tag:theconversation.com,2011:/au/topics/recombinant-dna-18983/articlesRecombinant DNA – The Conversation2023-07-05T12:23:01Ztag:theconversation.com,2011:article/2060452023-07-05T12:23:01Z2023-07-05T12:23:01Z‘E. coli’ is one of the most widely studied organisms – and that may be a problem for both science and medicine<figure><img src="https://images.theconversation.com/files/534368/original/file-20230627-19-w2lrsx.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2133%2C1404&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">_E. coli_ as a model organism helped researchers better understand how DNA works.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/researcher-with-e-coli-bacteria-royalty-free-image/521677434">Ed Horowitz Photography/The Image Bank via Getty Images</a></span></figcaption></figure><p>In 1857, a young pediatrician named <a href="https://doi.org/10.1038/nrmicro1810">Theodor Escherich</a> discovered what may very well be the most well-studied organism today. The rod-shaped bacterium named <em>Escherichia coli</em>, better known as <em>E. coli</em>, is a very common microbe residing in your gut. It’s also the workhorse of early molecular biology.</p>
<p>Luck likely played a role in its rise in popularity among scientists. Even under 19th-century lab conditions, where sterilization techniques were not perfect and little was known about what food bacteria need to survive, this microbe was easy to cultivate and grow quickly. It can <a href="https://doi.org/10.1098/rspb.2018.0789">replicate in under 20 minutes</a> and can use a variety of <a href="https://doi.org/10.1186/s12918-014-0133-z">carbon sources for energy</a>. </p>
<p>As the first species to have its <a href="https://doi.org/10.1128/jb.29.2.205-213.1935">physiology thoroughly explored</a>, <em>E. coli</em> has contributed fundamental knowledge to the fields of microbiology, molecular genetics and biochemistry, including how DNA replicates, how genes create proteins and how bacteria share genetic material among themselves – a huge <a href="https://theconversation.com/antibiotic-resistance-is-at-a-crisis-point-government-support-for-academia-and-big-pharma-to-find-new-drugs-could-help-defeat-superbugs-169443">cause of antibiotic resistance</a>. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/534417/original/file-20230627-17-qy37yx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram of E. coli structure" src="https://images.theconversation.com/files/534417/original/file-20230627-17-qy37yx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/534417/original/file-20230627-17-qy37yx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=365&fit=crop&dpr=1 600w, https://images.theconversation.com/files/534417/original/file-20230627-17-qy37yx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=365&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/534417/original/file-20230627-17-qy37yx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=365&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/534417/original/file-20230627-17-qy37yx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=458&fit=crop&dpr=1 754w, https://images.theconversation.com/files/534417/original/file-20230627-17-qy37yx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=458&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/534417/original/file-20230627-17-qy37yx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=458&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption"><em>E. coli</em> is a rod-shaped bacterium with flagella that help it move.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/coli-bacteria-micro-biological-vector-royalty-free-illustration/957344970">VectorMine/iStock via Getty Images Plus</a></span>
</figcaption>
</figure>
<p>However, the favored use of <em>E. coli</em> in the lab has also <a href="https://doi.org/10.1529/biophysj.107.104398">led to oversimplifications</a> in the world of microbiology, distracting researchers from the thousands of other bacterial species that <a href="https://doi.org/10.1073/pnas.1707009114">remain understudied</a>. </p>
<p>As <a href="https://doerr.wicmb.cornell.edu/current-lab-members/">microbiologists</a> <a href="https://scholar.google.com/citations?user=yYroRg8AAAAJ&hl=en">studying the</a> inner mechanisms of <a href="https://theconversation.com/looming-behind-antibiotic-resistance-is-another-bacterial-threat-antibiotic-tolerance-200226">antibiotic tolerance</a>, we and colleagues in <a href="https://doerr.wicmb.cornell.edu/">our lab</a> examine bacterial species that physiologically differ from <em>E. coli</em> in hopes of expanding the existing pool of knowledge within microbiology. For instance, drugs like penicillin fall into a class of antibiotics that target the outer defenses of the bacteria. We found that while <em>E. coli</em> succumbs to this attack, species like <em>Vibrio</em> or <em>Klebsiella</em> can <a href="https://theconversation.com/looming-behind-antibiotic-resistance-is-another-bacterial-threat-antibiotic-tolerance-200226">tolerate it and survive</a>. </p>
<p>A one-size-fits-all approach may have worked in the past, but embracing the true diversity of microbes could help scientists better fight the rise of antibiotic resistance.</p>
<h2>Scientific good of <em>E. coli</em></h2>
<p>Researchers worked out the very foundations of life using <em>E. coli</em>. The significance of this bacterium for the field of biology is probably best captured by the biochemist <a href="https://www.nobelprize.org/prizes/medicine/1965/monod/facts/">Jacques Monod</a>, who famously said, “What is true for <em>E. coli</em> is true for the elephant.” </p>
<p>Because researchers were able to watch regions of <a href="https://doi.org/10.1038/158558a0"><em>E. coli</em>‘s DNA become mobile</a>, allowing bacteria to transfer DNA among one another in a process called conjugation, scientists learned to manipulate this process to genetically alter organisms and study the effects of different genes. </p>
<p><em>E. coli</em> helped reveal that <a href="https://doi.org/10.1101/SQB.1963.028.01.011">bacterial chromosomes are circular</a> and that <a href="https://doi.org/10.1016/S0022-2836(59)80045-0">manipulating a specific enzyme</a> can allow scientists to easily clone parts of the bacterial genome. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/534393/original/file-20230627-27-wdxgtr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Microscopy image of E. coli, colored orange" src="https://images.theconversation.com/files/534393/original/file-20230627-27-wdxgtr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/534393/original/file-20230627-27-wdxgtr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=516&fit=crop&dpr=1 600w, https://images.theconversation.com/files/534393/original/file-20230627-27-wdxgtr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=516&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/534393/original/file-20230627-27-wdxgtr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=516&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/534393/original/file-20230627-27-wdxgtr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=648&fit=crop&dpr=1 754w, https://images.theconversation.com/files/534393/original/file-20230627-27-wdxgtr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=648&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/534393/original/file-20230627-27-wdxgtr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=648&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">While <em>E. coli</em> are common residents in your gut, certain strains can cause serious infections.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/coli-sem-royalty-free-image/1414386430">Steve Gschmeissner/Science Photo Library via Getty Images</a></span>
</figcaption>
</figure>
<p><em>E. coli</em> also opened doors to using a type of <a href="https://theconversation.com/viruses-are-both-the-villains-and-heroes-of-life-as-we-know-it-169131">bacterial viruses called phages</a> as an <a href="https://doi.org/10.1085/jgp.22.3.365">alternative to antibiotics</a>. </p>
<p>Widely available knowledge about and methods to study <em>E. coli</em> led to its prominence in academic and commercial research and drug production. In 2015, <a href="https://doi.org/10.4014/jmb.1412.12079">nearly 30% of proteins used as treatments</a> for a wide range of diseases like hepatitis C and multiple sclerosis were derived from <em>E. coli</em>.</p>
<h2>Model organism drawbacks</h2>
<p><em>E. coli</em>’s track record has solidified its place in the lab as a <a href="https://doi.org/10.1007/978-1-4419-9863-7_76">model organism</a>. Model organisms are nonhuman species researchers use to study biology, with the expectation that the findings can be applied to other species like humans. Species are often chosen for their ease of maintenance, quick life cycles and overall cost-effectiveness. </p>
<p>However, model organisms have their drawbacks. Some researchers have argued that drawing parallels across species can <a href="https://theconversation.com/expanding-alzheimers-research-with-primates-could-overcome-the-problem-with-treatments-that-show-promise-in-mice-but-dont-help-humans-188207">sometimes fall short</a>, leading to assumptions about more complex species that may not be true.</p>
<p>Additionally, study findings using nonmodel organisms are often less visible in the broader scientific community, since many researchers focus on organisms with known and defined traits. This bias results in a shadow space where progress is not immediately incorporated into broader scientific knowledge, which can slow down research that actually covers a range from bacteria to elephants.</p>
<h2>ESKAPE pathogens don’t include <em>E. coli</em></h2>
<p>Model organisms are not perfect, and <em>E. coli</em> may not be an effective species to use to study many human bacterial infections. Focusing research on this microbe limits the exploration of how other bacteria infiltrate and infect human hosts. While some <a href="https://doi.org/10.1038/nrmicro818">strains of <em>E. coli</em> can be deadly</a>, they are not the only worrisome pathogens today. </p>
<p><a href="https://doi.org/10.1128/cmr.00181-19">ESKAPE pathogens</a>, a group of bacteria that are highly resistant to antibiotics, pose a massive global health threat because they can quickly evolve traits that allow them to evade immune systems and available treatments. Species within ESKAPE, such as <em>Klebsiella pneumoniae</em> and <em>E. cloacae</em>, are able to resist multiple drugs and <a href="https://doi.org/10.1128/aac.00756-19">exhibit physical characteristics</a> that <em>E. coli</em> does not, such as the ability to remove their cell wall and evade certain drugs.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/EkyAuG9RSSU?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Antibiotic-resistant bacteria are a major global health threat.</span></figcaption>
</figure>
<p>Our lab is studying the unique traits that allow ESKAPE pathogens to survive antibiotics – traits we would not have known about if we used only <em>E. coli</em> as a model organism in our research.</p>
<p>With the many basics of fundamental bacterial cell and molecular biology covered thanks to <em>E. coli</em>, it may be time for researchers to turn toward the new pathogens wreaking havoc on society. Model organisms are wondrous tools, but they have limited power to allow findings to be extrapolated to other organisms. Better understanding the underpinnings of bacterial infections and antibiotics for a given disease requires studying the specific organism.</p><img src="https://counter.theconversation.com/content/206045/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Megan Keller receives funding from National Science Foundation. </span></em></p><p class="fine-print"><em><span>Tobias Dörr receives funding from National Institutes of Health. </span></em></p>Researchers uncovered the foundations of biology by using E. coli as a model organism. But over-reliance on this microbe can lead to knowledge blind spots with implications for antibiotic resistance.Megan Keller, Ph.D. Candidate in Microbiology, Cornell UniversityTobias Dörr, Associate Professor of Microbiology, Cornell UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1933062022-11-15T02:07:36Z2022-11-15T02:07:36Z‘Gain of function’ research can create experimental viruses. In light of COVID, it should be more strictly regulated – or banned<p>The United Nations Environment Programme recently published a <a href="https://wedocs.unep.org/20.500.11822/40871">scientific review</a> that looks at environmental threats and risks in light of the COVID pandemic. It analyses links between human infectious diseases and nature and what we know about how diseases (zoonoses) can transfer from animals to humans. </p>
<p>The report (which I wrote) argues laboratory procedures (including “gain of function” research) should be recognised as one potential driver of zoonotic “spillover”. </p>
<p>The term “gain of function” applies to the functional consequences of changes in the genetic makeup of an organism, including viruses. Such changes can be harmless, or even beneficial. They can occur naturally, when organisms mutate and evolve. </p>
<p>But experiments to deliberately induce mutations are increasingly done in laboratories. In that context, gain of function generally refers to attempts to confer greater transmission and/or virulence to a virus. </p>
<p>Supporters of such research argue it promises to help us be better prepared for pandemics. They <a href="https://www.technologyreview.com/2021/07/26/1030043/gain-of-function-research-coronavirus-ralph-baric-vaccines/">acknowledge</a> risks, but argue these can be managed by the use of <a href="https://www.nature.com/articles/d41586-022-01209-w">highly regulated</a> secure laboratories. Others maintain that the potential risks are simply too high and this type of research should be <a href="https://www.cidrap.umn.edu/news-perspective/2014/06/commentary-case-against-gain-function-experiments-reply-fouchier-kawaoka">banned</a>. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/why-gain-of-function-research-matters-162493">Why gain-of-function research matters</a>
</strong>
</em>
</p>
<hr>
<h2>How DNA discoveries led to ‘gain of function’ research</h2>
<p>During the second world war, DNA (and later RNA) was <a href="https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2001197">identified</a> as the key genetic molecule. DNA’s (and RNA’s) structure provides unique “instructions” for every living organism. </p>
<p>Within just three decades “<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5178364/#:%7E:text=Recombinant%20DNA%20technology%20comprises%20altering,via%20appropriate%20vector%20%5B12%5D">recombinant</a>” technology made it possible to splice together genetic material from different species. Today, this can be done with consummate ease. </p>
<p>Numerous benefits followed, such as the insertion of insulin-producing genes into bacteria. This enabled cheaper, <a href="https://doi.org/10.1186/s12934-014-0141-0">large-scale production</a> of this hormone, essential to treat type I diabetes.</p>
<p>A <a href="https://www.grandviewresearch.com/industry-analysis/biologics-market">2019 report</a> valued the market in therapeutics, mostly arising through recombinant genetic technologies, at more than US$315 billion (A$490 billion). The use of crops genetically engineered to <a href="https://doi.org/10.1104/pp.18.01224">resist disease</a> is also increasing.</p>
<p>However, this type of research also sparked debate and concern.</p>
<p>A key figure in this emerging technology was Paul Berg, a biochemist who shared the 1980 Nobel Prize. Berg’s early work focused on modifying the SV-40 virus, known to be involved in <a href="https://doi.org/10.1016/j.coviro.2012.06.004">tumour growth</a>. Berg abandoned an experiment, inserting SV-40 into a bacterium, for fear, expressed by “<a href="https://www.nobelprize.org/uploads/2018/06/berg-lecture.pdf">many colleagues</a>” that the newly created organism might infect humans, causing cancer.</p>
<p>For the next few decades, scientists navigated the complex ethics and developing technology around gene splicing, under increasingly <a href="https://absa.org/about/hist01/">secure conditions</a> to limit foreseeable biohazard risks.</p>
<h2>Bird flu</h2>
<p>Then, in 2011, researchers performed experiments with a bird flu virus called H5N1. The virus killed an alarming percentage of humans <a href="https://doi.org/10.1073/pnas.1121297109">diagnosed</a> with it. Its saving grace was that it had very poor human-to-human transmission.</p>
<p><a href="https://journals.asm.org/doi/full/10.1128/mbio.00379-12">Controversy</a> arose when two teams of researchers explored and found ways to make H5N1 transmissible between mammals. After first genetically modifying H5N1 researchers performing “serial passage” experiments in a mammalian model (ferrets) to see if they could further adapt it for mammalian to transmission. They succeeded. </p>
<p>Although it wasn’t clear the virus would be as deadly in humans, critics worried this new strain might escape (even from highly secure labs) and cause millions of deaths.</p>
<p>These concerns led US authorities to delay the studies’ full publication and to later <a href="https://doi.org/doi/10.1016/S1473-3099(18)30006-9">restrict funding guidelines</a>. This was intended to reduce genetic experiments perceived as risky.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/494808/original/file-20221111-26-zqux9w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="people in bird market hold up dead ducks" src="https://images.theconversation.com/files/494808/original/file-20221111-26-zqux9w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/494808/original/file-20221111-26-zqux9w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/494808/original/file-20221111-26-zqux9w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/494808/original/file-20221111-26-zqux9w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/494808/original/file-20221111-26-zqux9w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/494808/original/file-20221111-26-zqux9w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/494808/original/file-20221111-26-zqux9w.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">Tests found the H7N9 flu virus in human infections was 99.4% related genetically to that found in live chickens.</span>
<span class="attribution"><a class="source" href="https://photos-cdn.aap.com.au/Image/20130426000686544576?path=/aap_dev14/device/imagearc/2013/04-26/17/1f/35/aapimage-69talo1qnw18vv8ygbb_layout.jpg">AP</a></span>
</figcaption>
</figure>
<h2>Bans imposed, lifted and re-imposed</h2>
<p>A brief, voluntary ban on such research was introduced then lifted in 2012. This type of work was generally called “<a href="https://doi.org/10.1007/s10393-012-0768-4">dual use</a>” because it may be intended for good but could be either <a href="https://www.who.int/news-room/questions-and-answers/item/what-is-dual-use-research-of-concern#:%7E:text=Dual%2Duse%20research%20of%20concern%20(DURC)%20describes%20research%20that,including%20engineering%20and%20information%20technology">misused for harm</a> or inflict harm poorly due to bad luck.</p>
<p>However, lapses in US biosecurity in 2014 strengthened the case for <a href="https://doi.org/10.1016/S1473-3099(18)30006-9">a more careful stance</a>. A US ban on funding for such work was imposed later that year. This time it was not voluntary. Also in 2014, the <a href="http://www.cambridgeworkinggroup.org/">Cambridge Working Group declaration</a> called for a global ban on work that might lead to the creation of “potential pandemic pathogens”. </p>
<p>Supporters of unfettered genetic research continued to insist the benefits outweighed the risks. They also said the risks were manageable if research was conducted in highly secure laboratories. In 2017, the US ban was overturned.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1588123825715044352"}"></div></p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/working-with-dangerous-viruses-sounds-like-trouble-but-heres-what-scientists-learn-from-studying-pathogens-in-secure-labs-161721">Working with dangerous viruses sounds like trouble – but here's what scientists learn from studying pathogens in secure labs</a>
</strong>
</em>
</p>
<hr>
<h2>Now COVID</h2>
<p>Today, COVID has magnified anxiety around this type of genetic research, irrespective of the pandemic’s <a href="https://theconversation.com/the-covid-lab-leak-theory-is-dead-heres-how-we-know-the-virus-came-from-a-wuhan-market-188163">true origin</a>. </p>
<p>In September, the World Health Organization published a <a href="https://www.who.int/publications/i/item/9789240056107">framework</a> to help scientists mitigate biorisks and govern dual-use research of concern. It recognised that gain of function of concern is a real issue, with potentially catastrophic consequences. Global biosecurity expert Raina MacIntyre has discussed these <a href="https://www.mja.com.au/podcast/217/9/mja-podcasts-2022-episode-39-insiders-guide-pandemics-and-biosecurity-prof-raina">concerns</a> recently. </p>
<p>The National Health and Medical Research Council recently completed a <a href="https://www.nhmrc.gov.au/about-us/publications/gain-function-research-review-report#toc__1">review</a> of Australian gain of function research. Such research relies on the integrity of researchers and that all such work must be done in an appropriately safe environment. Approval is also needed from a central authority. </p>
<p>My ongoing <a href="https://doi.org/10.1016/j.soh.2022.100003">work</a> argues we may be nearing a return to an earlier, more cautious approach to biorisks. In our globally connected context, the <a href="https://theintercept.com/2022/11/01/pandemic-1918-flu-virus-biosafety/">potential risks</a> are just too high. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/coronavirus-origins-the-debate-flares-up-but-the-evidence-remains-weak-193143">Coronavirus origins: the debate flares up, but the evidence remains weak</a>
</strong>
</em>
</p>
<hr>
<img src="https://counter.theconversation.com/content/193306/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Colin D. Butler is a member of the Scientific Advisory Committee for Doctors for the Environment, Australia.</span></em></p>Genetic research is big business and has yielded life-saving treatments. But experts are warning of caution about ‘gain of function’ research that has the pandemic potential.Colin D. Butler, Honorary Professor, Australian National UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1746722022-01-19T13:46:08Z2022-01-19T13:46:08ZCORBEVAX, a new patent-free COVID-19 vaccine, could be a pandemic game changer globally<figure><img src="https://images.theconversation.com/files/440522/original/file-20220112-25-tuq2mh.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2191%2C1363&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">CORBEVAX uses recombinant DNA technology that many countries already have the infrastructure to produce.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/global-vaccination-of-planet-earth-royalty-free-illustration/1315224179">Artis777 via iStock/Getty Images Plus</a></span></figcaption></figure><p>The world now has a new COVID-19 vaccine in its arsenal, and at a fraction of the cost per dose.</p>
<p>Two years into the COVID-19 pandemic, the world has seen <a href="https://www.worldometers.info/coronavirus/">over 314 million infections and over 5.5 million deaths worldwide</a>. Approximately <a href="https://www.nytimes.com/interactive/2021/world/covid-vaccinations-tracker.html">60% of the world population</a> has received at least one dose of a COVID-19 vaccine. But there is still a glaring and alarming gap in global access to these vaccines. As a <a href="https://www.rit.edu/ferranlab/maureen-ferran">virologist</a> who has followed this pandemic closely, I contend that this vaccine inequity should be of grave concern to everyone.</p>
<p>If the world has learned anything from this pandemic, it’s that viruses do not need a passport. And yet approximately 77% of people in high- and upper-middle-income countries have received at least one dose of the vaccine – and <a href="https://www.nytimes.com/interactive/2021/world/covid-vaccinations-tracker.html">only 10% in low-income countries</a>. <a href="https://www.washingtonpost.com/world/2021/11/12/coronavirus-vaccine-boosters-global/">Wealthy countries</a> are giving boosters, and even fourth doses, while first and second doses are not available to many worldwide. </p>
<p>But there is hope that a new vaccine called <a href="https://www.texaschildrens.org/texas-children%E2%80%99s-hospital-and-baylor-college-medicine-covid-19-vaccine-technology-secures-emergency">CORBEVAX</a> will help close this vaccination gap.</p>
<h2>How does the CORBEVAX vaccine work?</h2>
<p>All <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/how-they-work.html">COVID-19 vaccines</a> teach the immune system how to recognize the virus and prepare the body to mount an attack. The <a href="https://www.texaschildrens.org/texas-children%E2%80%99s-hospital-and-baylor-college-medicine-covid-19-vaccine-technology-secures-emergency">CORBEVAX vaccine</a> is a <a href="https://www.gavi.org/vaccineswork/what-are-protein-subunit-vaccines-and-how-could-they-be-used-against-covid-19">protein subunit vaccine</a>. It uses a harmless piece of the spike protein from the coronavirus that causes COVID-19 to stimulate and prepare the immune system for future encounters with the virus. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/sVKjEiD6IoM?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Recombinant vaccines commonly use yeast to produce the immune-stimulating proteins of a virus in the lab.</span></figcaption>
</figure>
<p>Unlike the three vaccines approved in the U.S. – <a href="https://theconversation.com/how-do-mrna-vaccines-work-and-why-do-you-need-a-second-dose-5-essential-reads-157198">Pfizer and Moderna’s mRNA vaccines</a> and <a href="https://theconversation.com/how-does-the-johnson-and-johnson-vaccine-compare-to-other-coronavirus-vaccines-4-questions-answered-155944">Johnson & Johnson’s viral vector vaccine</a>, which provide the body instructions on how to produce the spike protein – CORBEVAX delivers the spike protein to the body directly. Like those other approved COVID-19 mRNA vaccines, CORBEVAX also requires <a href="https://timesofindia.indiatimes.com/india/india-approves-corbevax-covovax-vaccines-for-emergency-use/articleshow/88555029.cms">two doses</a>.</p>
<h2>How was CORBEVAX developed?</h2>
<p>CORBEVAX was developed by the co-directors of the <a href="https://www.bcm.edu/departments/pediatrics/divisions-and-centers/tropical-medicine/research/vaccine-development">Texas Children’s Hospital Center for Vaccine Development</a> at Baylor College of Medicine, Drs. <a href="https://www.bcm.edu/people-search/maria-bottazzi-18431">Maria Elena Bottazzi</a> and <a href="https://www.texaschildrens.org/find-a-doctor/peter-jay-hotez-md-phd">Peter Hotez</a>. </p>
<p>During the <a href="https://www.cdc.gov/sars/about/fs-sars.html">2003 SARS outbreak</a>, these researchers created a similar type of vaccine by inserting the genetic information for a portion of the SARS virus spike protein into yeast to produce large amounts of the protein. After isolating the virus spike protein from the yeast and adding an <a href="https://www.thehindu.com/business/biological-e-to-use-dynavaxs-adjuvant-in-corbevax/article35179401.ece">adjuvant</a>, which helps trigger an immune response, the vaccine was ready for use.</p>
<p>The first SARS epidemic was short-lived, and there was little need for Bottazzi and Hotez’s vaccine – until the virus that causes COVID-19, SARS-CoV-2, emerged in 2019. So they dusted off their vaccine and updated the spike protein to match that of SARS-CoV-2, creating the <a href="https://www.texaschildrens.org/texas-children%E2%80%99s-hospital-and-baylor-college-medicine-covid-19-vaccine-technology-secures-emergency">CORBEVAX vaccine</a>. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/UNXJHUnTCxE?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">CORBEVAX received emergency use authorization in India on December 28, 2021.</span></figcaption>
</figure>
<p>Two large clinical trials of <a href="https://www.biologicale.com/news.html">over 3,000 people in India</a> found the vaccine to be safe, well-tolerated and <a href="https://www.texaschildrens.org/texas-children%E2%80%99s-hospital-and-baylor-college-medicine-covid-19-vaccine-technology-secures-emergency">over 90% effective at preventing symptomatic infections</a> from the original strain of COVID-19, and over 80% effective against the delta variant. The vaccine received <a href="https://www.texaschildrens.org/texas-children%E2%80%99s-hospital-and-baylor-college-medicine-covid-19-vaccine-technology-secures-emergency">emergency use authorization</a> in India, and other developing countries are expected to follow.</p>
<p>Interestingly, the group at Baylor was <a href="https://www.npr.org/sections/goatsandsoda/2022/01/05/1070046189/a-texas-team-comes-up-with-a-covid-vaccine-that-could-be-a-global-game-changer">not able to drum up interest or funding in the U.S.</a> for their vaccine. Instead, newer technologies such as mRNA vaccines raced ahead, even though Bottazzi and Hotez’s vaccine design was more advanced, thanks to their <a href="https://www.nbcnews.com/science/science-news/texas-india-patent-free-covid-vaccine-looks-bridge-equity-gaps-rcna10911">previous work during the 2003 SARS and 2012 MERS outbreaks</a>.</p>
<h2>A vaccine built for the world</h2>
<p>Protein subunit vaccines have an advantage over mRNA vaccines in that they can be readily produced using well-established <a href="https://dx.doi.org/10.1016%2Fj.addr.2021.01.001">recombinant DNA technology</a> that is relatively inexpensive and fairly easy to scale up. A similar protein recombinant technology that’s been around for 40 years has been used for the <a href="https://www.who.int/news-room/feature-stories/detail/the-novavax-vaccine-against-covid-19-what-you-need-to-know">Novavax COVID-19 vaccine</a>, which is <a href="https://www.cnbc.com/2022/01/10/novavax-ceo-covid-vaccine-could-be-cleared-in-multiple-countries-soon.html">available for use in 170 countries</a>, and the <a href="https://www.nature.com/articles/d42859-020-00016-5">recombinant hepatitis B vaccine</a>.</p>
<p>This vaccine can be produced at a much larger scale because <a href="https://www.nbcnews.com/science/science-news/texas-india-patent-free-covid-vaccine-looks-bridge-equity-gaps-rcna10911">appropriate manufacturing facilities are already available</a>. Also key to global access is that CORBEVAX can be <a href="https://economictimes.indiatimes.com/industry/healthcare/biotech/healthcare/new-protein-based-covid-vaccine-doesnt-need-cold-storage-study/articleshow/87580913.cms">stored in a regular refrigerator</a>. Therefore, it is possible to produce millions of doses rapidly and distribute them relatively easily. In comparison, <a href="https://www.nytimes.com/interactive/2021/health/pfizer-coronavirus-vaccine.html">producing mRNA vaccines</a> is more expensive and complicated because they are based on newer technologies, rely on highly skilled workers and often require <a href="https://www.technologynetworks.com/biopharma/articles/covid-19-vaccine-storage-and-stability-349023">ultralow temperatures</a> for storage and transport.</p>
<p>Another major difference is that the CORBEVAX vaccine was developed with <a href="https://www.advancedsciencenews.com/corbevax-vaccine-offers-solution-to-global-vaccine-inequity/">global vaccine access in mind</a>. The goal was to make a low-cost, easy-to-produce and -transport vaccine using a well-tested and safe method. Key to this, the researchers were <a href="https://www.nbcnews.com/science/science-news/texas-india-patent-free-covid-vaccine-looks-bridge-equity-gaps-rcna10911">not concerned with intellectual property or financial benefit</a>. The vaccine was produced without significant public funding; the <a href="https://www.nbcnews.com/science/science-news/texas-india-patent-free-covid-vaccine-looks-bridge-equity-gaps-rcna10911">US$7 million</a> needed for development was provided by philanthropists. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/440919/original/file-20220114-30-1l4ut2k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Woman holding child gets vaccinated by a health care worker in India." src="https://images.theconversation.com/files/440919/original/file-20220114-30-1l4ut2k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/440919/original/file-20220114-30-1l4ut2k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/440919/original/file-20220114-30-1l4ut2k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/440919/original/file-20220114-30-1l4ut2k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/440919/original/file-20220114-30-1l4ut2k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/440919/original/file-20220114-30-1l4ut2k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/440919/original/file-20220114-30-1l4ut2k.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">India is the first country to grant emergency use authorization to CORBEVAX.</span>
<span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/VirusOutbreakIndiaVaccination/a7d7130831b6471ca08c028908d84745">Anupam Nath/AP</a></span>
</figcaption>
</figure>
<p>COBREVAX is currently <a href="https://www.advancedsciencenews.com/corbevax-vaccine-offers-solution-to-global-vaccine-inequity/">licensed patent-free</a> to Biological E. Limited (BioE), India’s largest vaccine maker, which plans to manufacture <a href="https://www.scientificamerican.com/article/a-covid-vaccine-for-all/">at least 100 million doses per month starting in February 2022</a>. This patent-free arrangement means that other low- and middle-income countries can produce and distribute this cheap, stable and relatively easy-to-scale vaccine locally.</p>
<p>Combined, this means that CORBEVAX is <a href="https://www.axios.com/india-authorizes-covid-vaccines-corbevax-novavax-795a5b7e-d9b7-4e8f-a1ec-bdaba5c5b13b.html">one of the cheapest vaccines currently available</a>. How well it works against the <a href="https://www.scientificamerican.com/article/a-covid-vaccine-for-all/">omicron variant</a> is under investigation. However, the CORBEVAX story can be <a href="https://www.nbcnews.com/science/science-news/texas-india-patent-free-covid-vaccine-looks-bridge-equity-gaps-rcna10911">used as a model</a> to address vaccine inequity when it is necessary to vaccinate the world population – against COVID-19 and other diseases on the horizon.</p>
<h2>The necessity of vaccine equity</h2>
<p>There are many reasons <a href="https://www.cgdev.org/debate/would-exempting-covid-19-vaccines-intellectual-property-rights-improve-global-access">global access to vaccines is inequitable</a>. For example, the governments of wealthy nations purchase vaccines in advance, which limits supply. While developing countries do have vaccine production capacity, low- and middle-income countries in Africa, Asia and Latin America still need to be able to afford the cost of placing orders.</p>
<p>The Indian government has ordered <a href="https://www.healio.com/news/infectious-disease/20220105/qa-unpatented-covid19-vaccine-could-finally-vaccinate-the-world">300 million doses of CORBEVAX, and BioE plans to produce more than 1 billion shots</a> for people in developing countries. For context, the U.S. and other G7 nations have pledged to donate <a href="https://launchandscalefaster.org/covid-19/vaccinedonations">over 1.3 billion doses of COVID vaccines, yet only 591 million doses have been shipped</a>. These numbers mean that if BioE is able to produce 1.3 billion doses of CORBEVAX as planned, this vaccine will <a href="https://www.healio.com/news/infectious-disease/20220105/qa-unpatented-covid19-vaccine-could-finally-vaccinate-the-world">reach more people than those vaccinated by what’s been donated and shipped by the wealthiest nations</a>.</p>
<p>[<em>Over 140,000 readers rely on The Conversation’s newsletters to understand the world.</em> <a href="https://memberservices.theconversation.com/newsletters/?source=inline-140ksignup">Sign up today</a>.]</p>
<p>As the <a href="https://www.cdc.gov/coronavirus/2019-ncov/variants/omicron-variant.html">omicron variant</a> has shown, new variants can spread across the world quickly and are much more likely to <a href="https://www.healthline.com/health-news/unvaccinated-people-are-increasing-the-chances-for-more-coronavirus-variants-heres-how">develop in unvaccinated people</a> and <a href="https://www.msn.com/en-us/health/medical/expect-more-worrisome-variants-after-omicron-scientists-say/ar-AASOna4?li=BBnb7Kz">continue to emerge</a> as long as global vaccination rates remain low. It is <a href="https://www.theguardian.com/world/2022/jan/12/repeated-covid-boosters-not-viable-strategy-against-new-variants-who-experts-warn">unlikely that boosters</a> will end this pandemic. Rather, developing globally accessible vaccines like CORBEVAX represent an important first step in vaccinating the world and ending this pandemic.</p>
<p><em>Article updated to indicate percentage of people in low- and upper-middle to high income countries who have received at least one vaccine dose. Article also updated to note that clinical trials were performed in India and include more information on effectiveness against different strains.</em></p><img src="https://counter.theconversation.com/content/174672/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Maureen Ferran receives funding from The National Institutes of Health.</span></em></p>CORBEVAX is anticipated to significantly expand vaccine access to people in low- and middle-income countries.Maureen Ferran, Associate Professor of Biology, Rochester Institute of TechnologyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/682442016-11-13T07:00:33Z2016-11-13T07:00:33ZHow biotechnology could offer hope for snakebite victims<figure><img src="https://images.theconversation.com/files/144546/original/image-20161104-25329-m9kg8g.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The black mamba is one of the most notorious venomous snakes in the world.</span> <span class="attribution"><a class="source" href="https://c2.staticflickr.com/6/5556/14707823092_fc246dc441_b.jpg">Flickr</a></span></figcaption></figure><p>Snakebite is a major public health burden for low-income countries in tropical parts of the world. There are around <a href="http://www.snakebiteinitiative.org/?page_id=577">5 million bites and 150,000 deaths</a> every year. And about <a href="https://www.msf.org.za/about-us/publications/briefing-documents/snakebite-how-public-health-emergency-slithered-under-radar">400,000 victims become permanently disabled</a> annually.</p>
<p>In Africa, the most notorious of snake species is the black mamba (<em>Dendroaspis polylepis</em>). It is feared for its <a href="http://www.sciencedirect.com/science/article/pii/S1874391915000561">potent rapid-acting venom</a> and its characteristic feature of typically striking more than once. The problem is that it always injects venom in its bite. So a bite from this species has an almost 100% fatality rate if left untreated. Other venomous African snake species that pose a danger to humans include other mambas, cobras, puff adders, boomslangs, and a range of vipers.</p>
<p>Treatment against snakebite venom is currently limited to antiserum derived from animals. There have been incremental innovations in the manufacture of antivenoms. But most are still produced using <a href="http://www.who.int/bloodproducts/snake_antivenoms/snakeantivenomguideline.pdf">methods developed 120 years ago</a>. Current antivenom production involves immunising animals, like horses or sheep, with venom milked from snakes and then isolating antibodies from the serum. The process is expensive and labour intensive.</p>
<p>A combination of these factors and a difficult market environment has some led commercial producers <a href="http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0001670">to withdraw</a>. As a result, current stocks of functional antivenom will <a href="http://www.nature.com/news/vipers-mambas-and-taipans-the-escalating-health-crisis-over-snakebites-1.20495">soon expire</a>. The situation is so bad that experts and NGOs active in the field refer to the lack of antivenom – particularly in sub-Saharan Africa – as <a href="http://www.nature.com/news/africa-braced-for-snakebite-crisis-1.18357">a neglected health crisis</a>.</p>
<p>But there is hope on the horizon. Innovations in biotechnology being used to produce pharmaceuticals for other treatments could also be applied to producing antivenoms. These would be made in laboratory conditions rather than extracted from animals.</p>
<p>We have been exploring various avenues to produce antivenoms based on mixtures of antibodies, rather than having them derive from animals. This is a scientifically and commercially sound opportunity that promises to bring the shortage of snakebite antivenoms in sub-Saharan Africa to an end, not immediately but certainly in the medium to longer term.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/144548/original/image-20161104-25322-wxr379.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/144548/original/image-20161104-25322-wxr379.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=613&fit=crop&dpr=1 600w, https://images.theconversation.com/files/144548/original/image-20161104-25322-wxr379.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=613&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/144548/original/image-20161104-25322-wxr379.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=613&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/144548/original/image-20161104-25322-wxr379.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=771&fit=crop&dpr=1 754w, https://images.theconversation.com/files/144548/original/image-20161104-25322-wxr379.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=771&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/144548/original/image-20161104-25322-wxr379.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=771&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Schematic representation of serum-based antivenom production.</span>
<span class="attribution"><span class="source">Andreas Hougaard Laustsen</span></span>
</figcaption>
</figure>
<h2>What biotechnology can deliver</h2>
<p>Innovations in biotechnology can make antivenoms more cost-effective and easier to produce. They can also be made more effective against snakebites. Alternative avenues, already established within biotechnology, could be pursued to create novel ones. These have the potential to improve treatment against snakebite and lower cost of production. Lower manufacturing costs would make it profitable for pharmaceutical companies to bring low cost antivenoms to the market. It could even provide a financial incentive for antivenom manufacturers to distribute antivenoms to rural parts of the tropics.</p>
<p>One established method that could be adapted is the use of DNA immunisation techniques. This would do away with laborious venom extractions. This technique would involve immunising horses <a href="http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0030184">with toxin-encoding DNA</a>, inducing immunisation (similar to the effect that venom itself provides). This technique has been investigated in various animal models and may enable venom-independent antivenom manufacture <a href="https://www.researchgate.net/publication/268810231_Developing_Snake_Antivenom_Sera_by_Genetic_Immunization_A_Review">in the future</a>. </p>
<p>But we are following a different avenue. We are pursuing the replacement of the active components (antibodies) in the animal-derived antivenom with <a href="https://www.researchgate.net/publication/308249085_Recombinant_Antivenoms">recombinant human versions</a> – antivenoms produced by cell cultivation in biotechnological production systems. This method, producing pharmaceutical products through cell cultivation <a href="http://www.diabetesforecast.org/2013/jul/making-insulin.html">in fermentation tanks</a>, has been developed and perfected over the last 30 years. It’s been used to produce a range of pharmaceutical products like blood factors and human hormones such as insulin. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/144549/original/image-20161104-25362-kwu41t.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/144549/original/image-20161104-25362-kwu41t.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=502&fit=crop&dpr=1 600w, https://images.theconversation.com/files/144549/original/image-20161104-25362-kwu41t.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=502&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/144549/original/image-20161104-25362-kwu41t.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=502&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/144549/original/image-20161104-25362-kwu41t.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=631&fit=crop&dpr=1 754w, https://images.theconversation.com/files/144549/original/image-20161104-25362-kwu41t.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=631&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/144549/original/image-20161104-25362-kwu41t.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=631&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Schematic representation of two strategies for the manufacture of oligoclonal antibody mixtures by cell cultivation.</span>
<span class="attribution"><span class="source">Andreas Hougaard Laustsen</span></span>
</figcaption>
</figure>
<p>Future recombinant antivenoms could be based on mixtures of human antibodies. These antivenoms would be more compatible with the human immune system, limiting the incidence of adverse reactions. The concept has seen success in <a href="http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature13777.html?utm_content=bufferb2c23&utm_medium=social&utm_source=twitter.com&utm_campaign=buffer#affil-auth">ZMapp, a medication used to fight Ebola</a> and therapies involving oncology based <a href="http://www.symphogen.com/pipeline">antibody mixtures</a>.</p>
<h2>Costing</h2>
<p>A recombinant antivenom would also be more effective. This is because current antivenoms contain a large fraction of therapeutically irrelevant antibodies. These are generated by animals’ immune systems to fight a range of bacteria and viruses. A recombinant antivenom, based on a mixture of human antibodies, would be designed in a way that the antibodies would be specifically selected to target the most relevant toxins in snake venom. Therapeutically irrelevant antibodies not targeting snake toxins would be absent. </p>
<p>But, wouldn’t this be exorbitantly <a href="http://www.nature.com/news/vipers-mambas-and-taipans-the-escalating-health-crisis-over-snakebites-1.20495">expensive?</a> Not at all. Our estimates show that recombinant antivenoms would be a <a href="http://www.nature.com/nature/journal/v538/n7623/full/538041e.html">cost-effective solution</a> to the snakebite crisis. They could be used to treat an average snakebite case in Africa for $30-$150 per treatment compared with the current cost of well <a href="http://www.reuters.com/article/us-uk-snake-venom-idUSKBN0MT2F320150402">over $500</a>. </p>
<p>Recombinant antivenoms are still under development. They are unlikely to be on the market for about a decade. More focus and resources are needed to accelerate the discovery and testing of toxin-targeting antibodies of human origin. We hope our efforts will help catalyse this process and shorten the time in which more effective – and less expensive – antivenoms reach clinics.</p><img src="https://counter.theconversation.com/content/68244/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andreas Hougaard Laustsen receives funding from the Novo Nordisk Foundation (NNF16OC0019248).</span></em></p><p class="fine-print"><em><span>Mikael Engmark receives funding from The Novo Nordisk Foundation (NNF13OC0005613)</span></em></p>One way to tackle the snakebite antivenom crisis may be through biotechnological innovation to make antivenoms more cost-effective, easier to produce, and more efficacious against snakebites.Andreas Hougaard Laustsen, Postdoctoral Fellow at the Department of Biotechnology and Biomedicine, Technical University of DenmarkMikael Engmark, PhD Student Department of Bio and Health Informatics, Technical University of DenmarkLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/606742016-07-27T21:20:13Z2016-07-27T21:20:13ZGMOs lead the fight against Zika, Ebola and the next unknown pandemic<figure><img src="https://images.theconversation.com/files/132228/original/image-20160727-21595-158l7x3.jpg?ixlib=rb-1.1.0&rect=0%2C646%2C5748%2C4122&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">GMOs may very well have filled up that syringe.</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-336640973/stock-photo-hand-with-a-syringe-injection-vaccination-medicine-pop-art-retro-style.html?src=pp-same_artist-346093292-5N0wHCvzYAJ7L24IKgcP_g-2&ws=1">Syringe image via www.shutterstock.com</a></span></figcaption></figure><p>The shadow of the Zika virus hangs over the Rio Olympic Games, with visitors and even <a href="http://www.telegraph.co.uk/sport/0/rio-olympics-which-athletes-have-withdrawn-over-zika-fears/">high-profile athletes citing worries</a> about Zika as a reason to stay away (even if the <a href="https://theconversation.com/the-olympics-wont-spread-zika-around-the-world-62822">risk is probably quite low</a>). The public’s concerns are a striking example of the need to rapidly combat emerging infectious diseases.</p>
<p>In the fight against <a href="https://www.cdc.gov/zika/">Zika</a>, public health experts have turned to what may sound like an unlikely ally: genetically modified organisms, or <a href="http://gmo.geneticliteracyproject.org/FAQ/what-are-gmos/">GMOs</a>.</p>
<p>Consumers are used to hearing about GMOs in food crops, but may be unaware of the vital role GMOs play in medicine. Most modern biomedical advances, especially the vaccines used to eradicate disease and protect against pandemics such as Zika, <a href="https://www.cdc.gov/vhf/ebola/">Ebola</a> and the <a href="http://www.flu.gov">flu</a>, rely on the same molecular biology tools that are used to create genetically modified organisms. To protect the public, scientists have embraced GMO technology to quickly study new health threats, manufacture enough protective vaccines, and monitor and even predict new outbreaks. </p>
<h2>Vaccines, meet molecular biology</h2>
<p>Vaccines work with the immune system to strengthen the body’s own natural defenses. A vaccine offers a preview of a potential infection, so the immune system is ready to pounce if the real threat shows up. </p>
<p>The earliest vaccines were primitive – think Edward Jenner in the 1790s <a href="http://www.jennermuseum.com/vaccination.html">inoculating against smallpox</a> by rubbing together the open wounds of uninfected patients and those with cowpox. But over the years, advances in medical technology led to improved vaccines. The modern age of vaccines was ushered in by the introduction of <a href="http://www.jove.com/science-education-database/2/basic-methods-in-cellular-and-molecular-biology">molecular biology tools</a> in the 1970s, which vastly improved our ability to study and manipulate viruses.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/132067/original/image-20160726-7058-1k9brj6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/132067/original/image-20160726-7058-1k9brj6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/132067/original/image-20160726-7058-1k9brj6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=513&fit=crop&dpr=1 600w, https://images.theconversation.com/files/132067/original/image-20160726-7058-1k9brj6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=513&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/132067/original/image-20160726-7058-1k9brj6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=513&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/132067/original/image-20160726-7058-1k9brj6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=644&fit=crop&dpr=1 754w, https://images.theconversation.com/files/132067/original/image-20160726-7058-1k9brj6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=644&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/132067/original/image-20160726-7058-1k9brj6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=644&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Viruses have spikes for attaching to host cells and a cargo bay to hold its genes (red).</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic.mhtml?id=387259318">Virus illustration via www.shutterstock.com.</a></span>
</figcaption>
</figure>
<p>Under the microscope, viruses look like spiky balls, with an internal cargo bay that houses their genetic material. “Dissecting” a virus means using molecular biology tools to study its genes (whether encoded via DNA or RNA) up close. For example, researchers can “cut and paste” genes to study them in isolation and figure out what they do. Or researchers can cause genetic mutations and watch how an organism responds.</p>
<p>When DNA is modified or studied inside different cells than those from which it originated, it is called “<a href="https://www.britannica.com/science/recombinant-DNA-technology">recombinant DNA</a>.” An organism with recombinant DNA is considered a GMO.</p>
<p>GMO developers use molecular biology, manipulating genes to study and alter plant DNA, for instance, to create new varieties that can thrive with <a href="https://www.geneticliteracyproject.org/wp-content/uploads/2013/07/Biotechnology-infographic_7.29.13-clean.pdf">less water or fewer pesticides</a>.</p>
<p>For vaccine researchers, molecular biology is a jack-of-all-trades. These tools allow scientists to figure out the keys to a virus’ survival by dissecting its DNA, devise new vaccines, manufacture those vaccines cheaply and quickly, and monitor which viruses in the wild might become public health headaches. According to <a href="http://medschool.umaryland.edu/FACULTYRESEARCHPROFILE/viewprofile.aspx?id=25096">Dr. José Esparza</a>, president of the <a href="http://gvn.org/">Global Virus Network</a> and professor at University of Maryland Medical School, “It is impossible to do research in biomedicine without doing molecular biology.”</p>
<h2>GMOs advance science of vaccines</h2>
<p>One disease currently being addressed with the help of molecular biology is <a href="http://www.who.int/mediacentre/factsheets/fs204/en/">hepatitis B</a>, which kills one person every minute worldwide – even though we do have an effective vaccine.</p>
<p>In the 1960s, virologists realized that the hepatitis B antigen – a protein from the virus’ outer shell that triggers an immune response in an infected person – showed up in the blood of hepatitis B patients. To their surprise, injecting a healthy person with the purified antigen protected against future infections. The first hepatitis B vaccine (<a href="http://www.nasonline.org/publications/beyond-discovery/hepatitis-b-story.pdf">HBV</a>), approved in 1981, was made by harvesting the antigen from the blood of hepatitis B carriers, including intravenous drug users.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/132201/original/image-20160727-21591-273uhb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/132201/original/image-20160727-21591-273uhb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/132201/original/image-20160727-21591-273uhb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/132201/original/image-20160727-21591-273uhb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/132201/original/image-20160727-21591-273uhb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/132201/original/image-20160727-21591-273uhb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/132201/original/image-20160727-21591-273uhb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/132201/original/image-20160727-21591-273uhb.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">Administering the hepatitis B vaccine to a child at a rural health center in India.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/unitednationsdevelopmentprogramme/4968223306">United Nations Development Programme</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<p>Once recombinant DNA technology was developed, researchers could isolate the gene for the virus’ antigen protein, allowing for HBV to be manufactured in laboratories via those genetic instructions instead of from infected blood. Currently, both FDA-approved <a href="https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/appdx-full-b.pdf">vaccines for hepatitis B</a> include the recombinant version of the antigen. </p>
<p>And molecular biology can be used to accelerate the development of new vaccines. For example, in late June, a “<a href="https://www.statnews.com/2016/06/20/zika-vaccine-inovio/">DNA vaccine</a>” was the first to be approved for human trials against the Zika virus. Rather than containing the Zika antigen itself, the vaccine contains a gene for the Zika antigen which the patient’s body then produces.</p>
<p>The announcement of this breakthrough came less than five months after the World Health Organization declared Zika a “<a href="http://www.who.int/mediacentre/news/statements/2016/emergency-committee-zika-microcephaly/en/">public health emergency of international concern</a>.” Without the tools to modify and isolate sections of DNA, Dr. Esparza of the Global Virus Network notes, “we would not be able to do this with the necessary speed and efficiency.”</p>
<h2>GMOs as pharma factories</h2>
<p>Consumers who scrupulously avoid genetically modified foods might be surprised to know that lots of <a href="https://gmoanswers.com/studies/gmos-food-and-medicine-overview">drugs and vaccines</a> they rely on are the product of GMOs.</p>
<p>Many vaccines and top-grossing pharmaceuticals contain proteins as the main ingredient. Proteins are <a href="http://dx.doi.org/10.3389/fmicb.2014.00172">too costly</a> and delicate to manufacture from scratch. But living cells must make proteins to survive, and they can be coaxed to produce medical proteins in bulk, requiring little more than the DNA instructions and sugary broth as fuel. Since these genetic blueprints must be inserted into the cells, many vaccines and drugs are technically the product of GMOs. </p>
<p>Modified bacteria, yeast and even <a href="https://biotechhistory.org/magazine-article/vital-tools-brief-history-cho-cells/">Chinese hamster cells</a> are the unheralded molecular factories of the drug and vaccine industry. In 2014, 10 of the <a href="http://cellculturedish.com/2015/03/10-biologics-on-best-selling-drugs-list-for-2014/">top 25 best-selling drugs</a> were “<a href="http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CBER/ucm133077.htm">biologics</a>” – drugs made up of recombinantly produced proteins – including blockbuster treatments for arthritis, cancer and diabetes. Of the 10 vaccines that the <a href="https://www.cdc.gov/vaccines/parents/downloads/parent-ver-sch-0-6yrs.pdf">Centers for Disease Control and Prevention (CDC) recommends</a> for newborns, three are available in recombinant form; HBV, for example, is produced by modified yeast. The earliest recombinant vaccines and drugs have been in use for <a href="http://www.biotechnology.amgen.com/timeline.html">three decades</a>. </p>
<p>Perhaps the most dramatic example of GMO use in medicine came during the 2014 Ebola outbreak in West Africa. When American doctor Kent Brantly and other Western volunteers contracted Ebola, several were cured by a “<a href="http://wgntv.com/2014/08/04/secret-serum-likely-saved-ebola-patients/">secret serum</a>” called <a href="http://doi.org/10.1038/nature13777">Zmapp</a>. Manufactured by <a href="http://www.fastcompany.com/3045741/most-creative-people-2015/meet-ebolas-soft-spoken-plant-loving-arch-nemesis">genetically modified tobacco plants</a>, it’s a mixture of several proteins that attack the Ebola virus.</p>
<p>The technology for producing drugs in genetically modified plants, dubbed “pharming,” was developed by <a href="https://sols.asu.edu/people/charles-arntzen">Charles Arntzen</a> in the early 1990s. In the case of Zmapp, the antibodies are made in the tobacco plant’s leaves. When they’re harvested, rather than being made into cigarettes, their cells are popped open and the drug is collected. Researchers call pharming “<a href="http://www.fastcompany.com/3045741/most-creative-people-2015/meet-ebolas-soft-spoken-plant-loving-arch-nemesis">a revolution for the field</a>” of manufacturing pharmaceuticals.</p>
<p>The biotech company <a href="http://www.appliedbiotech.org">Applied Biotechnology Institute</a> has embraced the technique to make a next-generation pharmed vaccine. They’re developing a genetically modified corn plant that produces the hepatitis B antigen. The plant could be harvested and turned into an oral vaccine tablet, which looks like a small wafer, as opposed to a liquid which must be refrigerated and injected. The hope is that an oral vaccine can lower the rates of hepatitis B in the developing world, where the cold supply chain, sanitary needles and trained medical personnel the current vaccine depends on are either lacking or prohibitively expensive.</p>
<h2>Future of diagnostics</h2>
<p>Beyond improved vaccines, equally pressing for the future of public health will be addressing pandemics that have not yet even begun. Virologist Esparza counts 11 pandemics that have occurred in the last 14 years, including Ebola, the <a href="http://www.flu.gov/about_the_flu/h1n1/">H1N1 (swine) flu</a> and <a href="https://www.cdc.gov/coronavirus/mers/">MERS</a> – all but one of which were viruses. “It is totally predictable there will be other pandemics. What is not easy to predict is which one. Two years ago, no one could have predicted Zika,” he told me.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/132267/original/image-20160727-21578-1cb427x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/132267/original/image-20160727-21578-1cb427x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/132267/original/image-20160727-21578-1cb427x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/132267/original/image-20160727-21578-1cb427x.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/132267/original/image-20160727-21578-1cb427x.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/132267/original/image-20160727-21578-1cb427x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/132267/original/image-20160727-21578-1cb427x.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/132267/original/image-20160727-21578-1cb427x.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">Molecular biology technology has made possible simple diagnostic tools, like this paper-based test for Zika. Areas that have turned purple indicate samples infected with the virus.</span>
<span class="attribution"><span class="source">Wyss Institute at Harvard University</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>Molecular biology is often found on the front lines of pandemics, appearing in on-the-spot diagnostic tools that are cheap and do not require extensive equipment or training. For example, a Harvard-led team <a href="http://dx.doi.org/10.1016/j.cell.2016.04.059">recently unveiled</a> a <a href="http://www.forbes.com/sites/jenniferhicks/2016/05/09/researchers-develop-low-cost-paper-diagnostic-test-for-zika-virus/#24ee99f53fb4">paper-based test</a> – similar to a pregnancy test – that uses the <a href="https://theconversation.com/crispr-cas-gene-editing-technique-holds-great-promise-but-research-moratorium-makes-sense-pending-further-study-43371">CRISPR/Cas</a> gene editing tool to distinguish the Zika virus from the closely related <a href="https://www.statnews.com/2016/02/17/zika-dengue-infections/">Dengue virus</a>. If the Cas9 protein encounters the specific DNA sequence of Zika virus in a drop of blood, it starts a chain reaction that results in a colored readout.</p>
<p>Beyond diagnosing single patients, molecular biology tools will be used to get ahead of the as-yet-unknown pandemic threats that lie in the future. Public health officials are <a href="http://www.who.int/csr/alertresponse/en/">calling for monitoring infections</a> in the places where new diseases frequently emerge. Quick and accurate diagnostic tests are key to determining which viruses are already circulating and would allow researchers to anticipate new pandemics and develop and stockpile vaccines. </p>
<p>“Until now, we have had a very reactive response” to threats like Zika and Ebola, says Dr. Esparza. With the help of GMOs, infectious disease experts have the tools to get ahead of the next outbreak, moving beyond reaction to quick detection, containment and even prevention.</p><img src="https://counter.theconversation.com/content/60674/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jeff Bessen works in a molecular biology lab that has received funding on various projects from the NIH, HHMI, and DARPA. The lab has received funding from Monsanto for a project unrelated to vaccines and medicines.
</span></em></p>Public health experts enlist the molecular biology tools that create genetically modified organisms – as well as the GMOs themselves – in the fight against emerging infectious diseases.Jeff Bessen, Ph.D. Candidate in Chemical Biology, Harvard UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/514802015-12-01T19:15:45Z2015-12-01T19:15:45ZWhy we can trust scientists with the power of new gene-editing technology<figure><img src="https://images.theconversation.com/files/103829/original/image-20151201-26546-ofjsvn.png?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Gene editing allows us to eliminate any misspellings, introduce beneficial natural variants, or perhaps cut out or insert new genes. </span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/libertasacademica/7016004213/">Libertas Academica/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p><a href="http://www.nationalacademies.org/gene-editing/index.htm">A summit of experts</a> from around the world is meeting in Washington to consider the scientific, ethical and governance issues linked to research into gene editing. Convened in response to recent advances in the field, the summit includes experts from the US National Academy of Science, the UK’s Royal Society and the Chinese Academy of Science. </p>
<p><a href="https://theconversation.com/explainer-what-is-genome-editing-25072">Gene editing</a> is a new technique that allows one to change chosen genes at will. It has been applied to many organisms but <a href="http://www.ncbi.nlm.nih.gov/pubmed/25894090">a recent report</a> from China showing the modification of human embryos using a technology known as <a href="https://theconversation.com/explainer-crispr-technology-brings-precise-genetic-editing-and-raises-ethical-questions-39219">CRISPR/Cas9</a> mediated editing set alarm bells ringing. </p>
<p>Here’s the main fear: if you modify an embryo (and therefore also its germline), you change not only the person that embryo will become but also its future sons, daughters, grandsons and granddaughters. </p>
<p>Since we don’t know much about this technology, it’s right to stop and think about it. But personally I’m not overly concerned: we’ve been here – or somewhere quite like it – before. </p>
<h2>Learning from history</h2>
<p>In 1975, scientists met at Asilomar on the Californian coast to discuss a moratorium on recombinant DNA (that’s DNA formed from combining constituents from different organisms). </p>
<p>Alarm bells had started ringing when scientists realised they could combine the DNA from a monkey virus with a circle of DNA called a plasmid, carrying an antibiotic resistance gene purified from the human gut bacteria, <em>Escherichia coli</em> (<a href="http://www.about-ecoli.com/"><em>E. coli</em></a>). </p>
<p>This cocktail sounded dangerous and scientists discussed a voluntary moratorium on certain experiments, as well as sensible guidelines for containing recombinant material within laboratories. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/103830/original/image-20151201-26578-1n37bah.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/103830/original/image-20151201-26578-1n37bah.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/103830/original/image-20151201-26578-1n37bah.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/103830/original/image-20151201-26578-1n37bah.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/103830/original/image-20151201-26578-1n37bah.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/103830/original/image-20151201-26578-1n37bah.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/103830/original/image-20151201-26578-1n37bah.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Horizontal gene transfer occurs in nature when DNA is carried between species by viruses and related carriers.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/blprnt/3694704325/">Jer Thorp/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Regulations and guidelines are still in place and after 40 years few, if anyone, has been harmed by recombinant DNA. And there have been no reported outbreaks of recombinant material that have significantly affected human health or the environment. </p>
<p>All technologies, including different agricultural practices, have upsides and downsides, and most medicines and treatments have side effects. But recombinant DNA would now have to be classed among the least dangerous of scientific developments.</p>
<h2>Understanding science</h2>
<p>One reason the technology has proven so safe may be that genetic recombination has been going on for millions of years. In most cases, genes are simply passed on from parent to child. But horizontal gene transfer also occurs in nature when DNA is carried between organisms or even species by viruses. </p>
<p>Over time, DNA is naturally swapped around and moved. Though you may have eaten transgenic plant products, I very much doubt you’ve noticed.</p>
<p>There was a fear “mad scientists” would invent dangerous new superbugs and killer viruses. Perhaps this could have happened, but sadly there are enough pre-existing dangerous substances and naturally occurring diseases, which have been perfected by evolution, out there already. So germ warfare scientists are more likely to just use them.</p>
<p>Another fear was that researchers would modify humans. Most countries quickly outlawed the modification of human germ cells and, to my knowledge, it has never occurred. In general, scientists seem to have obeyed the regulations. </p>
<p>But another reason is that it has proved difficult to introduce new genes into mammalian cells. It’s legal to modify human cells, such as blood stem cells, to cure genetic diseases. But human cells are among the hardest to modify. Human “anti-viral” software seems so powerful that it inhibits the stable insertion and expression of new DNA.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/103831/original/image-20151201-26595-n1zvf7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/103831/original/image-20151201-26595-n1zvf7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=426&fit=crop&dpr=1 600w, https://images.theconversation.com/files/103831/original/image-20151201-26595-n1zvf7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=426&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/103831/original/image-20151201-26595-n1zvf7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=426&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/103831/original/image-20151201-26595-n1zvf7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=536&fit=crop&dpr=1 754w, https://images.theconversation.com/files/103831/original/image-20151201-26595-n1zvf7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=536&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/103831/original/image-20151201-26595-n1zvf7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=536&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Fears that ‘mad scientists’ would use recombinant DNA techonolgy to create superbugs like MRSA have not eventuated.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/umdnews/8161119599/in/photolist-draSwB-bhhrmR-ibEmCY-6VESwi-kGq5r8-4BwtJZ-4BAEnC-4BACiY-pBtfyG-cNTZNU-cNTZH1-cPsbUS-nVzYss-cPsc4Y-cPsbTm-cPsc1u-dV5XkT-csnK1o-csnJwo-csnJzY-csnJum-crj1db-dMgueE-5QXCmd-dMaV1V-ddaJBA-r4TfX3-csnJBs-f37psU-csnJKy-csnJG1-f3SzQs-dNZC2S-7bepH7-2Mxz5W-dNZBuf-csnJLU-csnJXj-ekEQAg-csnJNm-csnJHY-7biLPL-dNZBwm-edsrB8-e29y8j-dZtRxo-dZo9rR-dZo9bv-dZtQGW-dZtQhf">Merrill College of Journalism Press Releases</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<h2>The promise of gene editing</h2>
<p>I’m sure you’ve met people who’ve had their teeth straightened or undergone cosmetic surgery. But you’ve probably never met anyone who’s had gene therapy or ever seen a transgenic animal.</p>
<p>Could that change with gene editing? Gene editing is so precise that one doesn’t just lob in a new gene and hope it works; what one does is edit the existing gene to eliminate any misspellings, introduce beneficial natural variants, or perhaps cut out or insert new genes into chosen locations. </p>
<p>Our anti-viral software may not even detect what’s happened. And provided there aren’t any “off-target’” effects, where we hit the wrong gene, there may be no or minimal side effects.</p>
<p>Now that’s it’s so easy to meddle in human genes, why shouldn’t we worry? </p>
<p>The new technology is a game-changer – but it’s not a runaway phenomenon, like releasing cane toads, blackberries or rabbits into Australia. After 40 years, there have been few, if any problems, with genetically modified organisms. And the experiments - though much easier now - are still so elaborate and expensive that the technology will spread slowly. </p>
<p>We’ll likely remain cautious about modifying human embryos and about any modification that may be passed on to the next generation. To date, consent is required for all treatments. And while patients may opt for experimental cancer therapy or surgery, we always try to think carefully when others, who cannot consent, will be affected.</p>
<p>Some people will even ask why it’s wrong to correct a defect that could haunt future generations. Or, if we could introduce a gene variant that protects people from cancer – such as creating a duplication of the <a href="http://www.ncbi.nlm.nih.gov/books/NBK22268/">tumour suppressor gene p53</a> – why wouldn’t we want that for our children?</p>
<p>Genetics is a branch of science that’s ripe for discussions, and conversations on recombinant DNA, gene therapy, cloning and stem cells have all gone well. Guidelines have been sensible and researchers have largely complied with them. </p>
<p>The very fact that people from across the world are gathering to discuss the issues surrounding the latest breakthroughs in gene technology is a very strong sign that the science will be used responsibly. One hopes that the concurrent meeting on climate change in Paris is also a victory for science.</p><img src="https://counter.theconversation.com/content/51480/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Merlin Crossley works for the University of New South Wales. He receives funding from the National Health and Medical Research Council and the Australian Research Council. He is a Trustee of the Australian Museum, a Board Member of the Sydney Institute of Marine Science, a Council Member of the European Molecular Biology Laboratory Australia, and the Australian Science Media Centre.</span></em></p>Should the gathering of experts from around the world that’s considering the scientific, ethical, and governance issues linked to research into gene editing ring alarm bells?Merlin Crossley, Dean of Science and Professor of Molecular Biology, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/433712015-07-29T10:21:09Z2015-07-29T10:21:09ZCRISPR/Cas gene-editing technique holds great promise, but research moratorium makes sense pending further study<figure><img src="https://images.theconversation.com/files/89724/original/image-20150726-8461-st71yb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The red Cas9 nuclease protein uses a blue guide RNA sequence to cut yellow DNA at a complementary site.</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-213287815/stock-photo-crispr-cas-gene-editing-complex-from-streptococcus-pyogenes-the-cas-nuclease-protein-uses-a.html">CRISPR-Cas9 via www.shutterstock.com</a></span></figcaption></figure><p>CRISPR/Cas is a new technology that allows unprecedented control over the DNA code. It’s sparked a revolution in the fields of genetics and cell biology, becoming the scientific equivalent of a household name by raising hopes about new ways to cure diseases including cancer and to unlock the remaining mysteries of our cells.</p>
<p>The gene editing technique also raises concerns. Could the new tools allow parents to order “designer babies”? Could premature use in patients lead to unforeseen and potentially dangerous consequences? This potential for abuse or misuse led prominent scientists to <a href="http://dx.doi.org/10.1126/science.aab1028">call for a halt</a> on some types of new research until ethical issues can be discussed – a voluntary ban that was <a href="http://www.nature.com/news/chinese-scientists-genetically-modify-human-embryos-1.17378">swiftly ignored</a> in some quarters.</p>
<p>The moratorium is a positive step toward preserving the public’s trust and safety, while the promising new technology can be further studied.</p>
<h2>Editing DNA to cure disease</h2>
<p>While most human <a href="http://www.nature.com/scitable/topic/genes-and-disease-17">diseases</a> are caused, at least partially, by mutations in our DNA, current therapies treat the symptoms of these mutations but not the genetic root cause. For example, <a href="http://www.mayoclinic.org/diseases-conditions/cystic-fibrosis/basics/definition/con-20013731">cystic fibrosis</a>, which causes the lungs to fill with excess mucus, is caused by a single DNA mutation. However, cystic fibrosis treatments focus on the symptoms – working to reduce mucus in the lungs and fight off infections – rather than correcting the mutation itself. That’s because making precise changes to the three-billion-letter DNA code remains a challenge even in a Petri dish, and it is unprecedented in living patients. (The only current example of gene therapy, called <a href="http://www.uniqure.com/products/glybera/">Glybera</a>, does not involve modifying the patient’s DNA, and has been approved for limited use in Europe to treat patients with a <a href="http://www.nlm.nih.gov/medlineplus/ency/article/000408.htm">digestive disorder</a>.)</p>
<p>That all changed in 2012, when <a href="http://rna.berkeley.edu/">several</a> <a href="http://arep.med.harvard.edu/">research</a> <a href="http://zlab.mit.edu/">groups</a> demonstrated that a DNA-cutting technology called <a href="http://www.nytimes.com/2014/03/04/health/a-powerful-new-way-to-edit-dna.html?_r=0">CRISPR/Cas</a> could operate on human DNA. Compared to previous, inefficient methods for editing DNA, CRISPR/Cas offers a shortcut. It acts like a pair of DNA scissors that cut where prompted by a special strand of RNA (a close chemical relative of DNA). Snipping DNA turns on the cell’s DNA repair process, which can be hijacked to either disable a gene – say, one that allows tumor cells to grow uncontrollably – or to fix a broken gene, such as the mutation that causes cystic fibrosis. The advantages of the Cas9 system over its predecessor genome-editing technologies – its <a href="http://link.springer.com/article/10.1007%2Fs40484-014-0030-x">high specificity</a> and the ease of navigating to a specific DNA sequence with the “guide RNA” – have contributed to its rapid adoption in the scientific community.</p>
<p>The barrier to fixing the DNA of diseased cells appears to have evaporated. </p>
<h2>Playing with fire</h2>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/89726/original/image-20150726-8446-1uic8j6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/89726/original/image-20150726-8446-1uic8j6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/89726/original/image-20150726-8446-1uic8j6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/89726/original/image-20150726-8446-1uic8j6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/89726/original/image-20150726-8446-1uic8j6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/89726/original/image-20150726-8446-1uic8j6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/89726/original/image-20150726-8446-1uic8j6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/89726/original/image-20150726-8446-1uic8j6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Just the baby I ordered?</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/jar0d/10194703106">Sander van der Wel</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>With the advance of this technique, the obstacles to altering genes in embryos are falling away, opening the door to so-called “designer babies” with altered appearance or intelligence. Ethicists have long feared the <a href="http://www.technologyreview.com/featuredstory/535661/engineering-the-perfect-baby/">consequences</a> of allowing parents to choose the traits of their babies. Further, there is a wide gap between our understanding of disease and the genes that might cause them. Even if we were capable of performing flawless genetic surgery, we don’t yet know how specific changes to the DNA will manifest in a living human. Finally, the editing of germ line cells such as embryos could permanently introduce altered DNA into the gene pool to be inherited by descendants.</p>
<p>And making cuts in one’s DNA is not without risks. Cas9 – the scissor protein – is known to cleave DNA at <a href="https://www.genomeweb.com/sequencing-technology/new-sequencing-methods-reveal-target-effects-crisprcas9">unintended</a> or “off-target” sites in the genome. Were Cas9 to inappropriately chop an important gene and inactivate it, the therapy could cause cancer instead of curing it. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/89727/original/image-20150726-8478-58yrxx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/89727/original/image-20150726-8478-58yrxx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/89727/original/image-20150726-8478-58yrxx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/89727/original/image-20150726-8478-58yrxx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/89727/original/image-20150726-8478-58yrxx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/89727/original/image-20150726-8478-58yrxx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/89727/original/image-20150726-8478-58yrxx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/89727/original/image-20150726-8478-58yrxx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Not so fast….</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/fazen/489667079">Stefano Mortellaro</a>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<h2>Take it slow</h2>
<p>All the concerns around Cas9 triggered a very unusual event: a call from prominent scientists to halt some of this research. In March of 2015, a group of researchers and lawyers <a href="http://dx.doi.org/10.1126/science.aab1028">called for</a> a voluntary pause on further using CRISPR technology in germ line cells until ethical guidelines could be decided.</p>
<p>Writing in the journal Science, the group – including two <a href="http://www.nobelprize.org/nobel_prizes/medicine/laureates/1975/baltimore-bio.html">Nobel</a> <a href="http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1980/berg-bio.html">laureates</a> and the inventors of the CRISPR technology – noted that we don’t yet understand enough about the link between our health and our DNA sequence. Even if a perfectly accurate DNA-editing system existed – and Cas9 surely doesn’t yet qualify – it would still be premature to treat patients with genetic surgery. The authors disavowed genome editing only in specific cell types such as embryos, while encouraging the basic research that would put future therapeutic editing on a firmer foundation of evidence.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/89725/original/image-20150726-8461-7343pa.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/89725/original/image-20150726-8461-7343pa.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/89725/original/image-20150726-8461-7343pa.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/89725/original/image-20150726-8461-7343pa.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/89725/original/image-20150726-8461-7343pa.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/89725/original/image-20150726-8461-7343pa.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/89725/original/image-20150726-8461-7343pa.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/89725/original/image-20150726-8461-7343pa.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The basic research isn’t ready for deployment in human embryos yet.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-19115449/stock-photo-cancer-research.html">Petri dishes image via www.shutterstock.com</a></span>
</figcaption>
</figure>
<h2>Pushing ahead</h2>
<p>Despite this call for CRISPR/Cas research to be halted, a Chinese research group <a href="http://dx.doi.org/10.1007/s13238-015-0153-5">reported</a> on their attempts at editing human embryos only two months later. Described in the journal Protein & Cell, the authors treated nonviable embryos to fix a gene mutation that causes a blood disease called <a href="http://ghr.nlm.nih.gov/condition/beta-thalassemia">β-thalassemia</a>.</p>
<p>The study results proved the concerns of the Science group to be well-founded. The treatment killed nearly one in five embryos, and only half of the surviving cells had their DNA modified. Of the cells that were even modified, only a fraction had the disease mutation repaired. The study also revealed off-target DNA cutting and incomplete editing among all the cells of a single embryo. Obviously these kinds of errors are problematic in embryos meant to mature into fully grown human beings.</p>
<p>George Daley, a Harvard biologist and member of the group that called for the moratorium, <a href="http://dx.doi.org/10.1038/nature.2015.17378">concluded that</a> “their study should be a stern warning to any practitioner who thinks the technology is ready for testing to eradicate disease genes.” </p>
<p>In the enthusiasm and hype surrounding Cas9, it is easy to forget that the technology has been in wide use for barely three years.</p>
<h2>Role of a moratorium</h2>
<p>Despite the publication of the Protein & Cell study – whose experiments likely took place at least months earlier – the Science plea for a moratorium can already be considered a success. The request from such a respected group has brought visibility to the topic and put pressure on universities, regulatory boards and the editors of scientific journals to discourage such research. (As evidence of this pressure, the Chinese authors were <a href="http://www.reuters.com/article/2015/04/23/us-science-embryos-idUSKBN0NE2A320150423">rejected</a> from at least two top science journals before getting their paper accepted.) And the response to the voluntary ban has thus far not included accusations of “stifling academic freedom,” possibly due to the scientific credibility of the organizers.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/89728/original/image-20150726-8453-b1qrae.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/89728/original/image-20150726-8453-b1qrae.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/89728/original/image-20150726-8453-b1qrae.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=741&fit=crop&dpr=1 600w, https://images.theconversation.com/files/89728/original/image-20150726-8453-b1qrae.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=741&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/89728/original/image-20150726-8453-b1qrae.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=741&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/89728/original/image-20150726-8453-b1qrae.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=931&fit=crop&dpr=1 754w, https://images.theconversation.com/files/89728/original/image-20150726-8453-b1qrae.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=931&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/89728/original/image-20150726-8453-b1qrae.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=931&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Recombinant DNA researcher Paul Berg organized the conference and later shared the Nobel Prize in chemistry. He also signed the call to slow CRISPR research.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Paul_Berg_in_1980.jpg">National Library of Medicine</a></span>
</figcaption>
</figure>
<p>While rare, the call for a moratorium on research for ethical reasons can be traced to an earlier controversy over DNA technology. In 1975, a group that came to be known as the <a href="http://dx.doi.org/10.1073/pnas.72.6.1981">Asilomar Conference</a> called for caution with an emerging technology called recombinant DNA until its safety could be evaluated and ethical guidelines could be published. The similarity between the two approaches is no coincidence: several authors of the Science essay were also members of the Asilomar team.</p>
<p>The Asilomar guidelines are now <a href="http://www.the-scientist.com/?articles.view/articleNo/12781/title/The-Asilomar-Process--Is-It-Valid-/">widely viewed</a> as having been a proportionate and responsible measure, placing the right emphasis on safety and ethics without hampering research progress. It turns out recombinant DNA technology was much less dangerous than originally feared; existing evidence already shows that we might not be so lucky with Cas9. Another important legacy of the Asilomar conference was the promotion of an open discussion involving experts as well as the general public. By heeding the lessons of caution and public engagement, hopefully the saga of CRISPR/Cas will unfold in a similarly responsible – yet exciting – way.</p><img src="https://counter.theconversation.com/content/43371/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jeff Bessen receives funding from the NIH and DARPA for research into genome editing technologies, including Cas9.</span></em></p>Until more is understood, it’s sensible to limit experimentation that would make changes to germ line cells that would be passed on to future generations.Jeff Bessen, PhD Candidate in Chemical Biology, Harvard UniversityLicensed as Creative Commons – attribution, no derivatives.