tag:theconversation.com,2011:/fr/topics/nanobiology-30214/articlesNanobiology – The Conversation2020-01-19T18:59:43Ztag:theconversation.com,2011:article/1299802020-01-19T18:59:43Z2020-01-19T18:59:43ZNot bot, not beast: scientists create first ever living, programmable organism<p>A remarkable combination of artificial intelligence (AI) and biology has produced the world’s first “living robots”. </p>
<p>This week, a research team of roboticists and scientists <a href="https://www.pnas.org/content/early/2020/01/07/1910837117">published</a> their recipe for making a new lifeform called xenobots from stem cells. The term “xeno” comes from the frog cells (<em>Xenopus laevis</em>) used to make them.</p>
<p>One of the researchers <a href="https://www.forbes.com/sites/simonchandler/2020/01/14/worlds-first-living-robot-invites-new-opportunities-and-risks/#379ef46c3caf">described the creation</a> as “neither a traditional robot nor a known species of animal”, but a “new class of artifact: a living, programmable organism”. </p>
<p>Xenobots are less than 1mm long and made of 500-1000 living cells. They have various simple shapes, including some with squat “legs”. They can propel themselves in linear or circular directions, join together to act collectively, and move small objects. Using their own cellular energy, they can live up to 10 days.</p>
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<figcaption><span class="caption">This time-lapse video shows cells being manipulated and assembled to create xenobots. (Original video: Douglas Blackiston, Tufts University)</span></figcaption>
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<p>While these “reconfigurable biomachines” could vastly improve human, animal, and environmental health, they raise legal and ethical concerns.</p>
<h2>Strange new ‘creature’</h2>
<p>To make xenobots, the research team used a supercomputer to test thousands of random designs of simple living things that could perform certain tasks.</p>
<p>The computer was programmed with an AI “evolutionary algorithm” to predict which organisms would likely display useful tasks, such as moving towards a target. </p>
<p>After the selection of the most promising designs, the scientists attempted to replicate the virtual models with frog skin or heart cells, which were manually joined using microsurgery tools. The heart cells in these bespoke assemblies contract and relax, giving the organisms motion.</p>
<p>The creation of xenobots is groundbreaking.</p>
<p>Despite being described as “programmable living robots”, they are actually completely organic and made of living tissue. The term “robot” has been used because xenobots can be configured into different forms and shapes, and “programmed” to target certain objects – which they then unwittingly seek.</p>
<p>They can also repair themselves after being damaged. </p>
<h2>Possible applications</h2>
<p>Xenobots may have great value.</p>
<p><a href="https://www.technologyreview.com/f/615041/these-xenobots-are-living-machines-designed-by-an-evolutionary-algorithm/">Some speculate</a> they could be used to clean our polluted oceans by collecting microplastics.</p>
<p>Similarly, they may be used to enter confined or dangerous areas to scavenge toxins or radioactive materials.</p>
<p>Xenobots designed with carefully shaped “pouches” might be able to carry drugs into human bodies.</p>
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Read more:
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<p>Future versions may be built from a patient’s own cells to repair tissue or target cancers. Being biodegradable, xenobots would have an edge on technologies made of plastic or metal.</p>
<p>Further development of biological “robots” could accelerate our understanding of living and robotic systems. Life is incredibly complex, so manipulating living things could reveal some of life’s mysteries — and improve our use of AI.</p>
<h2>Legal and ethical questions</h2>
<p>Conversely, xenobots raise legal and ethical concerns. In the same way they could help target cancers, they could also be used to hijack life functions for malevolent purposes.</p>
<p>Some argue artificially making living things is unnatural, hubristic, or involves “playing God”.</p>
<p>A more compelling concern is that of unintended or malicious use, as we have seen with technologies in fields including nuclear physics, chemistry, biology and AI. </p>
<p>For instance, xenobots might be used for hostile biological purposes prohibited under international law. </p>
<p>More advanced future xenobots, especially ones that live longer and reproduce, could potentially “malfunction” and go rogue, and out-compete other species.</p>
<p>For complex tasks, xenobots may need sensory and nervous systems, possibly resulting in their sentience. A sentient programmed organism would raise additional ethical questions. Last year, the revival of a disembodied pig brain <a href="https://www.nature.com/articles/d41586-019-01216-4">elicited concerns about different species’ suffering</a>.</p>
<h2>Managing risks</h2>
<p>The xenobot’s creators have rightly acknowledged the need for discussion around the ethics of their creation.</p>
<p>The 2018 scandal over using CRISPR (which allows the introduction of genes into an organism) may provide an instructive lesson <a href="https://www.technologyreview.com/s/614761/nature-jama-rejected-he-jiankui-crispr-baby-lulu-nana-paper/">here</a>. While the experiment’s goal was to reduce the susceptibility of twin baby girls to HIV-AIDS, associated risks caused ethical dismay. The scientist in question <a href="https://www.theguardian.com/world/2019/dec/30/gene-editing-chinese-scientist-he-jiankui-jailed-three-years">is in prison</a>.</p>
<p>When CRISPR became widely available, some experts called for a <a href="https://www.theguardian.com/science/2019/mar/13/scientists-call-for-global-moratorium-on-crispr-gene-editing">moratorium</a> on heritable genome editing. Others <a href="https://www.liebertpub.com/doi/10.1089/crispr.2019.0016?utm_source=miragenews&utm_medium=miragenews&utm_campaign=news&">argued</a> the benefits outweighed the risks. </p>
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Read more:
<a href="https://theconversation.com/chinas-failed-gene-edited-baby-experiment-proves-were-not-ready-for-human-embryo-modification-128454">China's failed gene-edited baby experiment proves we're not ready for human embryo modification</a>
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<p>While each new technology should be considered impartially and based on its merits, giving life to xenobots raises certain significant questions: </p>
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<li>Should xenobots have biological kill-switches in case they go rogue?</li>
<li>Who should decide who can access and control them?</li>
<li>What if “homemade” xenobots become possible? Should there be a moratorium until regulatory frameworks are established? How much regulation is required? </li>
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<p>Lessons learned in the past from advances in other areas of science could help manage future risks, while reaping the possible benefits.</p>
<h2>Long road here, long road ahead</h2>
<p>The creation of xenobots had various biological and robotic precedents. Genetic engineering has created genetically modified mice that become <a href="http://www.understandinganimalresearch.org.uk/news/research-medical-benefits/glowing-mice/">fluorescent</a> in UV light. </p>
<p><a href="https://advances.sciencemag.org/content/1/4/e1500077">Designer microbes</a> can produce drugs and food ingredients that may eventually <a href="https://solarfoods.fi/">replace animal agriculture</a>. </p>
<p>In 2012, scientists created an <a href="https://blogs.scientificamerican.com/brainwaves/what-would-it-take-to-really-build-an-artificial-jellyfish">artificial jellyfish</a> called a “medusoid” from rat cells.</p>
<p>Robotics is also flourishing. </p>
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<a href="https://images.theconversation.com/files/310613/original/file-20200117-118352-15ylufw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/310613/original/file-20200117-118352-15ylufw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/310613/original/file-20200117-118352-15ylufw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/310613/original/file-20200117-118352-15ylufw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/310613/original/file-20200117-118352-15ylufw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/310613/original/file-20200117-118352-15ylufw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/310613/original/file-20200117-118352-15ylufw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/310613/original/file-20200117-118352-15ylufw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Nanobots are tiny robots that carry out specific tasks. In medicine, they can be used for targeted drug delivery.</span>
<span class="attribution"><span class="source">shutterstock</span></span>
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<p>Nanobots can <a href="http://news.mit.edu/2013/nanotechnology-could-help-fight-diabetes-0516">monitor people’s blood sugar levels</a> and may eventually be able to <a href="https://www.smithsonianmag.com/innovation/tiny-robots-can-clear-clogged-arteries-180955774/">clear clogged arteries</a>. </p>
<p>Robots can incorporate living matter, which we witnessed when engineers and biologists created a <a href="https://www.sciencemag.org/news/2016/07/robotic-stingray-powered-light-activated-muscle-cells">sting-ray robot</a> powered by light-activated cells.</p>
<p>In the coming years, we are sure to see more creations like xenobots that evoke both wonder and due concern. And when we do, it is important we remain both open-minded and critical.</p><img src="https://counter.theconversation.com/content/129980/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Xenobots have been called the world’s first “living robots”. They are made entirely of living tissue, and can be programmed to move towards a certain object.Simon Coghlan, Senior Research Fellow in Digital Ethics, School of Computing and Information Systems, The University of MelbourneKobi Leins, Senior Research Fellow in Digital Ethics, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/886852017-12-13T23:31:30Z2017-12-13T23:31:30ZDesigner proteins that package genetic material could help deliver gene therapy<figure><img src="https://images.theconversation.com/files/197877/original/file-20171205-31063-15cffwi.jpg?ixlib=rb-1.1.0&rect=70%2C19%2C3305%2C2753&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Delivering genetic material is a key challenge in gene therapy.</span> <span class="attribution"><a class="source" href="https://www.freepik.com/free-photos-vectors/invitation">Invitation image created by Kstudio</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>If you’ve ever bought a new iPhone, you’ve experienced good packaging.</p>
<p>The way the lid slowly separates from the box. The pull tab that helps you remove the device. Even the texture of the paper inserts matters to Apple. Every aspect of iPhone packaging has been <a href="https://gizmodo.com/5879097/apple-packing-is-so-good-because-they-employ-a-dedicated-box-opener">meticulously designed</a> for a pleasing aesthetic experience.</p>
<p>When it comes to genome editing, good packaging is even more crucial.</p>
<p>In a recent article in the journal Nature, a team of bioengineers here at the University of Washington describe a new type of packaging <a href="https://doi.org/10.1038/nature25157">built to protect genetic material</a>, specifically RNA. This designer packaging consists of proteins which self-assemble into soccer ball-like nanostructures known as capsids. These tiny particles encapsulate RNA, allowing it to move around the bodies of mice for hours without being degraded — sidestepping one of the biggest challenges to successful gene editing.</p>
<h2>Delivering genetic material</h2>
<p>Moving genetic material (DNA or RNA) throughout the body – or targeting it into specific organs and tissues – is a key challenge in human genome editing. In addition to <a href="https://theconversation.com/beyond-just-promise-crispr-is-delivering-in-the-lab-today-77596">technology like CRISPR</a>, which physically cuts DNA, some potentially lifesaving gene therapies will require the <a href="https://doi.org/10.1016/j.tibtech.2015.02.011">insertion of new genetic elements</a> to serve as templates for repair. But these genetic blueprints face perilous conditions once they enter the body.</p>
<p>Because deadly infections often start when unwanted genetic material from a pathogen makes it into our cells, our bodies have evolved sophisticated ways of quickly <a href="https://doi.org/10.1038/nsmb.1744">detecting and demolishing foreign DNA and RNA molecules</a>. Simply put: Unprotected genetic material doesn’t stick around for very long. In fact, CRISPR itself evolved in bacteria to perform <a href="https://doi.org/10.1126/science.1179555">precisely this search-and-destroy function</a> before it was co-opted by scientists as a gene-editing tool.</p>
<p>Biotechnologists have known about this delivery problem for some time. Most researchers have turned to what might sound like a surprising solution: engineered viruses.</p>
<p>Viruses contain their own genetic material which they insert or inject to infect a cell. If viruses can be redesigned to instead transmit human-specified genetic material into the cells of patients without also making them sick, <a href="http://dx.doi.org/10.1038/mt.2015.164">the thinking goes</a>, then perhaps they could serve as the physical packaging for new therapeutic bits of DNA or RNA.</p>
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<span class="caption">Current gene therapy trial participants are injected with billions of copies of a corrective gene encased in a modified virus.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Genetic-Frontiers-Gene-Editing/3d637f0a90c94083b7d35b058798c220/1/0">AP Photo/Eric Risberg</a></span>
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<p>The most popular virus for delivering molecules into human cells at present is the <a href="https://doi.org/10.1038/nrg3742">adeno-associated virus</a>, or AAV. Not only is this virus a darling of laboratory research, the Food and Drug Administration is <a href="http://www.sciencemag.org/news/2017/10/fda-experts-offer-unanimous-endorsement-pioneering-gene-therapy-blindness">poised to approve</a> a pioneering gene therapy which employs it after recent clinical trials revealed engineered AAVs could help <a href="https://doi.org/10.1016/S0140-6736(17)31868-8">safely restore limited sight to the blind</a>. But, <a href="https://doi.org/10.1038/nrg1066">experts note</a>, this benign virus is not a perfect solution to the gene delivery problem.</p>
<h2>A virus-free solution</h2>
<p>Using a repurposed virus to deliver a custom genetic payload is a bit like using a repurposed box to deliver a new iPhone. It can work, but it may not give the best results. The goods can arrive damaged or not at all, and repurposed viruses can also <a href="https://doi.org/10.1038/nrg1066">inflame the immune system</a>. Researchers are still trying to figure out how to tweak them so they behave in safe and predictable ways.</p>
<p>Rather than starting with a complex, difficult-to-modify virus, my colleagues here at the <a href="http://www.ipd.uw.edu/">Institute for Protein Design</a> began their work with a relatively simple designer protein capsid. This empty vessel did not yet hold any RNA.</p>
<p>The team used computer-guided protein design and artificial laboratory evolution to create a suitable encapsulating structure. They were able to produce one nanostructure that engulfs RNA blueprints at a rate <a href="http://dx.doi.org/10.1016/S1525-0016(02)00019-9">comparable to the best engineered AAVs</a>.</p>
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<span class="caption">Both of these tiny, soccer ball-like structures package genetic material. On the left, a natural virus. On the right, a computer-generated capsid (which cannot replicate). A thousand billion billion copies of either one could fit inside a real soccer ball.</span>
<span class="attribution"><span class="source">Ian Haydon</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
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<p>To begin, they modified the interior surface of a <a href="https://doi.org/10.1038/nature18010">computer-designed capsid</a> so that RNA could stick to it. This got some genetic material inside but didn’t afford it much protection. By mutating this version of the capsid in the laboratory and picking out the best performing mutants, they were able to hone in on new versions which packaged even more RNA, protected it, and persisted inside mouse blood (a hostile environment for foreign RNA and proteins).</p>
<p>In other words, the team made use of one of nature’s favorite strategies: evolution.</p>
<p>“We were surprised it worked so well, to be honest,” said Gabe Butterfield, a lead author of <a href="https://doi.org/10.1038/nature25157">the study</a>. “Evolution was able to hit upon a small number of mutations that made large improvements in complex properties [like persisting in mouse blood].”</p>
<h2>Toward gene therapy</h2>
<p>Marc Lajoie, another lead author, is optimistic about the future of these designer capsids, but thinks they are “pretty far away” from use in patients.</p>
<p>“We certainly have plenty of work ahead of us,” said Lajoie. But with this two-pronged approach that combines viruses’ capacity to evolve with modern biotech’s abilities to design synthetic nanomaterials, they have their long-term sights set on engineering molecules that “deliver diverse cargos [ranging] from small molecule drugs to nucleic acids to proteins” within human bodies.</p>
<p>With smartphones, well-designed packaging plays a supporting aesthetic role. But if gene therapy is to become a fixture of medicine in the 21st century, innovative packaging may be essential.</p><img src="https://counter.theconversation.com/content/88685/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ian Haydon is a graduate student at the University of Washington's Institute for Protein Design. </span></em></p>One big challenge for gene therapies is delivering DNA or RNA safely to cells inside patients’ bodies. New nanoparticles could be an improvement over the current standard – repurposed viruses.Ian Haydon, Doctoral Student in Biochemistry, University of WashingtonLicensed as Creative Commons – attribution, no derivatives.