://counter.theconversation.com/content/45334/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kevin Fox receives funding from the Medical Research Council</span></em></p>Scientists have discovered that a single gene may reveal a weakness in the development of schizophrenia that could help doctors prevent the condition.Kevin Fox, Professor of neuroscience, Cardiff UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/394662015-03-31T05:31:36Z2015-03-31T05:31:36ZGenome editing poses ethical problems that we cannot ignore<figure><img src="https://images.theconversation.com/files/76485/original/image-20150330-1274-1k3sjfu.jpg?ixlib=rb-1.1.0&rect=0%2C209%2C5000%2C4056&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">In the future, our DNA could be different by design.</span> <span class="attribution"><span class="source">DNA by Seamartini Graphics/www.shutterstock.com</span></span></figcaption></figure><p>The ability to precisely and accurately change almost any part of any genome, even in complex species such as humans, may soon become a reality through genome editing. But with great power comes great responsibility – and few subjects elicit such heated debates about moral rights and wrongs.</p>
<p>Although genetic engineering techniques have been around for some time, <a href="https://theconversation.com/explainer-crispr-technology-brings-precise-genetic-editing-and-raises-ethical-questions-39219">genome editing</a> can achieve this with lower error rates, more simply and cheaply than ever – although the technology is certainly not yet perfect.</p>
<p>Genome editing offers a greater degree of control and precision in how specific DNA sequences are changed. It could be used in basic science, for human health, or improvements to crops. There are a variety of techniques but clustered regularly inter-spaced short palindromic repeats, or <a href="https://www.addgene.org/CRISPR/guide/">CRISPR</a>, is perhaps the foremost.</p>
<p>CRISPR has <a href="http://www.npr.org/blogs/health/2015/03/20/394311141/scientists-urge-temporary-moratorium-on-human-genome-edits">prompted recent calls for a genome editing moratorium</a> from a group of concerned US academics. Because it is the easiest technique to set up and so could be quickly and widely adopted, the fear is that it may be put into use far too soon – outstripping our <a href="http://nuffieldbioethics.org/wp-content/uploads/Genome-Editing-Briefing-Paper-Newson-Wrigley.pdf">understanding of its safety implications</a> and preventing any opportunity to think about how such powerful tools should be controlled.</p>
<h2>The ethics of genetics, revisited</h2>
<p>Ethical concerns over genetic modification are not new, <a href="http://www.councilforresponsiblegenetics.org/ViewPage.aspx?pageId=101">particularly when it comes to humans</a>. While we don’t think genome editing gives rise to any completely new ethical concerns, there is more to gene editing than just genetic modification.</p>
<p>First, there is no clear consensus as to whether genome editing is just an incremental step forward, or whether it represents a disruptive technology capable of overthrowing the current orthodoxy. If this is the case – and it’s a very real prospect – then we will need to carefully consider genome editing’s ethical implications, including whether current regulation is adequate.</p>
<p>Second, there are significant ethical concerns over the potential scope and scale of genome editing modifications. As more researchers use CRISPR to achieve more genome changes, the implications shift. Our consideration of a technology that is rarely used and then only in specific cases will differ from one that is widely used and put to all sorts of uses.</p>
<p>Should we reach this tipping point, we will have to revisit the conclusions of the first few decades of the genetic modification debate. Currently modifying plants, some animals, and non-inheritable cells in humans is allowed under strict controls. But modifications that alter the human germ-line are not allowed, with the exception of the recent decision in the UK to allow <a href="http://www.parliament.uk/business/news/2015/february/commons-debate-statutory-instrument-on-mitochondrial-donation/">mitochondrial replacement</a>. </p>
<p>While this may mean weighing up potential benefits, risks and harms, as the potential applications of genome editing are so broad even this sort of assessment isn’t straightforward.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/76483/original/image-20150330-1256-1jskjd7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/76483/original/image-20150330-1256-1jskjd7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=596&fit=crop&dpr=1 600w, https://images.theconversation.com/files/76483/original/image-20150330-1256-1jskjd7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=596&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/76483/original/image-20150330-1256-1jskjd7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=596&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/76483/original/image-20150330-1256-1jskjd7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=749&fit=crop&dpr=1 754w, https://images.theconversation.com/files/76483/original/image-20150330-1256-1jskjd7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=749&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/76483/original/image-20150330-1256-1jskjd7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=749&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">What patterns can genetic surgeons weave?</span>
<span class="attribution"><span class="source">too human by lonely/www.shutterstock.com</span></span>
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<h2>Use for good and for ill</h2>
<p>Genome editing techniques have so far been used to change genomes in individual cells and in entire (non-human) organisms. Benefits have included better targeted gene therapy in animal models of some diseases, such as <a href="http://www.nature.com/ncomms/2015/150218/ncomms7244/full/ncomms7244.html">Duchenne Muscular Dystrophy</a>. It’s also hoped that it will lead to a better understanding of the structure, function and regulation of genes. Genetic modification through genome editing of plants has already created herbicide- and infection-resistant crops. </p>
<p>But more contentious is how genome editing might be used to change traits in humans. While this has been the basis for many works of fiction, in real life our capacity to provide the sort of genetic engineering seen in films and books such as <a href="http://www.rogerebert.com/reviews/gattaca-1997">Gattaca</a> and <a href="http://www.imdb.com/title/tt0080468">Brave New World</a> has been substantially limited. </p>
<p>Genome editing potentially changes this, presenting us with the very real possibility that any aspect of the human genome could be manipulated as we desire. This could mean eliminating harmful genetic conditions, or enhancing traits deemed advantageous, such as resistance to diseases. But this ability may also open the door to eugenics, where those with access to the technology could select for future generations based on traits considered merely desirable: eye, skin or hair colour, or height. </p>
<h2>Permanent edits</h2>
<p>The concern prompting the US academics’ call for a moratorium is the potential for <a href="http://www.nature.com/news/don-t-edit-the-human-germ-line-1.17111">altering the human germ-line</a>, making gene alterations inheritable by our children. <a href="ghr.nlm.nih.gov/handbook/therapy/genetherapy">Gene therapies</a> that produce non-inheritable changes in a person’s genome are ethically accepted, in part because there is no risk for the next generation if things go wrong. However to date only one disease – <a href="http://www.scid.net/">severe combined immunodeficiency</a> – has been cured by this therapy.</p>
<p>Germ-line alternations pose much greater ethical concerns. A mistake could harm future individuals by placing that mistake in every cell. Of course the flip-side is that, if carried out safely and as intended, germ-line alterations could also provide potentially permanent solutions to genetic diseases. No research is yet considering this in humans, however. </p>
<p>Nevertheless, even if changes to the germ-line turn out to be safe, the underlying ethical concerns of scope and scale that genome editing brings will remain. If a technique can be used widely and efficiently, without careful oversight governing its use, it can readily become a new norm or an expectation. Those unable to access the desired genetic alterations, be they humans with diseases, humans without enhanced genetic characteristics, or farmers without genetically modified animals or crops, may all find themselves gravely and unfairly disadvantaged.</p><img src="https://counter.theconversation.com/content/39466/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Anthony Wrigley has received funds from the Nuffield Council on Bioethics to write a briefing paper on the scientific, ethical and policy issues arising in genome editing, co-authored with Ainsley Newson. The views expressed in this article are those of the authors and do not represent the views of the Nuffield Council on Bioethics.</span></em></p><p class="fine-print"><em><span>Ainsley Newson has received funds from the Nuffield Council on Bioethics to write a briefing paper on the scientific, ethical and policy issues arising in genome editing; co-authored with Anthony Wrigley. The views expressed in this article are those of the authors and do not represent the views of the Nuffield Council on Bioethics.</span></em></p>That genetic editing techniques have become as straightforward as they have poses questions for how we want them to be used.Anthony Wrigley, Senior Lecturer in Ethics, Keele UniversityAinsley Newson, Senior Lecturer in Bioethics, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/392192015-03-26T10:29:36Z2015-03-26T10:29:36ZExplainer: CRISPR technology brings precise genetic editing – and raises ethical questions<figure><img src="https://images.theconversation.com/files/76029/original/image-20150325-14494-1xgt7jo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A powerful new genetic engineering technique allows scientists to precisely cut out and replace DNA in genes. </span> <span class="attribution"><a class="source" href="http://newscenter.berkeley.edu/2015/03/19/scientists-urge-caution-in-using-new-crispr-technology-to-treat-human-genetic-disease/">Jennifer Doudna/University of California Berkeley</a></span></figcaption></figure><p>A group of leading biologists earlier this month called for a <a href="http://www.sciencemag.org/content/early/2015/03/18/science.aab1028">halt</a> to the use of a powerful new gene editing technique on humans. Known by the acronym CRISPR, the method allows precise editing of genes for targeted traits, which can be passed down to future generations. </p>
<p>With this explainer, we’ll look at where this technique came from, its potential and some of the issues it raises.</p>
<h2>Surgical precision</h2>
<p>CRISPR stands for clustered regularly interspaced short palindromic repeats, which is the name for a natural defense system that bacteria use to fend off harmful infections. </p>
<p>Bacteria are infected by other microorganisms, called <a href="http://www.cellsalive.com/phage.htm">bacteriophages</a>, or phages. The intricate details of the mechanism were elucidated around 2010 by two research groups led by Dr Doudna of the University of California Berkeley and Dr Charpentier of Umeå University in Sweden. </p>
<p>The CRISPR system recognizes specific patterns of DNA from the foreign invaders and decapacitates them by cutting the invader’s DNA into pieces. The way that the bacteria target specific DNA and cleave it gave scientists a hint of its potential in other applications. </p>
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<p>In 2013, two research groups, one lead by Dr Zhang of Massachusetts of Institute of Technology and the other by Dr Church of Harvard University, successfully modified this basic mechanism and turned it into a powerful tool that can now cut human genomic DNA at any desired location. </p>
<p>The ability to cut DNA or genes at specific locations is the basic requirement to modify the genome structure. Changes can be made in the DNA around the cleavage site which alter the biological features of the resulting cells or organisms. It is the equivalent of a surgical laser knife, which allows a surgeon to cut out precisely defective body parts and replace them with new or repaired ones. </p>
<h2>Tool for gene discovery</h2>
<p>Scientists have long sought after this sort of genome editing tools for living cells. Two other technologies, called <a href="http://en.wikipedia.org/wiki/Zinc_finger_nuclease">zinc-finger nucleases</a> and <a href="http://en.wikipedia.org/wiki/Transcription_activator-like_effector_nuclease">TALEN</a> (transcription activator-like effector nuclease) are available to achieve the same result. However, the CRISPR technology is much easier to generate and manipulate. This means that most biological research laboratories can carry out the CRISPR experiments. </p>
<p>As a result, CRISPR technology has been quickly adopted by scientists all over the world and put it into various tests. It has been demonstrated to be effective in genome editing of most experimental organisms, including cells derived from insects, plants, fish, mice, monkeys and humans. </p>
<p>Such broad successes in a short period of time imply we’ve arrived at a new genome editing era, promising fast-paced development in biomedical research that will bring about new therapeutic treatments for various human diseases. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/76030/original/image-20150325-14523-1fjj4o2.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/76030/original/image-20150325-14523-1fjj4o2.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/76030/original/image-20150325-14523-1fjj4o2.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=634&fit=crop&dpr=1 600w, https://images.theconversation.com/files/76030/original/image-20150325-14523-1fjj4o2.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=634&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/76030/original/image-20150325-14523-1fjj4o2.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=634&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/76030/original/image-20150325-14523-1fjj4o2.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=796&fit=crop&dpr=1 754w, https://images.theconversation.com/files/76030/original/image-20150325-14523-1fjj4o2.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=796&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/76030/original/image-20150325-14523-1fjj4o2.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=796&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Jennifer Doudna from the University of California Berkeley, who was one a co-inventor of the CRISPR, recently called for caution in using the gene-editing technology on human cells.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/departmentofenergy/16845913352">US Department of Energy</a></span>
</figcaption>
</figure>
<p>The CRISPR technology offers a novel tool for scientists to address some of the most fundamental questions that were difficult, if not impossible, to address before. </p>
<p>For instance, the whole human genomic DNA sequence had been deciphered many years ago, but the majority of information embedded on the DNA fragments are largely unknown. Now, the CRISPR technology is enabling scientists to study those gene functions. By eliminating or replacing specific DNA fragments and observing the consequences in the resulting cells, we can now link particular DNA fragments to their biological functions.</p>
<p>Recently, cells and even whole animals with desired genome alterations have successfully been generated using the CRISPR technology. This has proven highly valuable in various biomedical research studies, such as understanding the cause and effect relationship between specific DNA changes and human diseases. Studying DNA in this way also sheds light on the mechanisms underlying how diseases develop and provides insights for developing new drugs that eliminate specific disease symptoms. </p>
<p>With such profound implications in medical sciences, many biotech and pharmaceutical companies have now licensed the CRISPR technology to develop commercial products. </p>
<p>For example, a biotech company, Editas Medicine, was founded in 2013 with the specific goal of creating treatments for hereditary human diseases employing the CRISPR technology. </p>
<p>However, products derived from the use of CRISPR technology are yet to hit the market with FDA approval. </p>
<h2>Call for ethical guidelines</h2>
<p>With the CRISPR technology, scientists can now alter the genome composition of whole organisms, including humans, through manipulating reproductive cells and fertilized eggs or embryos. Those particular genetic traits are then passed down through generations. This brings hope to cure genetic defects that cause various hereditary human diseases, such as cystic fibrosis, haemophilia, sickle-cell anemia, Down syndrome and so on. </p>
<p>Unlike the current approaches of gene therapy which temporarily fix defective cells or organs through the introduction of corrected or functional genes, the CRISPR technology promises to correct the defect in the reproductive cells, producing progenies that are free of the defective gene. In other words, it can eliminate the root causes of hereditary human diseases. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/76031/original/image-20150325-14500-1rgyshg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/76031/original/image-20150325-14500-1rgyshg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/76031/original/image-20150325-14500-1rgyshg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/76031/original/image-20150325-14500-1rgyshg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/76031/original/image-20150325-14500-1rgyshg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/76031/original/image-20150325-14500-1rgyshg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/76031/original/image-20150325-14500-1rgyshg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/76031/original/image-20150325-14500-1rgyshg.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"></span>
<span class="attribution"><span class="source">DNA helix via www.shutterstock.com</span></span>
</figcaption>
</figure>
<p>In theory,then, hereditary features that people consider advantageous, such as higher intelligence, better body appearance and longevity, can be introduced into an individual’s genome through CRISPR mediated reproductive cell modifications as well.</p>
<p>However, scientists do not yet fully understand all the possible side effects of editing human genomes. It is also the case, that there is no clear law to regulate such attempts. </p>
<p>That’s why groups of prominent scientists in the field have <a href="http://www.sciencemag.org/content/early/2015/03/18/science.aab1028.full">recently initiated calls</a> for ethical guidelines for doing such modifications of reproductive cells. The fear being that uncontrolled practice might bring about unforeseen disastrous outcomes in long run. </p>
<p>The guidelines call for a strong discouragement of any attempts at genome modification of reproductive cells for clinical application in humans, until the social, environmental, and ethical implications of such operations are broadly discussed among scientific and governmental organizations. </p>
<p>There is no doubt that the exciting and revolutionary CRISPR technology, under the guidance of carefully drafted and broadly accepted rules, will serve well for the well-being of human kind.</p><img src="https://counter.theconversation.com/content/39219/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Shouguang Jin 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>Leading researchers have called for a ban on using a precise gene-editing technology on humans. How can CRISPR advance science and why is it raising concerns?Shouguang Jin, Professor of molecular genetics and microbiology, University of FloridaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/251152014-04-24T05:15:32Z2014-04-24T05:15:32ZGenetic research fights disease but it can be hijacked by politics<figure><img src="https://images.theconversation.com/files/46929/original/rrw8dzhc-1398260142.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Supermodel Gisele Bündchen: sixth generation German, 100% Brazilian.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/bobbekian/5598271601/sizes/l">Bob Bekian</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>There’s a huge variety in physical appearance in Latin America: there are indigenous native Americans, descendants of African slaves, Europeans and Middle Easterners of all kinds, and Chinese and Japanese people – plus all those descended from the mixtures of these native and immigrant groups. </p>
<p>While social scientists are quick to point out that this image of racial tolerance is undermined <a href="http://www.international.ucla.edu/article.asp?parentid=4125">by big problems with racism</a>, biological scientists are interested in Latin American mixture for different reason: genetics. But it’s clear that even between these sciences, a mixing of concepts is also taking place.</p>
<h2>Health of a nation</h2>
<p>Mapping genetic mixture can be helpful in disease research. <a href="http://genepath.med.harvard.edu/%7Ereich/Section%201.htm">Admixture mapping</a>, based on the idea that some health disorders are more common in some populations than others, can be used by scientists to locate <a href="http://www.sanger.ac.uk/about/press/2012/121206-damaging.html">disease-causing genetic variants</a>, often for complex diseases such as diabetes – that may have environmental as well as biological underpinnings. </p>
<p>So when the genomes of patients and healthy people are compared, for example, a high level of European ancestry might indicate where on the genome a particular genetic variant might be found. This can narrow the search down from millions of genetic variants. Admixture mapping uses a limited number of markers to analyse ancestry, so it is cheaper and quicker than studies that scope large areas of the genome.</p>
<p>Geneticists’ main aim is to improve human well-being by locating disease-causing genetic variants. And in the process, they produce a lot of data about human diversity, in Latin America and elsewhere. While you might imagine that this all exists within a neutral space, genetic findings can be used to argue much more than whether whole nations, such as Mexico or Brazil, are <a href="http://www.livescience.com/42278-neanderthal-gene-explains-type-2-diabetes.html">genetically distinctive</a> enough to need specific drug treatments. </p>
<p>To geneticists, the data usually indicate the non-existence of biological races. But to other groups the same data can be used to support existing ideas about racial differences in society.</p>
<h2>Mixing it up</h2>
<p>“Genetic admixture” happens when individuals from two or more previously separated populations come together, and in Latin America this comes from African, Native American and European populations. Numerous genetics studies have analysed the ancestry of local populations, generating vast quantities of data about the diversity of the nation, and there is great genetic diversity between and even within countries. </p>
<p>In Mexico, the government’s National Institute of Genomic Medicine mapped Mexicans’ genomes and showed that all Mexicans had some proportion of all three original populations, though the percentages of ancestries <a href="http://www.pnas.org/content/106/21/8611.abstract">varied from region to region</a>. In Colombia, where most people are mixed, regional diversity is very marked, with particular areas having <a href="http://dx.doi.org/10.1002/ajpa.21270">high levels</a> of African, European or Amerindian ancestry. </p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/46939/original/bjccd6wg-1398268384.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/46939/original/bjccd6wg-1398268384.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=403&fit=crop&dpr=1 600w, https://images.theconversation.com/files/46939/original/bjccd6wg-1398268384.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=403&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/46939/original/bjccd6wg-1398268384.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=403&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/46939/original/bjccd6wg-1398268384.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=507&fit=crop&dpr=1 754w, https://images.theconversation.com/files/46939/original/bjccd6wg-1398268384.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=507&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/46939/original/bjccd6wg-1398268384.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=507&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Quilombolas of Brazil: descendents of Afro-Brazilian slaves.</span>
<span class="attribution"><a class="source" href="http://en.wikipedia.org/wiki/File:Quilombolas.jpg"> Antônio Cruz/ABr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-sa/4.0/">CC BY-NC-SA</a></span>
</figcaption>
</figure>
<p>In Brazil, genetic testing has shown that even white Brazilians carry African and Amerindian ancestry informative markers (AIMs) <a href="http://dx.doi.org/10.1371%2Fjournal.pone.0017063">in their DNA</a>. Differences between regions are also noticeable here: the far south of the country has very European ancestry, because of extensive immigration from countries like Italy and Germany. In contrast the north-east has a lot of African ancestry.</p>
<h2>Reinforcing racial difference</h2>
<p>Geneticists have generally – although not universally – emphasised that the concept of race is not valid in understanding this biological diversity. Although humans vary genetically, most scientists agree it is not possible to divide up that variety into distinct “races”. This is particularly evident in Latin America, because of the history of extensive mixture. Although people in the region may talk about blacks, whites, Indians and <em>mestizos</em> (mixed people), these social categories cannot be defined genetically in a clear way (although this does not stop some people discriminating against others on the basis of their appearance).</p>
<p>Paradoxically, <a href="http://www.socialsciences.manchester.ac.uk/subjects/social-anthropology/our-research/projects/race-genomics-and-mestizaje/">social science research</a> shows that the results of genetic research can have <a href="https://www.dukeupress.edu/Mestizo-Genomics/?viewby=title">the unexpected consequence</a> of reinforcing everyday ideas about racial difference. </p>
<p>Although geneticists dismiss the validity of biological race, they still talk in terms of European, African and Amerindian genetic ancestries in ways that can indicate, to people less versed in genetic science, that as whole populations, these groups are genetically very separate. Genetic studies also present specific populations and regions within Latin America as quite distinctive in terms of their genetic ancestry, which can suggest that, overall, they are genetically very different from each other. </p>
<p>So although it’s a well-known fact that all humans are genetically more than 99% the same, <a href="https://www.dukeupress.edu/Mestizo-Genomics/?viewby=title">genetics can feed into</a> existing popular ideas about racial difference and even exacerbate racism.</p>
<p>In Brazil, for example, there have been heated debates about the rights and wrongs of race-based admissions quotas for black people in some public universities. Those in favour argue that such policies help correct decades of racial injustice, while those against say the quotas just reinforce racial divisions and that social injustice should be tackled with colour-blind reforms. </p>
<p>Some critics of the scheme have used genetic research showing that black people in Brazil have <a href="http://news.bbc.co.uk/1/hi/6284806.stm">substantial amounts of European heritage</a> to argue that there is no “real” black population in Brazil that should benefit from race-based affirmative action policies: all Brazilians are mixed, they say. Defenders of the quotas instead counter that genetics are irrelevant: being black is a social, not a genetic fact. Policemen do not ask for a DNA test before deciding to harass a person who looks black to them.</p>
<p>Genetics don’t exist in a social vacuum. Genetic data may be intended by scientists to simply improve well-being, but the data can also be used – including by the scientists themselves – to support very different positions about human diversity, racial difference and national distinctiveness. </p><img src="https://counter.theconversation.com/content/25115/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Peter Wade received funding from the ESRC (Economic and Social Research Council) and the Leverhulme Trust. He is currently funded by the British Academy and the Wolfson Foundation. He is the author of a number of publications on race and mestizo genomics in Latin America.</span></em></p>There’s a huge variety in physical appearance in Latin America: there are indigenous native Americans, descendants of African slaves, Europeans and Middle Easterners of all kinds, and Chinese and Japanese…Peter Wade, British Academy Wolfson Research Professor in Social Anthropology, University of ManchesterLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/157252013-07-03T04:33:33Z2013-07-03T04:33:33ZMeet mama, papa and mama: how three-parent IVF works<figure><img src="https://images.theconversation.com/files/26761/original/ky37qp8f-1372823641.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Mitochondrial genes are inherited from our mothers’ eggs and passed on through her daughters to subsequent generations.</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>The UK government has announced its <a href="http://www.bionews.org.uk/page_318118.asp">intention to draft proposals</a> allowing carriers of mitochondrial disease to have babies using a controversial IVF treatment that’s currently prohibited. The procedure is controversial because the babies will inherit DNA from three genetic parents.</p>
<p>The draft proposals will detail the regulation of the procedure and need to be endorsed by public consultation and parliament before being put into practice.</p>
<h2>The mighty mitochondria</h2>
<p>Mitochondrial DNA diseases offer distinct challenges to scientists and clinicians because we inherit our mitochondrial DNA in a different manner to our chromosomal genes. Our mitochondrial genes are passed down from our mothers’ eggs and on through her daughters to subsequent generations. </p>
<p>Mitochondrial genes are located in very small bodies called mitochondria and not with the chromosomes in the nucleus of the cell, which determine characteristics such as hair and eye colour.</p>
<p>The mitochondria are the “powerhouses” of the cell as they generate energy. Our cells use this form of energy for their everyday functions; mitochondrial genes are essential to this process. </p>
<p>If one of these genes is mutated, the individual may suffer from very debilitating diseases that affect, for example, muscle and nerve function. There are an increasing number of diseases that are associated with these mutations including diseases we hear about everyday, such as diabetes and Alzheimer’s disease. </p>
<p>The dilemma for a woman who carries mitochondrial DNA disease is that she doesn’t know how much damaged mitochondrial DNA is present in each of her eggs; each of these eggs is likely to have a different amount of mutation. Also, there’s no simple genetic test that can be used to tell the carrier whether her child would be affected. </p>
<p>So, if she and her partner choose to have a family, they will have no idea of the outcome – for them, it’s simply a matter of chance.</p>
<h2>Overcome mitochondrial disease</h2>
<p>Scientists are now developing two approaches to try and prevent children from inheriting these diseases. </p>
<p>The first of these techniques will transfer the mother’s chromosomes from one of her eggs into an egg from a donor. The donor egg would have had its chromosomes removed but retains its healthy mitochondrial DNA. </p>
<p>Then, as with normal IVF treatment, the eggs are fertilised with her partner’s sperm and the resultant embryo can develop for a few days in the lab before being transferred to the chromosomal mother to implant into her womb.</p>
<p>The second technique is similar but would first allow the partner’s sperm to fertilise the egg and then transfer the mother’s and father’s chromosomes to a healthy (empty apart from mitochondria) donor egg.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/26764/original/b5by5ywb-1372824517.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/26764/original/b5by5ywb-1372824517.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/26764/original/b5by5ywb-1372824517.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/26764/original/b5by5ywb-1372824517.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/26764/original/b5by5ywb-1372824517.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/26764/original/b5by5ywb-1372824517.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/26764/original/b5by5ywb-1372824517.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 controversy around these approaches lies with the baby having three genetic parents.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<p>The controversy around these approaches lies with the baby having three genetic parents. These are the chromosomes that the mother and father contribute, as is normal following fertilisation. And then there’s the “third parent” – the mitochondrial DNA mother who donated the egg.</p>
<h2>Some things to consider</h2>
<p>Some groups argue that scientists are entering the brave new world of designer babies and that these techniques are similar to cloning. For them, these procedures are unacceptable.</p>
<p>Others argue that the technologies offer significant benefits, such as the potential to eradicate mitochondrial diseases. </p>
<p>In many respects, UK scientists are at the forefront of convincing government to legalise these procedures under the control of the country’s fertility regulator, the <a href="http://www.hfea.gov.uk/index.html">Human Fertilisation and Embryology Authority</a>.</p>
<p>In the last two years, there have been two significant reports supporting these procedures but they contained important reservations. In 2012, the UK’s <a href="http://www.nuffieldbioethics.org/mitochondrial-dna-disorders">Nuffield Council on Bioethics ruled</a>: </p>
<blockquote>
<p>If further research shows these techniques to be sufficiently safe and effective, we think it would be ethical for families to use them if they wished to, provided they receive an appropriate level of information and support. </p>
</blockquote>
<p>The Human Fertilisation and Embryology Authority sought public views on behalf of the secretary of state for health and <a href="http://www.hfea.gov.uk/7796.html">reported in late March, 2013</a>. It noted: </p>
<blockquote>
<p>… there is general support for permitting mitochondria replacement in the UK, so long as it is safe enough to offer in a treatment setting and is done so within a regulatory framework.</p>
</blockquote>
<p>These reservations are important because they are directed to two key aspects of the procedures. The first is whether any of the mutant mitochondrial DNA accompanies the chromosomes as they are transferred into the donor egg. </p>
<p>This is very important as even a small amount of mutant mitochondrial DNA in the egg can become the dominant population in the baby and lead to mitochondrial disease. We are unsure why this happens but this is currently an area of intense research activity.</p>
<p>The second is whether these techniques would lead to the baby suffering from any harmful side effects.</p>
<p>While I fully embrace these new approaches to fight mitochondrial disease, we still need to make significant advances in determining their safety and effectiveness, and they require a considerable amount of validation. </p>
<p>If they pass these tests, these technologies offer ways to prevent mitochondrial genetic disease from being passed from a female to her descendants through one round of assisted reproduction.</p><img src="https://counter.theconversation.com/content/15725/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Justin St. John receives funding from NHMRC, which looks at mitochondrial mutations and previously held a grant from the UK MRC, which looked at cloned embryos and mitochondrial inheritance. </span></em></p>The UK government has announced its intention to draft proposals allowing carriers of mitochondrial disease to have babies using a controversial IVF treatment that’s currently prohibited. The procedure…Justin St. John, Professor and Director, Centre for Genetic Diseases, Monash Institute of Medical Research, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.