tag:theconversation.com,2011:/ca/topics/chimeras-35489/articlesChimeras – The Conversation2023-09-17T20:00:27Ztag:theconversation.com,2011:article/2133572023-09-17T20:00:27Z2023-09-17T20:00:27ZPigs with human brain cells and biological chips: how lab-grown hybrid lifeforms bamboozle scientific ethics<figure><img src="https://images.theconversation.com/files/548449/original/file-20230915-27-7uzm4i.jpeg?ixlib=rb-1.1.0&rect=44%2C74%2C4947%2C3667&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/early-stage-embryo-stem-cell-research-387281866">Shutterstock</a></span></figcaption></figure><p>Earlier this month, scientists at the Guangzhou Institutes of Biomedicine and Health <a href="https://www.sciencedaily.com/releases/2023/09/230907130350.htm">announced</a> they had successfully grown “humanised” kidneys inside pig embryos.</p>
<p>The scientists genetically altered the embryos to remove their ability to grow a kidney, then injected them with human stem cells. The embryos were then implanted into a sow and allowed to develop for up to 28 days.</p>
<p>The resulting embryos were made up mostly of pig cells (although some human cells were found throughout their bodies, including in the brain). However, the embryonic kidneys were largely human. </p>
<p>This breakthrough suggests it may soon be possible to generate human organs inside part-human “chimeric” animals. Such animals could be used for medical research or to grow organs for transplant, which could save many human lives.</p>
<p>But the research is ethically fraught. We might want to do things to these creatures we would never do to a human, like kill them for body parts. The problem is, these chimeric pigs aren’t <em>just</em> pigs – they are also partly human.</p>
<p>If a human–pig chimera were brought to term, should we treat it like a pig, like a human, or like something else altogether?</p>
<p>Maybe this question seems too easy. But what about <a href="https://link.springer.com/protocol/10.1007/978-1-4939-9524-0_15">the idea</a> of creating monkeys with humanised brains? </p>
<h2>Chimeras are only one challenge among many</h2>
<p>Other areas of stem cell science raise similarly difficult questions. </p>
<p>In June, scientists created “<a href="https://www.theguardian.com/science/2023/jun/14/synthetic-human-embryos-created-in-groundbreaking-advance">synthetic embryos</a>” – lab-grown embryo models that closely resemble normal human embryos. Despite the similarities, they fell outside the scope of legal definitions of a human embryo in the United Kingdom (where the study took place).</p>
<p>Like human–pig chimeras, synthetic embryos straddle two distinct categories: in this case, stem cell model and human embryo. It is not obvious how they should be treated. </p>
<p>In the past decade, we have also seen the development of increasingly sophisticated <a href="https://thebiologist.rsb.org.uk/biologist-interviews/madelaine-lancaster">human cerebral organoids</a> (or “<a href="https://www.nature.com/articles/d41586-018-07402-0">lab-grown mini-brains</a>”). </p>
<p>Unlike synthetic embryos, cerebral organoids don’t mimic the development of a whole person. But they do mimic the development of the part that stores our memories, thinks our thoughts, and makes conscious experience possible. </p>
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<a href="https://images.theconversation.com/files/548452/original/file-20230915-27-pchb2a.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A microscope image shows a grid of squares covered with an irregular growth of strand-like neurons." src="https://images.theconversation.com/files/548452/original/file-20230915-27-pchb2a.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/548452/original/file-20230915-27-pchb2a.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/548452/original/file-20230915-27-pchb2a.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/548452/original/file-20230915-27-pchb2a.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/548452/original/file-20230915-27-pchb2a.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/548452/original/file-20230915-27-pchb2a.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/548452/original/file-20230915-27-pchb2a.png?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>
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<span class="caption">A network of neural cells grown on an array of electrodes to produce a ‘biological computer chip’.</span>
<span class="attribution"><a class="source" href="https://www.scienceinpublic.com.au/media-releases/dishbrain">Cortical Labs</a></span>
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<p>Most scientists think current “mini-brains” are not <a href="https://www.cell.com/trends/biotechnology/pdf/S0167-7799(23)00061-6.pdf">conscious</a>, but the field is developing rapidly. It is not far-fetched to think a cerebral organoid will one day “wake up”.</p>
<p>Complicating the picture even further are entities that combine human neurons with technology – like <a href="https://www.monash.edu/medicine/news/latest/2022-articles/brain-cells-in-a-dish-learn-to-play-pong">DishBrain</a>, a biological computer chip made by Cortical Labs in Melbourne.</p>
<p>How should we treat these <em>in vitro</em> brains? Like any other human tissue culture, or like a human person? Or perhaps <a href="https://pubmed.ncbi.nlm.nih.gov/31957593/">something in between</a>, like a research animal?</p>
<h2>A new moral framework</h2>
<p>It might be tempting to think we should settle these questions by <a href="https://www.science.org/doi/10.1126/science.aaz5221">slotting</a> <a href="https://blogs.bmj.com/medical-ethics/2021/03/18/ethics-iblastoids-and-brain-organoids-time-to-revise-antiquated-laws-and-processes/">these</a> <a href="https://www.nuffieldbioethics.org/blog/keeping-up-with-the-science-the-ethics-of-synthetic-embryos#:%7E:text=Synthetic%20embryos%20are%20not%20embryos,implanted%20and%20lead%20to%20pregnancies.">entities</a> into one category or another: human or animal, embryo or model, human person or mere human tissue.</p>
<p>This approach would be a mistake. The confusion sparked by chimeras, embryo models, and <em>in vitro</em> brains shows these underlying categories no longer make sense. </p>
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Read more:
<a href="https://theconversation.com/as-scientists-move-closer-to-making-part-human-part-animal-organisms-what-are-the-concerns-159049">As scientists move closer to making part human, part animal organisms, what are the concerns?</a>
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<p>We are creating entities that are neither one thing nor the other. We cannot solve the problem by pretending otherwise.</p>
<p>We would also need good reasons to classify an entity one way or another. </p>
<p>Should we count the proportion of human cells to determine whether a chimera counts as an animal or a human? Or should it matter where the cells are located? What matters more, brain or buttocks? And how can we work this out?</p>
<h2>Moral status</h2>
<p>Philosophers would say these are questions about “<a href="https://plato.stanford.edu/entries/grounds-moral-status/">moral status</a>”, and they have spent decades deliberating on what kinds of creatures we have moral duties to, and how strong these duties are. Their work can help us here.</p>
<p>For example, utilitarian philosophers see moral status as a matter of whether a creature has any <em>interests</em> (in which case it has moral status), and how strong those interests are (stronger interests matter more than weaker ones). </p>
<p>On this view, so long as an embryo model or brain organoid lacks consciousness, it will lack moral status. But if it develops interests, we need to take these into account. </p>
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Read more:
<a href="https://theconversation.com/networks-of-silver-nanowires-seem-to-learn-and-remember-much-like-our-brains-204115">Networks of silver nanowires seem to learn and remember, much like our brains</a>
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<p>Similarly, if a chimeric animal develops new cognitive abilities, we need to reconsider our treatment of it. If a neurological chimera comes to care about its life as much as a typical human does, then we should hesitate to kill it just as much as we would hesitate to kill a human.</p>
<p>This is just the beginning of a bigger discussion. There are other accounts of moral status, and other ways of applying them to the entities stem cell scientists are creating. </p>
<p>But thinking about moral status sets us down the right path. It fixes our minds on what is ethically significant, and can begin a conversation we badly need to have.</p><img src="https://counter.theconversation.com/content/213357/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Julian Koplin receives research funding from Ferring Pharmaceuticals.</span></em></p>Pigs with human kidneys? Brain-powered computer chips? Science is creating new kinds of living things – and our moral understanding needs to catch up fast.Julian Koplin, Lecturer in Bioethics, Monash University & Honorary fellow, Melbourne Law School, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1939842022-11-16T19:01:10Z2022-11-16T19:01:10ZSynchrony with chaos – blinking lights of a firefly swarm embody in nature what mathematics predicted<figure><img src="https://images.theconversation.com/files/495418/original/file-20221115-21-6rv7ka.jpg?ixlib=rb-1.1.0&rect=47%2C4%2C794%2C530&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Fireflies' synchronized light shows have fascinated observers for ages.</span> <span class="attribution"><span class="source">Raphael Sarfati</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p>Imagine an old-growth forest in the fading light of a summer evening. As the last of the sun’s rays disappear beneath the horizon, a tiny flash catches your eye.</p>
<p>You turn around, hold your breath; it blinks again, hovering 2 feet above the leaf litter. Across the dusky glade, a fleeting response. Then another one, and another, and within minutes flickering fireflies spread all over the quiet woods.</p>
<p>At first they seem disorganized. But soon a few coordinated pairs appear, little tandems flashing on the same tempo twice a second. Pairs coalesce into triads, quintuplets, and suddenly the entire forest is pulsating with a common, glittering beat. The swarm has reached synchrony.</p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/_pwXKKaSJ58?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Fireflies at Congaree National Park flash in unison. <em>Video by Mac Stone</em></span></figcaption>
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<p>Firefly congregations are sprawling speed-dating events. <a href="https://press.princeton.edu/books/hardcover/9780691162683/silent-sparks">Flashes convey a courtship dialogue</a> between advertising males and selective females. Shaped by the interplay of competition and cooperation among thousands of fireflies in interaction, collective light patterns emerge, twinkling analogs to the <a href="https://theconversation.com/why-do-flocks-of-birds-swoop-and-swirl-together-in-the-sky-a-biologist-explains-the-science-of-murmurations-176194">murmurations of bird flocks</a> swooping together. The mystifying phenomenon of some fireflies’ <a href="https://doi.org/10.1126/science.81.2101.339">flash synchronization has puzzled scientists for over a century</a>.</p>
<p><a href="https://www.stevenstrogatz.com/books/sync-the-emerging-science-of-spontaneous-order">Synchrony is ubiquitous throughout the universe</a>, from electron clouds to biological cycles and planetary orbits. But synchrony is a complex concept with many ramifications. It encompasses various shapes and forms, usually revealed by mathematics and later explored in nature.</p>
<p>Take the firefly swarm. Wait a little longer and among the illuminated chorus, something else appears: Some discordant flashers secede and continue off-beat. They blink at the same pace but keep a resolute delay with their conformist peers. Could this be evidence of a phenomenon predicted by mathematical equations but never seen in nature before?</p>
<h2>Synchrony, with a twist</h2>
<p>Twenty years ago, while digging deeper into the equations that form the framework of synchrony, physicists <a href="https://scholar.google.com/citations?user=K9T6BukAAAAJ&hl=en&oi=ao">Dorjsuren Battogtokh</a> and <a href="https://scholar.google.com/citations?user=UKDG5HYAAAAJ&hl=en&oi=ao">Yoshiki Kuramoto</a> noticed something peculiar. Under specific circumstances, their mathematical solutions would <a href="https://arxiv.org/abs/cond-mat/0210694">describe an ambivalent ensemble</a>, showing widespread synchrony interspersed with some erratic, free-floating constituents.</p>
<p>Their model relied on a collection of abstract clocks, called oscillators, that have a tendency to align with their neighbors. The nonuniform state was surprising, because the equations assumed all oscillators were perfectly identical and similarly connected to others.</p>
<p>Spontaneous breaking of underlying symmetry is something that typically bothers physicists. We cherish the idea that some order in the fabric of a system should translate into similar order in its large-scale dynamics. If oscillators are indistinguishable, they should either all get in sync, or all remain chaotic – not show differentiated behaviors.</p>
<p>It piqued the curiosity of many, including mathematicians <a href="https://scholar.google.com/citations?user=4VLtKDQAAAAJ&hl=en&oi=sra">Daniel Abrams</a> and <a href="https://scholar.google.com/citations?user=FxyRWlcAAAAJ&hl=en&oi=sra">Steven Strogatz</a>, who <a href="https://doi.org/10.1103/PhysRevLett.93.174102">named the phenomenon “chimera</a>.” In Greek mythology, the Chimera was a hybrid monster made of parts of incongruous animals – so a fitting name for a hodgepodge of mismatched clusters of oscillators.</p>
<p>At first, chimeras were rare in mathematical models, requiring a very specific set of parameters to materialize. Over time, learning where to scout, theorists began to uncover them in many variations of these models, dubbing them “breathing,” “twisted,” “multiheaded” and other eerie epithets. Still, it remained mysterious whether these theoretical chimeras were also possible in the physical world – or merely a mathematical myth.</p>
<p>A decade later, a few ingenious experiments set up in physics laboratories yielded the elusive chimeras. They involved finely tuned networks of interactions between sophisticated oscillators. While proving that engineering the coexistence of coherence and incoherence was a delicate, but possible, venture, they left the deeper question unanswered: Could mathematical chimeras also exist within the natural world?</p>
<p>It turned out it would take a tiny luminescent insect to shed light on them.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/495503/original/file-20221115-23-lsd1vu.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Ventral view of a small insect" src="https://images.theconversation.com/files/495503/original/file-20221115-23-lsd1vu.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/495503/original/file-20221115-23-lsd1vu.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=392&fit=crop&dpr=1 600w, https://images.theconversation.com/files/495503/original/file-20221115-23-lsd1vu.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=392&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/495503/original/file-20221115-23-lsd1vu.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=392&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/495503/original/file-20221115-23-lsd1vu.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=492&fit=crop&dpr=1 754w, https://images.theconversation.com/files/495503/original/file-20221115-23-lsd1vu.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=492&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/495503/original/file-20221115-23-lsd1vu.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=492&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">The underside of a male <em>Photuris frontalis</em> firefly, its light-producing organ in the rear.</span>
<span class="attribution"><span class="source">Raphael Sarfati</span>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
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<h2>Chimera amid the fireflies’ blinking chorus</h2>
<p>As a postdoc in the <a href="https://www.peleglab.com">Peleg Lab</a> at the University of Colorado, <a href="https://scholar.google.com/citations?user=9aaGkZQAAAAJ&hl=en">I</a> work on deciphering the <a href="https://www.lucidluminescence.org">inner workings of firefly swarms</a>. Our approach builds on the foundations of a little-known niche within modern physics: <a href="https://iopscience.iop.org/article/10.1088/1478-3975/ac4bef">animal collective behavior</a>. Simply put, the overarching objective is to reveal and characterize spontaneous, unsupervised large-scale patterns in the dynamics of groups of animals. We then investigate how these self-organized patterns <a href="https://www.quantamagazine.org/videos/what-is-emergence/">emerge</a> from individual interactions.</p>
<p>Advised by knowledgeable firefly experts, my colleagues and I drove across the country to <a href="https://www.nps.gov/cong/index.htm">Congaree National Park</a> in South Carolina to chase <em>Photuris frontalis</em>, one of few North American species <a href="https://ugapress.org/book/9780820348728/fireflies-glow-worms-and-lightning-bugs/">known to synchronize</a>. We set up our cameras in a small forest clearing among the loblolly pines. Soon after the first flickers poked through the twilight, we observed a very rhythmic, precise synchrony, apparently as clean as predicted by equations.</p>
<p>This was an enchanting experience, yet one that left me reflective. I worried that this display was too orderly to let us infer anything from it. Physicists learn about things by looking at their natural fluctuations. Here, there seemed to be little variability to investigate.</p>
<figure class="align-center ">
<img alt="Time series of asynchronous, synchronous and chimera patterns" src="https://images.theconversation.com/files/494291/original/file-20221108-15046-4wqgai.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/494291/original/file-20221108-15046-4wqgai.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=500&fit=crop&dpr=1 600w, https://images.theconversation.com/files/494291/original/file-20221108-15046-4wqgai.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=500&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/494291/original/file-20221108-15046-4wqgai.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=500&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/494291/original/file-20221108-15046-4wqgai.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=628&fit=crop&dpr=1 754w, https://images.theconversation.com/files/494291/original/file-20221108-15046-4wqgai.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=628&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/494291/original/file-20221108-15046-4wqgai.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=628&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">In an asynchronous group, individual flashes spread randomly over time. In a synchronous group, flashes cluster around specific instants. In a chimera state, a smaller group blinks to its own beat, keeping a delay from the synchronized main group. It shows up as smaller peaks between the main spikes.</span>
<span class="attribution"><span class="source">Raphael Sarfati</span></span>
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<p>Synchrony manifests itself in the data in the form of sharp spikes in the graph of the number of flashes over time. These peaks indicate that most flashes occur at the same instant. When they don’t, the trace looks irregular, like scribbles. In our plots, I first saw nothing but the flawless comblike pattern of impeccable synchrony.</p>
<p>It turned out the chimera was hiding in plain sight, but I had to roam further along the data to encounter it. There, in between the spikes of the light chorus, some shorter peaks indicated smaller factions in sync among themselves but not with the main group. <a href="https://doi.org/10.1126/sciadv.add6690">I called them “characters.”</a> Together with the synchronized chorus, these incongruous characters make up the chimera. </p>
<p>Like in the ancient Greek theater, the chorus sets the background while characters create the action. The two groups are intertwined, roaming the same stage, as we revealed from the three-dimensional reconstruction of the swarm. Despite the split in their rhythm, their spatial dynamics appear indistinguishable. Characters don’t seem to congregate or follow one another.</p>
<p>This unexpectedly intermingled self-organization raises even more questions. Do characters among the swarm consciously decide to break away, maybe to signal their emancipation? Or do they spontaneously find themselves trapped off-beat? Can mathematical insights enlighten the social dynamics at play among luminous beetles?</p>
<p>Unlike abstract oscillators in math equations, fireflies are cognitive beings. They <a href="https://doi.org/10.1080/10407413.2020.1846455">incorporate complex sensory information</a> and process it through a decision-making pipeline. They are also constantly in motion, <a href="https://doi.org/10.1126/sciadv.abg9259">forming and breaking visual bonds with their peers</a>. Streamlined mathematical models don’t yet capture these intricacies.</p>
<p>In the quiet woods, the synchronized flashes and their dissonant counterparts may have illuminated a trove of new chimeras for mathematicians and physicists to chase.</p><img src="https://counter.theconversation.com/content/193984/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Raphael Sarfati receives funding from University of Colorado Boulder. </span></em></p>Synchrony is ubiquitous throughout the universe. But physicists’ equations predicted there could also be erratic exceptions marching to their own beat. Now they’ve been spotted in firefly swarms.Raphael Sarfati, Postdoctoral Associate, University of Colorado BoulderLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1593552021-04-22T11:14:55Z2021-04-22T11:14:55ZFirst human-monkey embryos created – a small step towards a huge ethical problem<figure><img src="https://images.theconversation.com/files/396003/original/file-20210420-21-lfuv53.jpeg?ixlib=rb-1.1.0&rect=9%2C58%2C2994%2C1945&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">We believe monkeys to have lower moral status than humans – but what about human-monkey chimeras?</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/monkey-sacred-forest-ubud-bali-indonesia-1915536586">Joao Paulo Porto/Shutterstock</a></span></figcaption></figure><p>Scientists have created the world’s first <a href="https://www.telegraph.co.uk/news/2021/04/15/human-monkey-embryo-created-bid-learn-cells-communicate/">monkey embryos containing human cells</a> in an attempt to investigate how the two types of cell develop alongside each other. The embryos, which were derived from a macaque and then injected with human stem cells in the lab, were allowed to grow for 20 days before being destroyed.</p>
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<p>We have a term for this type of life form: a <a href="https://www.theguardian.com/technology/2019/aug/11/the-five-chimeras-human-monkey-hybrid-genetic">chimera</a>, named after the fire-breathing <a href="https://www.britannica.com/topic/Chimera-Greek-mythology">monster of Greek mythology</a> that was part lion, part goat and part snake. It’s hoped that part-human chimeras – essentially animal bodies with some human organs or other characteristics – might one day offer clues to help us treat human diseases, as well as providing organs to transplant to humans. But for these purposes, part-human chimeras will first have to be born, and this research takes us one step closer to that eventuality.</p>
<p>That’s ethically controversial, because these creatures could possess an ambiguous moral status: somewhere between that of humans, which we don’t tend to experiment upon, and animals, which we do. How we end up treating part-human chimeras will depend upon the moral status we assign them – a task that these latest embryonic experiments only makes more pressing.</p>
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<img alt="A bronze statue of a Chimera in a museum" src="https://images.theconversation.com/files/395973/original/file-20210420-21-zns2o9.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/395973/original/file-20210420-21-zns2o9.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/395973/original/file-20210420-21-zns2o9.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/395973/original/file-20210420-21-zns2o9.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/395973/original/file-20210420-21-zns2o9.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/395973/original/file-20210420-21-zns2o9.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/395973/original/file-20210420-21-zns2o9.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">In Greek mythology, the Chimera was said to be part lion, part goat and part snake.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/florence-italy-september-8-2020-chimera-1848914440">AlexMastro/Shutterstock</a></span>
</figcaption>
</figure>
<h2>Why make chimeras?</h2>
<p>There are several rationales for pursuing this line of research. Human-monkey chimeras could be created to study parts of the brain, for instance, so we can better understand <a href="https://www.theguardian.com/science/2019/aug/03/first-human-monkey-chimera-raises-concern-among-scientists">Alzheimer’s Disease</a>. Another goal is to grow human organs for transplantation by “deleting” the relevant organ from the animal’s genetic instructions, and replacing it with human stem cells to fill the developmental niche. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/human-animal-hybrids-are-coming-and-could-be-used-to-grow-organs-for-transplant-a-philosopher-weighs-in-121228">Human-animal hybrids are coming and could be used to grow organs for transplant – a philosopher weighs in</a>
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<p>Previously, the same researchers explored this avenue <a href="https://www.cell.com/cell/fulltext/S0092-8674(16)31752-4">in pigs</a> – seen as ideal because their organs are about the same size as ours. However, not enough human cells “took” to create a functional chimera, and the research failed. </p>
<p>Monkeys are evolutionarily closer to us, so there’s a greater chance that cells will interact effectively with each other. The stated goal of the human-monkey experiments is to understand and perfect the development of chimeras in primates before transferring the technology to pigs. </p>
<p>As we intensively farm and eat pigs, there are thought to be fewer ethical concerns with <a href="https://bioethics.georgetown.edu/2016/08/the-ethical-implications-of-harvesting-human-organs-from-pigs/">harvesting organs from pigs</a>. Hence, primate research is a stepping stone, not a goal itself.</p>
<h2>Future chimeras</h2>
<p>Whether part-pig or part-primate, living chimeras that feature human cells are certainly possible in the future. How such animals would look and function would depend, in part, on the numbers of nonhuman and human cells. Previous experiments, for instance, have produced a <a href="https://www.researchgate.net/figure/Overt-female-sheep-goat-chimera-produced-from-the-injection-of-a-caprine-ICM-Alpine_fig1_19550808">goat-sheep entity</a> that had both woolly and coarse hair.</p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/as-scientists-move-closer-to-making-part-human-part-animal-organisms-what-are-the-concerns-159049">As scientists move closer to making part human, part animal organisms, what are the concerns?</a>
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<p>This research clearly has the “<a href="https://philosophybites.com/2009/03/julian-savulescu-on-the-yuk-factor.html">yuk factor</a>”, meaning it’s likely to provoke moral revulsion. If pigs or monkeys are eventually developed with humanised features, it could cause major public opprobrium, perhaps setting back public acceptance of science significantly. </p>
<p>However, this must be balanced against the severe shortage of organs for transplantation. In the US, for example, <a href="https://www.organdonor.gov/statistics-stories/statistics.html">more that 100,000 people</a> are currently waiting for an organ.</p>
<p>We tend to get over the yuk factor when lives are at stake. The production of the AstraZeneca vaccine, for instance, uses cell lines that originated from <a href="https://www.bbc.co.uk/news/world-europe-55409693">foetal cells</a>. But behind the chimera yuk factor lies a thorny ethical problem: the issue of the moral status of monkeys or pigs that could have a brain closer to that of a human.</p>
<h2>Moral status</h2>
<p><a href="https://plato.stanford.edu/entries/grounds-moral-status/">Moral status</a> is the concept of treating life forms according to their interests and capacities. For example, humans are generally thought to have higher moral status than monkeys, who have higher moral status than pigs, who have higher moral status than worms. Moral status is linked to mental capacities such as consciousness, self-consciousness, moral capacities and rationality.</p>
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Read more:
<a href="https://theconversation.com/when-does-a-foetus-have-moral-status-94885">When does a foetus have moral status?</a>
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<p>In the future, some human-nonhuman chimeras could develop mental capacities between ordinary animals and humans. That presents a huge challenge for those of us who work to determine the moral status of living creatures, and the rights and obligations that follow that status.</p>
<p>Moral status is already one of the most contested areas of practical ethics. Recent work on “<a href="https://plato.stanford.edu/entries/moral-animal/">speciesism</a>” makes a compelling case that we have wrongly assigned animals a lower moral status. Despite this, human-nonhuman chimeras will probably be regarded as “lesser” than humans, though by how much it is difficult to determine.</p>
<p>There are two ways to tackle ethical concerns over the moral status of part-human chimeras. Scientists could genetically edit human stem cells so they do not become brain cells – but this may not be possible or even desirable, in the case of building <a href="https://www.oxfordhandbooks.com/view/10.1093/oxfordhb/9780195371963.001.0001/oxfordhb-9780195371963-e-24">models for human brain disease</a>. </p>
<p>Alternatively, scientists could allow such chimeras to be born so that we can determine their <a href="https://academic.oup.com/jlb/article/6/1/37/5489867?login=true">moral status</a> by studying them. This would raise other ethical issues, as it would require the newborn to be subjected to novel behavioural tests of cognition, communication and other mental capacities. </p>
<h2>Hybrid futures</h2>
<p>Further into the future, chimera discoveries could give humans capacities found elsewhere in the animal kingdom, like a bat’s sonar. If we accept moral status based on a creature’s capacities, such enhanced humans could one day be regarded as <a href="https://www.youtube.com/watch?v=szgMiqbR57s">superior to us</a>. </p>
<p>Seeing as we’re already struggling with issues of equality between human beings, it would seem we’re poorly prepared for the ethical challenges presented by future advances in chimera research. </p>
<p>The issue of moral status is a philosophical and ethical question. Science might help us in detecting it – with information about the extent of a non-human animal’s capacities, for instance – but it cannot tell us what it is. This new research shows it’s a concept in urgent need of attention.</p><img src="https://counter.theconversation.com/content/159355/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Julian Savulescu receives funding from Wellcome Trust and the Uehiro Foundation on Ethics and Education. He is a Partner Investigator on an Australian Research Council Linkage award (LP190100841, Oct 2020-2023) which involves industry partnership from Illumina. He does not personally receive any funds from Illumina. He presented at a Genomic Prediction-organised webinar (2021), but received no payment or other benefits from Genomic Prediction Ltd.</span></em></p><p class="fine-print"><em><span>César Palacios-González received funding on two Wellcome Trust funded research projects – as a PhD student (2012-2016) and as Research Associate (2016-2018) – on the ethics of new biotechnologies. </span></em></p>‘Chimera’ creatures with human organs could be medically useful – but can we really treat them like other animals?Julian Savulescu, Visiting Professor in Biomedical Ethics, Murdoch Children's Research Institute; Distinguished Visiting Professor in Law, University of Melbourne; Uehiro Chair in Practical Ethics, University of OxfordCésar Palacios-González, Senior Research Fellow in Practical Ethics, University of OxfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1590492021-04-19T01:51:26Z2021-04-19T01:51:26ZAs scientists move closer to making part human, part animal organisms, what are the concerns?<figure><img src="https://images.theconversation.com/files/395598/original/file-20210418-19-sfq4k5.jpg?ixlib=rb-1.1.0&rect=0%2C18%2C6123%2C3066&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>The recent announcement that scientists have made <a href="https://www.cell.com/cell/fulltext/S0092-8674(21)00305-6">human-monkey embryos</a> and cultured them in the lab for two weeks made international headlines.</p>
<p>The technology to make animals that contain cells from other species has been available for decades and used extensively in research. These organisms are called “chimeras”.</p>
<p>But this latest advance highlights the need to broaden the discussion around the possible benefits of such research and, specifically, how inter-species chimeric research should be conducted in future.</p>
<p>Human-animal chimeras blur the line about what it means to be human, and this raises serious ethical questions about how we should use them.</p>
<h2>How to make a human-animal chimera?</h2>
<p>Human-monkey chimeras were <a href="https://www.theguardian.com/science/2019/aug/03/first-human-monkey-chimera-raises-concern-among-scientists">first made</a> in 2019. Inter-species chimeras are made by mixing cells belonging to one species with those of another. </p>
<p>This usually involves conducting microsurgery to introduce “<a href="http://stemcell.childrenshospital.org/about-stem-cells/pluripotent-stem-cells-101/">pluripotent</a>” stem cells — which can develop into several different types of cells — into a host embryo from another species. </p>
<p>In the recent study, human stem cells were placed inside six-day-old monkey embryos created by fertilisation. The human-monkey embryos comprised mostly of monkey cells and some human cells. </p>
<p>These embryos were then kept in a laboratory, where researchers monitored the interactions between the human and monkey cells for up to 14 days, although most embryos didn’t survive.</p>
<h2>Why do this research?</h2>
<p>Some will find the idea of mixing human cells with any animal embryo (let alone a primate embryo) highly questionable. For the researchers who led the study, the rationale was clear. </p>
<p>They were interested in addressing the shortage of life-saving organs for human transplantation. If done successfully, a chimera could grow an organ suitable for direct transplant into a human.</p>
<p>Researchers have previously created <a href="https://www.nationalgeographic.com/science/article/human-pig-hybrid-embryo-chimera-organs-health-science">human-pig chimeras</a>, where pig embryos containing human cells were allowed to grow into a foetus. </p>
<p>However, the contribution of human cells was low and the goal to create transplantable organs remained elusive. The question of how to solve this challenge is what led to the recent experiment. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/whats-the-benefit-in-making-human-animal-hybrids-72179">What's the benefit in making human-animal hybrids?</a>
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</em>
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<p>In this recent study, researchers weren’t attempting to create human-monkey chimeras with a view to harvest organs. Rather, they created an in-vitro model (outside a living organism) to explore what happens to the transferred human cells. </p>
<p>They wanted to identify ways to enhance the survival of the human cells and ultimately improve human chimerism in pigs and other evolutionarily-distant species, with a view to developing transplantable “human” organs from animal donors. </p>
<h2>What are the issues raised?</h2>
<p>This project might conjure images of mad scientists (think <a href="https://blogs.bmj.com/medical-ethics/2020/02/11/revisiting-the-lessons-of-frankenstein/">Victor Frankenstein</a>) meddling with nature, irresponsible and without oversight. But unlike Frankenstein’s experiments, this study was not done in secret. </p>
<p>In the paper, the researchers describe in detail the steps they took to comply with international guidelines. This included extensive ethics reviews undertaken within the institutions involved and consultation with external bioethicists.</p>
<p>Of note, the study involved the use of eggs harvested from female monkeys. While the animals weren’t killed, any use of non-human primates should be approached conservatively and be consistent with international standards. </p>
<p>Research involving non-human primates is carefully scrutinised. Such projects receive <a href="https://www.nhmrc.gov.au/about-us/resources/use-non-human-primates-scientific-purposes">special consideration</a> from regulatory bodies and ethics committees around the world. </p>
<p>Nonetheless, even when conducted with ample oversight, human-animal chimera research does raise ethical questions.</p>
<p>The thorniest ones are linked not to the creation of in-vitro chimeric embryos, but rather the eventual creation of live-born chimeras, such as a human-pig chimera, if future research can overcome current limitations. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/fully-grown-pig-chimeras-are-only-a-few-years-away-we-need-to-understand-where-they-stand-now-72519">Fully-grown pig chimeras are only a few years away – we need to understand where they stand now</a>
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<h2>A future moral dilemma</h2>
<p>Humans are widely (but not universally) thought to have a higher moral status than other animals. But human-animal chimeras blur this line. They are not fully human, nor fully non-human. </p>
<p>So the big question is whether (or under what conditions) we should be allowed to use them as a source of transplantable organs, in harmful research, or for other purposes we wouldn’t use humans for. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/395556/original/file-20210417-13-1akd3pl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/395556/original/file-20210417-13-1akd3pl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/395556/original/file-20210417-13-1akd3pl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/395556/original/file-20210417-13-1akd3pl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/395556/original/file-20210417-13-1akd3pl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/395556/original/file-20210417-13-1akd3pl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/395556/original/file-20210417-13-1akd3pl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/395556/original/file-20210417-13-1akd3pl.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>
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<span class="caption">Of all non-human animal species, chimpanzees are genetically the closest to humans.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
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</figure>
<p>These concerns will be most acute for chimeras with human-like brains, wherein human cells are incorporated into an animal’s brain during development. </p>
<p>Humans pride themselves on their autonomy, rationality and sophisticated self-awareness. If a human-pig chimera developed this capacity, it may have a moral claim to be treated more like a human than a pig. </p>
<p>The study raises a second ethical concern that is more immediately relevant. Using recent advances in monkey-embryo culture, the researchers cultured some embryos until 19 days post-fertilisation. </p>
<p>Many jurisdictions explicitly limit human embryo research to the first 14 days of development, when what will become the central nervous system begins to develop. </p>
<p>Should the 14-day limit also apply to human-animal chimeric embryos? </p>
<p>Perhaps it should depend on the proportion of human cells in developing chimeric embryo. Although, this leaves us with the question of how many human cells is too many. </p>
<p>Or perhaps, as <a href="https://www.eurekalert.org/pub_releases/2021-02/b-e1h012821.php#">some have argued</a>, the 14-day rule ought to be revised. </p>
<h2>How should we manage these concerns?</h2>
<p>Like many other aspects of stem cell research, we can find a starting point in guidelines from the <a href="https://www.isscr.org/">International Society for Stem Cell Research</a>. </p>
<p>These standards, soon to be updated, explicitly recommend specialised review for human-animal chimera research. This includes monitoring chimeric animals for unexpected behaviours that indicate suffering, which could then be addressed under existing animal ethics principles. </p>
<p>Experts <a href="https://jme.bmj.com/content/45/7/440">say</a> it might be worth monitoring chimeric animals for evidence they may be autonomous, rational, or self-aware — and modifying their treatment accordingly. </p>
<p>Given the ethical complexity and sensitivity of human-animal chimera research, it’s crucial it receives careful oversight. As the field develops we must continuously review where the boundaries of the research lie. </p>
<p>And these conversations must not only explore animal welfare, but also how potential patients and the broader community view access to organs derived from donor animals.</p><img src="https://counter.theconversation.com/content/159049/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Megan Munsie receives funding from the Australian Research Council and the Medical Research Future Fund. She is a non-executive director with the National Stem Cell Foundation of Australia, Vice-President of the Australasian Society for Stem Cell Research, Chair of the Ethics Committee of the International Society for Stem Cell Research and a member of the taskforce currently updating the ISSCR Guidelines.</span></em></p><p class="fine-print"><em><span>Julian Koplin does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Researchers made human-monkey chimeras, by adding human stem cells to monkey embryos. Some embryos were cultured for 19 days after fertilisation.Megan Munsie, Deputy Director - Centre for Stem Cell Systems and Head of Engagements, Ethics & Policy Program, Stem Cells Australia, The University of MelbourneJulian Koplin, Resarch Fellow in Biomedical Ethics, Melbourne Law School and Murdoch Children's Research Institute, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1214732019-09-03T12:53:14Z2019-09-03T12:53:14ZGenetic engineering and human-animal hybrids: how China is leading a global split in controversial research<figure><img src="https://images.theconversation.com/files/290754/original/file-20190903-175678-1508peu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/medical-doctors-looking-futuristic-tablet-device-1085160959?src=-2-60">metamorworks/Shutterstock</a></span></figcaption></figure><p>If you want to conduct groundbreaking but contentious biological research, go to China. Last year, Chinese scientist He Jiankui announced he had created the world’s <a href="https://theconversation.com/how-a-scientist-says-he-made-a-gene-edited-baby-and-what-health-worries-may-ensue-107764">first gene-edited human babies</a>, shocking the world at a time when such practice is illegal in most leading scientific nations. More recently, US-based researcher Juan Carlos Izpisua Belmonte revealed he had produced the world’s <a href="https://elpais.com/elpais/2019/07/31/inenglish/1564561365_256842.html">first human-monkey hybrid</a> embryo in China to avoid legal issues in his adopted country.</p>
<p>Yet if China is fast becoming the world capital of controversial science, it is not alone in producing it. More babies produced using the “CRISPR” gene-editing technology <a href="https://www.nature.com/articles/d41586-019-01770-x">are now planned</a> by a scientist in Russia, where another researcher is also hoping to conduct the world’s <a href="https://theconversation.com/the-problem-with-human-head-transplants-53522">first human head transplant</a>. And Japan has <a href="https://theconversation.com/human-animal-hybrids-are-coming-and-could-be-used-to-grow-organs-for-transplant-a-philosopher-weighs-in-121228">recently lifted</a> its own ban on human-animal hybrids.</p>
<p>The world is rapidly moving towards a two-tier system of cutting-edge medical research, broadly divided between countries with minimal regulation and those that refuse to allow anything but the earliest stages of this work. The consequences of this split are likely to be significant, even potentially affecting your own access to healthcare.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/290743/original/file-20190903-175700-15ol419.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/290743/original/file-20190903-175700-15ol419.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/290743/original/file-20190903-175700-15ol419.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/290743/original/file-20190903-175700-15ol419.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/290743/original/file-20190903-175700-15ol419.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/290743/original/file-20190903-175700-15ol419.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/290743/original/file-20190903-175700-15ol419.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">
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<span class="caption">He Jiankui.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:He_Jiankui.jpg">The He Lab/Wikipedia</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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</figure>
<p>The births of the CRISPR babies in China <a href="https://www.nature.com/articles/d41586-019-00673-1">led to uproar</a> among the scientific community, which <a href="https://theconversation.com/worlds-first-gene-edited-babies-premature-dangerous-and-irresponsible-107642">criticised He Jiankui</a>, and inspired <a href="https://theconversation.com/experts-call-for-halt-to-crispr-editing-that-allows-gene-changes-to-pass-on-to-children-113463">calls for a halt</a> in any CRISPR research on human embryos. <a href="https://rbej.biomedcentral.com/articles/10.1186/1477-7827-12-108">In around 30 countries</a>, gene editing of human embryos is already banned outright or at least tightly controlled. For example, in the UK only a handful of research groups have been <a href="https://www.crick.ac.uk/research/labs/kathy-niakan/human-embryo-genome-editing-licence">granted a licence</a> to conduct experiments, and certainly not with any aim of bringing an embryo to term.</p>
<p>But in most countries, things are <a href="https://socialandlegalstudies.wordpress.com/2019/07/12/whats-law-got-to-do-with-human-germline-editing/">less clear</a>. The Chinese establishment was <a href="https://www.theguardian.com/science/2018/nov/29/work-on-gene-edited-babies-blatant-violation-of-the-law-says-china">quick to condemn</a> He’s work and declare it illegal. And some commentators have <a href="https://www.theatlantic.com/science/archive/2018/11/china-crispr-babies/576784/">made the point</a> that, despite outside perceptions, Chinese science is far from unregulated. Yet the fact remains that He was able to conduct the work unimpeded, with evidence suggesting he may have even received <a href="https://www.theverge.com/2019/2/26/18241382/crispr-babies-chinese-government-he-jiankui-bioethics-science-health">state funding</a>.</p>
<p>With a technology moving as <a href="https://theconversation.com/uk/topics/crispr-15704">quickly as CRISPR</a>, many nations will not have had the time nor expertise to develop a comprehensive stance. As a result, it seems likely that we won’t be able to avoid a two-tier system for this kind of research. Nations with developed regulation for biotechnology will be able to adapt more quickly and easily to the latest advances and put restrictions in place. Other states will scramble to keep up, leaving scientists to proceed without having to consider the ethical or social implications of their work. And that’s assuming all governments want to restrict this kind of research, which they may not.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/290685/original/file-20190903-175682-jomjl9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/290685/original/file-20190903-175682-jomjl9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/290685/original/file-20190903-175682-jomjl9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/290685/original/file-20190903-175682-jomjl9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/290685/original/file-20190903-175682-jomjl9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/290685/original/file-20190903-175682-jomjl9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/290685/original/file-20190903-175682-jomjl9.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">
<figcaption>
<span class="caption">Not all countries may want to restrict gene editing.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/innovative-technologies-science-medicine-mixed-media-493402678">Sergey Nevens/Shutterstock</a></span>
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<p>We have seen what happens when there is this kind of international disconnect with other biotechnologies. “Medical tourism” has become a <a href="https://doi.org/10.1016/j.amjmed.2018.06.022">boom sector</a> within the healthcare industry. People travel from all over the world to private clinics that provide – or <a href="https://www.nytimes.com/2016/06/23/health/a-cautionary-tale-of-stem-cell-tourism.html">claim to provide</a> – stem cell therapies unavailable in their home countries. There have been high-profile cases of people travelling from the <a href="https://ipscell.com/2016/09/mitochondrial-replacement-techniques-mexican-case/">US to Mexico</a> in order to skirt national laws and access mitochondrial replacement therapy. </p>
<p>So it’s safe to assume that those with the means to do so might try to access gene editing abroad when it’s not available in their own countries, perhaps to avoid passing on a known heritable condition they carry. And with home DNA-testing kits becoming widespread (<a href="https://www.scientificamerican.com/article/how-accurate-are-online-dna-tests/">although not necessarily accurate</a>), the number of people wanting to edit their genome before having children is likely to increase.</p>
<p>A lack of or loose medical regulations also tends to produce predatory clinics that <a href="https://www.imtj.com/blog/stem-cell-therapies-show-medical-tourisms-darker-side/">charge huge amounts</a> for what sounds like wonder cures but might be, at best, a sugar pill or, at worst, <a href="https://stemcellsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/sctm.17-0282">something actively harmful</a>. And, perhaps worst of all, regulatory problems might contribute to destroying the reputation of promising developing medical technologies. The more nasty incidents that are attributed to an unregulated therapy, the less and less willing people will be to support legitimate medical trials.</p>
<p>This kind of two-tier system of medical regulation could also lead techniques such as gene-editing to become much more culturally accepted in some countries than others. Our society continues to struggle with xenophobia and racism, so we may also find prejudices and legal dilemmas developing for genetically engineered humans (never mind human-animal hybrids).</p>
<p>Would people born using technologies such as CRISPR be allowed to visit or emigrate to countries where their very creation was illegal? Would it be illegal for them to have their own children and spread their genetically altered genome? This kind of conflict between international human rights legislation and domestic policy is yet to be tested but could have grave consequences.</p>
<h2>Worsening health inequality</h2>
<p>On the other side of the divide, if countries with strong regulations move too slowly to allow treatments that may be lifesaving or disability preventing, it could worsen health inequality. We already have serious global problems with <a href="http://www.jpe.ox.ac.uk/papers/biotechnology-justice-and-health/">distributive justice</a>, the ways in which services or technologies are only accessible to the privileged. If a particular illness could be prevented through CRISPR, is it right that someone should have to risk their child developing the disease just because they cannot afford to travel to a country where the technique is legal?</p>
<p>Unfortunately, the obvious solution – internationally agreed standards and regulations – may be a pipedream. We have consistently failed to find <a href="https://www.oxfordhandbooks.com/view/10.1093/oxfordhb/9780199680832.001.0001/oxfordhb-9780199680832-e-58">global consensus</a> on gene editing issues, just as with embryo research. Even if it is possible to reach common ground, developing and implementing mutually acceptable terms that are flexible enough to handle the inevitable further technological progress, will take many years. For now, proposals for <a href="https://www.nature.com/articles/d41586-018-03270-w">concerted effort to keep track</a> of gene editing research may be the best we can do.</p>
<p>It’s difficult to predict what could happen in the meantime. But it seems likely that more and more gene editing and other controversial practices will take place in a variety of regulated and unregulated circumstances. Sadly, it may be the case that little progress is made until the types of problems outlined above become all too real.</p><img src="https://counter.theconversation.com/content/121473/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>David Lawrence does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>A growing international divide over cutting-edge medical research could worsen predatory practices, medical tourism and health inequality.David Lawrence, Postdoctoral Fellow, Newcastle Law School, Newcastle UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1212282019-08-02T10:27:27Z2019-08-02T10:27:27ZHuman-animal hybrids are coming and could be used to grow organs for transplant – a philosopher weighs in<figure><img src="https://images.theconversation.com/files/286640/original/file-20190801-169688-1mprhc2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Pigs growing human pancreases, coming to a farm near you soon?</span> <span class="attribution"><span class="source">shutterstock</span></span></figcaption></figure><p>Around the world thousands of people are on organ donor waiting lists. While some of those people will receive the <a href="http://www.transplant-observatory.org/">organ transplants</a> they need in time, the sad reality is that many will die waiting. But controversial new research may provide a way to address this crisis.</p>
<p>Japan has recently overturned its ban on the creation of human-animal hybrids, or “chimeras”, and <a href="https://www.nature.com/articles/d41586-019-02275-3">approved a request by researchers from the University of Tokyo</a> to create a <a href="https://theconversation.com/whats-the-benefit-in-making-human-animal-hybrids-72179">human-mouse hybrid</a>.</p>
<p>Scientists will attempt to grow a human pancreas inside a mouse, using a certain kind of stem cell known as “induced pluripotent stem cells”. These are cells that can grow into almost any kind of cell. The stem cells will be injected into a mouse embryo, which has been genetically modified to be incapable of producing a pancreas using its own cells. This hybrid embryo is then implanted in a mouse surrogate and allowed to grow. The goal is to eventually grow a human pancreas in a larger animal – such as a pig – which can be transplanted into a human.</p>
<p><a href="https://theconversation.com/human-pig-chimeras-may-provide-vital-transplant-organs-but-they-raise-ethical-dilemmas-60648">Human-animal hybrids</a> have been created in both the US and UK, but <a href="https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/491496/Animals_Containing_Human_Material_Final_Guidance.pdf">regulations</a> require the embryo to be destroyed usually by 14 days. The new Japanese regulations allow for the embryo to be implanted in a surrogate uterus, and eventually, to be born as a mouse with a “human” pancreas. The mice will then be monitored for up to two years, to see where the human cells travel and how the mice develop.</p>
<h2>Ethical issues</h2>
<p>The idea of <a href="https://theconversation.com/how-long-before-we-can-transplant-an-animals-heart-in-a-human-57701">human-animal hybrids</a> can raise a lot of questions and it’s easy to feel they are “unnatural” because they violate the boundaries between species. But the boundary between species is often fluid, and we don’t seem to have the same reaction to animal hybrids like mules, or the many kinds of plant hybrids humans have produced.</p>
<p><a href="https://www.tandfonline.com/doi/abs/10.1162/15265160360706417">Philosophers</a> believe that negative reactions to human-animal hybrids might be based on our need to have a <a href="https://theconversation.com/wary-of-human-animal-hybrids-its-probably-just-your-own-moral-superiority-72720">clear boundary</a> between things that are “human” and things that are not. This distinction grounds many of our social practices involving animals, and so threatening this boundary could create moral confusion. </p>
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Read more:
<a href="https://theconversation.com/how-much-should-you-be-told-about-your-organ-donor-35118">How much should you be told about your organ donor?</a>
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<p>Some might feel that human-animal hybrids are a threat to human dignity. But it’s difficult to specify what this claim really amounts to. A stronger objection is the idea that a human-animal hybrid may acquire human characteristics, and as a result, be entitled to human level moral consideration. </p>
<p>If, for example, the injected human stem cells travel to the mouse’s brain, it could develop enhanced cognitive capacities compared to a normal mouse. And on that basis, it may be entitled to a <a href="https://fewd.univie.ac.at/fileadmin/user_upload/inst_ethik_wiss_dialog/Singer__P._2009._Speciesism_and_Moral_Status_44245648.pdf">much higher moral status</a> than a mouse would normally be granted – and possibly make it unethical for use in scientific experimentation.</p>
<h2>Moral status</h2>
<p>Moral status tells us whose interests count, from a moral point of view. Most people would say human beings have full moral status, as do babies, fetuses and the severely disabled, which means we must consider their interests. More controversially, some people also believe that non-human animals – such as <a href="https://www.nonhumanrights.org/blog/cecilia-chimpanzee-legal-person/">chimpanzees</a> or <a href="https://harvardmagazine.com/2007/05/the-moral-status-of-the.html">human embryos</a> – possess a degree of moral status approaching that of human beings. </p>
<p>But pinning down what characteristics confer moral status can be tricky. <a href="https://plato.stanford.edu/entries/grounds-moral-status/#SpecRela">Various criteria have been suggested</a>, including the ability to reason, have self-awareness, the ability to form relationships with others, the capacity for suffering, or simply being a part of the human species. But each of these criteria ends up including some groups who don’t have moral status, or excluding some who do.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/286644/original/file-20190801-169692-1er7dbo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/286644/original/file-20190801-169692-1er7dbo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=391&fit=crop&dpr=1 600w, https://images.theconversation.com/files/286644/original/file-20190801-169692-1er7dbo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=391&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/286644/original/file-20190801-169692-1er7dbo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=391&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/286644/original/file-20190801-169692-1er7dbo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=491&fit=crop&dpr=1 754w, https://images.theconversation.com/files/286644/original/file-20190801-169692-1er7dbo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=491&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/286644/original/file-20190801-169692-1er7dbo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=491&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A human-animal chimera contains a mixture of human cells and animals cells.</span>
<span class="attribution"><span class="source">Pexels</span></span>
</figcaption>
</figure>
<p>The idea that non-human animals might have sufficient moral status for it to be morally wrong to kill them for food, or use for medical research, has gained significant traction in the philosophical community. Similarly, veganism has grown massively worldwide. There’s been a <a href="https://www.reportbuyer.com/product/4959853/top-trends-in-prepared-foods-2017-exploring-trends-in-meat-fish-and-seafood-pasta-noodles-and-rice-prepared-meals-savory-deli-food-soup-and-meat-substitutes.html">600% increase in people identifying as vegan</a> in the US in just the last three years. While in the UK the number of vegans has risen from <a href="https://www.vegansociety.com/news/media/statistics">150,000 in 2014 to 600,000 in 2018</a>, which suggests people are increasingly willing to take the <a href="https://theconversation.com/vegan-diet-how-your-body-changes-from-day-one-100413">interests of animals</a> seriously.</p>
<p>From a philosophical perspective using non-human animals for food or medical research is unethical because it significantly harms the animal, while providing only a small or insignificant benefit to us. But even those who believe that non-human animals have moral status would likely support sacrificing the life of a non-human animal to save the life of a human – as would be the case in human-animal organ donation. This is because a human can value its life in complex ways that a non-human animal cannot. </p>
<p>But if human-animal hybrids become more like us than non-human animals, it could then be argued that it’s unethical to produce a hybrid simply for the purposes of extracting its organs. That is, harvesting the organs of a non-consenting human-animal hybrid could be morally equivalent to <a href="https://theconversation.com/organ-trafficking-a-protected-crime-16178">harvesting the organs</a> of a non-consenting human. </p>
<p>Of course, for this argument to work, there would need to be strong reasons for thinking not only that a human-animal hybrid has moral status, but that its life has equal moral value to that of a human. And even if a mouse-human hybrid did have a “human-like” brain, it is exceedingly unlikely that it would be human enough to merit equal moral consideration. </p>
<p>So given that this process has the potential to successfully resolve the perpetual lack of organs for transplant, it’s reasonable to think that the use of human-animal hybrids is the right thing to do to <a href="https://theconversation.com/pig-implants-could-deliver-insulin-to-people-with-diabetes-19178">help save human lives</a> – even if it does require some level of animal suffering.</p><img src="https://counter.theconversation.com/content/121228/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mackenzie Graham does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The idea of human-animal hybrids can raise a lot of questions and it’s easy to feel they are “unnatural” because they violate the boundaries between species.Mackenzie Graham, Research Fellow of Philosophy, University of OxfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/727202017-02-19T19:08:39Z2017-02-19T19:08:39ZWary of human-animal hybrids? It’s probably just your own moral superiority<figure><img src="https://images.theconversation.com/files/157085/original/image-20170216-27409-1715lng.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The idea of human-animal hybrids often leads to people picturing something like an ancient Greek monster, such as the Chimera.</span> <span class="attribution"><span class="source">Wikimedia</span></span></figcaption></figure><p>In Greek mythology, the <a href="https://en.wikipedia.org/wiki/Chimera_(mythology)">Chimera</a> is a monstrous fire-breathing creature, typically described as having the head of a lion, with a snake as a tail and the head of a goat emerging from its back. </p>
<p>Just as it terrorised the minds of the Greeks, this vision is also the cause of much consternation regarding the successful creation of the first <a href="http://www.cell.com/cell/fulltext/S0092-8674(16)31752-4">human-pig hybrid embryos</a> at the Salk Institute in California. In fact, such human-animal hybrids are often referred to as “chimeras”.</p>
<p>While this scientific advance offers the prospect of growing human organs inside animals for use in transplants, it can also leave some people with a queasy feeling. It was precisely this queasiness that led to the <a href="https://www.theguardian.com/science/2017/jan/26/first-human-pig-chimera-created-in-milestone-study">moratorium on funding</a> for this program of research. </p>
<p>People, it seems, just can’t stomach the idea of growing human kidneys in pigs!</p>
<p>Given the <a href="https://theconversation.com/whats-the-benefit-in-making-human-animal-hybrids-72179">potential advances</a> that this research offers, our objections should probably be based on more than a mild case of nausea. Yet there are a few enduring aspects to the way we perceive human-animal hybrids that makes it difficult to think about them clearly.</p>
<h2>It’s just not natural!</h2>
<p>Many of us are like six-year-olds who turn their nose up at the idea of mixing their broccoli with their mashed potato. We prefer to keep things pure. <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/j.1467-839X.2010.01315.x">A 2010 study found</a> that whether it is cross-bred animals or racially mixed children, people who see the world as defined by underlying essences tend to reject this “impurity”. </p>
<p>What is an “underlying essence”? It’s the idea that things have certain necessary properties that are essential to them being what they are. So there is a kind of “pigness” that is exclusive to pigs, and a “humanness” that is exclusive to us.</p>
<p>But in biology, at least, there is no actual essence to anything in this sense. We’re all made of different combinations of the same kinds of stuff, like proteins and amino acids. Even much of the blueprint – our genes and DNA – are shared across species, such that humans and mice share around <a href="http://education.seattlepi.com/animals-share-human-dna-sequences-6693.html">90% of their DNA</a>, and we even share around <a href="http://genome.wustl.edu/genomes/detail/caenorhabditis-elegans/">35% of our genes</a> with the simple roundworm. </p>
<p>But this does not mean that we don’t often rely on this way of thinking to understand what makes a tiger natural in a way that a chair is not. It is also this intuition that makes us squirm at the thought of a tiger-goat but intrigued by the idea of a chair-table.</p>
<p>Mixing human and animal biology is perceived as being unnatural and bit on the nose (much like a laksa risotto I once ordered), creating an irrational fear that human-pigs might escape the lab and take over the world (much like I fear the meteoric rise of Italian-Malay cuisine).</p>
<p>While the possibility of human-pig chimera wandering the planet is far from reality, just like the Greeks, our fear of hybrids fosters the sense that such creatures would be monstrous.</p>
<h2>But what about mules?</h2>
<p>While hybrids in general can sometimes create a disagreeable mixture of fear and disgust, this is not always the case. Take for instance the boysenberry (a cross between the raspberry, blackberry, dewberry and loganberry) or the clementine (a cross between a mandarin and an orange). We have little trouble consuming such hybrids for our lunch.</p>
<p>Our apparent comfort with some hybrids does not stop at plants. Mules have never been a source of alarm, yet they are the offspring of a male donkey and a female horse. And what about the <a href="http://www.boredpanda.com/strange-hybrid-animals-that-are-hard-to-believe-actually-exist/">Liger, Tigon, Zonkey, Geep, or Beefalo</a>? </p>
<p>Still, while hybrids in general can create a sense of foreboding, not all hybrids do, and it may be that mixing biology is most psychologically problematic when it comes to our own human DNA – and perhaps especially when it comes to mixing it with that of other animals. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/157086/original/image-20170216-27396-112r8x3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/157086/original/image-20170216-27396-112r8x3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/157086/original/image-20170216-27396-112r8x3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=454&fit=crop&dpr=1 600w, https://images.theconversation.com/files/157086/original/image-20170216-27396-112r8x3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=454&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/157086/original/image-20170216-27396-112r8x3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=454&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/157086/original/image-20170216-27396-112r8x3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=571&fit=crop&dpr=1 754w, https://images.theconversation.com/files/157086/original/image-20170216-27396-112r8x3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=571&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/157086/original/image-20170216-27396-112r8x3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=571&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A common theme for depictions of monsters is human-animal hybrids.</span>
<span class="attribution"><span class="source">Wikimedia</span></span>
</figcaption>
</figure>
<h2>We are not animals</h2>
<p>One reason that human-pig hybrids are a source of anxiety is that they can conjure up a fear of our own death. The possibility that a pig could grow your next pancreas is a cogent reminder that humans are also animals, and this very biological reminder can create <a href="http://psycnet.apa.org/journals/xge/130/3/427/">existential angst</a>. </p>
<p>The notion that humans have souls, but animals do not, was (and still is for some) a popular belief. It gives us a sense of being superior, above or outside the biological order. Harvesting human hearts from goats can shatter this protective belief, leaving us feeling disgusted and dismayed.</p>
<p>Human-animal hybrids turn one’s mind to the inevitable fact that we will all be pushing up the daisies one day. By keeping thoughts of our animal nature at bay, we conveniently forget that we are nothing more than mortal biological organisms waiting to fertilise the fields.</p>
<h2>But bacon tastes good!</h2>
<p>Another reason that growing a spare liver in the pig on your uncle’s farm while subjecting your own to a bad case of cirrhosis may create unease is that doing so confuses the tastebuds. We eat pigs, not humans. Would you still enjoy bacon if it came from the pig who had nursed your liver for the past six months?</p>
<p>More powerfully, the prospect of pig-humans also confuses the moral compass. Biologically merging pigs with humans reminds us of our shared similarities, something that we mostly <a href="http://journals.sagepub.com/doi/abs/10.1177/0146167211424291">try to forget</a> when savouring the smell of frying bacon.</p>
<p>We tend to maintain clear boundaries between <a href="http://www.sciencedirect.com/science/article/pii/S0195666311001413">those animals we eat and those we do not</a>, as this helps to resolve the <a href="http://journals.sagepub.com/doi/abs/10.1177/1088868316647562">sense of discomfort</a> that we might otherwise feel about using animals for food. It was this very confusion of boundaries that led to outrage over the prospect of horse meat in burgers during the <a href="http://theconversation.com/neigh-sayers-why-we-wont-agree-to-eat-a-dead-horse-12212">2013 horse meat scandal</a>; horses are perceived as pets or companions, not food.</p>
<p>If confusing pets with animals we eat creates discontent, then confusing those same meat-animals with our own kind is sure to create moral and gustatory hesitation. </p>
<p>Beyond baffling our palate, it also confounds our understanding of whether it is an animal from whom we are harvesting our next-generation organs, or some kind of sub-human entity. Indeed, harvesting organs from humans conjures visions of a <a href="https://en.wikipedia.org/wiki/The_Island_(2005_film)">dystopian future</a>.</p>
<p>In the end, while mythical hybrid beasts may have caused alarm for the Greeks, it would seem that our own objection to growing our next heart in the breast of a pig has more to do with existential angst and a disruption of the moral order. </p>
<p>Whether or not we should use animals for these purposes, or for the satisfaction of human needs more broadly, is a topic for another time. Yet it is safe to say that our personal fear of this scientific advance – the queasiness we feel in the gut – may be mostly to do with how it destabilises our perceived human uniqueness and undermines our own moral superiority than anything to do with broader concerns over hybrids themselves. </p>
<p><em>Editor’s note: we have modified the wording to clarify that examples of cross-bred animals and racially mixed children are from a 2010 study on essentialist attitudes.</em></p><img src="https://counter.theconversation.com/content/72720/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Brock Bastian does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The concept of creating human-animal hybrids can be eerie, but that’s only because of the way our minds tend to categorise things.Brock Bastian, Professor, Melbourne School of Psychological Sciences, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/725192017-02-13T11:32:44Z2017-02-13T11:32:44ZFully-grown pig chimeras are only a few years away – we need to understand where they stand now<figure><img src="https://images.theconversation.com/files/156070/original/image-20170208-17349-1j16jen.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Scientists have made a massive breakthrough.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/cute-piglet-air-hands-female-veterinarian-387527650">Shutterstock</a></span></figcaption></figure><p>If you needed an organ transplant, would you mind if it had been grown in an animal from human stem cells? Or would you do it but deep down find it frighteningly unnatural? This may all sound like science fiction, but scientists recently managed to implant human stem cells <a href="http://www.cell.com/cell/fulltext/S0092-8674(16)31752-4">into a pig embryo</a> – pushing us a step closer to <a href="http://www.americantransplantfoundation.org/about-transplant/facts-and-myths/">such a future</a>. There are also other important applications from such research, such as the study of developmental processes and diseases of many kinds.</p>
<p>We are, at minimum, several steps and several years away from being able to create fully grown <a href="http://news.nationalgeographic.com/2017/01/human-pig-hybrid-embryo-chimera-organs-health-science/">human-animal chimeras</a>. But worries over the ethics of chimera research have been with us since the beginning of the 21st century. Ethicists have begun to map the space of difficult moral questions surrounding this issue. </p>
<p>In a useful recent survey, Robert Streiffer identified <a href="https://plato.stanford.edu/entries/chimeras/">several distinct concerns</a> and discussed whether they were worthy of attention. Many readers will share these concerns, although they leave me fairly cold. One is that creating chimeras is wrong because it violates boundaries between species – it is in some morally problematic way unnatural. Another is that the creation of chimeras will threaten social practices that depend on a strong human-animal distinction, such as the farming of animals for food, and so create moral confusion. Many people also believe that chimeric research will threaten human dignity.</p>
<p>One area of concern that I do find salient and important, however, has to do with the moral status of chimeric beings. As Streiffer also noted, if a chimeric animal’s moral status is enhanced then society must be prepared to deal with it. As an extreme example, consider a chimera with human-like cognitive abilities but without the physical ability to speak. Such a chimera could conceivably be raised in a society that hasn’t thought about how to address this and places no weight on its enhanced cognition. </p>
<p>If enhanced cognitive abilities are a basis for enhanced moral status, this might be ethically problematic. But confronting this problem requires a sophisticated understanding of what “moral status” means and of how chimeric research might enhance this in an animal.</p>
<h2>Upping status</h2>
<p>And it’s not clear that we have a sufficient understanding of this. This is because most accounts of moral status are designed to consider only two things. One is that healthy human beings fully qualify for it – their interests matter morally, and there are strong moral reasons against harming or killing them. The other is that some privileged population – for example babies, foetuses, those with severe cognitive disabilities or non-human animals – is close enough along some relevant dimension to qualify for similar protections. </p>
<p>These things in combination can lead to a lot of confusion. Although each of these marginalised groups present unique concerns, in each case we’re supposed to draw a theoretical connection between them and that of healthy human adults. The idea is usually that these groups demonstrate some capability or property that we find morally significant in our own case, and that in virtue of this the marginalised group deserves moral consideration.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/156357/original/image-20170210-23354-1szrru4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/156357/original/image-20170210-23354-1szrru4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=336&fit=crop&dpr=1 600w, https://images.theconversation.com/files/156357/original/image-20170210-23354-1szrru4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=336&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/156357/original/image-20170210-23354-1szrru4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=336&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/156357/original/image-20170210-23354-1szrru4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=423&fit=crop&dpr=1 754w, https://images.theconversation.com/files/156357/original/image-20170210-23354-1szrru4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=423&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/156357/original/image-20170210-23354-1szrru4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=423&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Special status for foetuses? Pro Life Rally For Life In Dublin.</span>
<span class="attribution"><span class="source">William Murphy</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>But healthy human adults are complicated creatures, with a range of morally relevant capacities and characteristics. Healthy human adults are sentient, they enjoy sophisticated moral agency, they are self-conscious and they enjoy rich inner lives full of a range of complicated emotions. They also participate in complicated forms of social interaction, friendship and cooperation. If we wish to extend moral status to some population, for example to foetuses, we will probably pick a subset of these capacities to be able to include them. Or try some alternative way to demonstrate that the population meets similar criteria as healthy human adults. </p>
<p>But what we’re left with is a <a href="https://philpapers.org/rec/DEGHCH">mishmash of accounts of moral status</a>, and of the things that might enhance or diminish it. Moral philosophers have suggested that these range from self-consciousness and sophisticated psychological capacities, to simply the capacity to suffer or to participate in relationships that could fundamentally transform behaviour. Other suggestions include having the genetic basis for moral agency (would human genes in a human/pig chimera count?) or the fact that one might have been or might become a person.</p>
<p>It is unclear how well any of these proposals would relate to the case of chimeras. Our understanding of what kinds of chimeras we may be able to create is still in its infancy. It is unclear whether chimeras will share features with the problem cases that drive much work in ethics on moral status. For example, will growing a human heart or some human neurons in a pig mean that it might have been a person, and is this morally significant? </p>
<p>The current approach to determining moral status is problematic. It is not a great theoretical procedure to develop a new patch each time a theoretical dyke springs a leak. </p>
<p>It may be that what we need to do is to go back to the drawing board with respect to moral status, and to think hard about the kinds of things that underpin our practices and our moral judgements regarding human adults. For difficult cases like the human-animal chimera, ethical thought on moral status may not yet be fit for purpose.</p>
<hr>
<p><em>In conjunction with Oxford University’s <a href="http://blog.practicalethics.ox.ac.uk/">Practical Ethics</a> blog</em></p><img src="https://counter.theconversation.com/content/72519/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Joshua Shepherd receives funding from the Wellcome Trust, award 104347. </span></em></p>What rights should a chimera with human-like cognitive abilities but without the ability to speak have?Joshua Shepherd, Wellcome Trust Research Fellow in Philosophy, University of OxfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/721792017-02-01T23:13:37Z2017-02-01T23:13:37ZWhat’s the benefit in making human-animal hybrids?<figure><img src="https://images.theconversation.com/files/155146/original/image-20170201-12681-90tftv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The red shows rat cells in the developing heart of a mouse embryo.</span> <span class="attribution"><span class="source">Salk Institute</span></span></figcaption></figure><p>A team of scientists from the Salk Institute in the United States created a stir last week with the <a href="http://www.cell.com/cell/fulltext/S0092-8674(16)31752-4">announcement</a> that they had created hybrid human-pig foetuses.</p>
<p>The story was widely reported, although some outlets took a more <a href="https://www.thesun.co.uk/news/2713619/scientists-make-pig-human-babies-by-splicing-stem-cells-in-amazing-new-trial/">hyperbolic</a> or <a href="http://www.lifenews.com/2017/01/27/scientists-create-human-pig-hybrids-for-organ-transplants-that-could-develop-into-monsters/">alarmed</a> tone than <a href="http://www.nature.com/news/hybrid-zoo-introducing-pig-human-embryos-and-a-rat-mouse-1.21378">others</a>.</p>
<p>One might wonder why scientists are even creating human-animal hybrids – often referred to as “<a href="https://www.britannica.com/topic/chimera-genetics">chimeras</a>” after the <a href="https://en.wikipedia.org/wiki/Chimera_(mythology)">Greek mythological creature</a> with features of lion, goat and snake.</p>
<p>The intention is not to create new and bizarre creatures. Chimeras are incredibly useful for understanding how animals grow and develop. They might one day be used to grow life-saving organs that can be transplanted into humans.</p>
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<a href="https://images.theconversation.com/files/155148/original/image-20170201-12685-1l79wjf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/155148/original/image-20170201-12685-1l79wjf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/155148/original/image-20170201-12685-1l79wjf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=353&fit=crop&dpr=1 600w, https://images.theconversation.com/files/155148/original/image-20170201-12685-1l79wjf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=353&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/155148/original/image-20170201-12685-1l79wjf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=353&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/155148/original/image-20170201-12685-1l79wjf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=444&fit=crop&dpr=1 754w, https://images.theconversation.com/files/155148/original/image-20170201-12685-1l79wjf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=444&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/155148/original/image-20170201-12685-1l79wjf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=444&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Jun Wu (front) and Juan Carlos Izpisua Belmonte, who led the team that developed the human-animal chimeras.</span>
<span class="attribution"><span class="source">Salk Institute</span></span>
</figcaption>
</figure>
<h2>Potent cells</h2>
<p>The chimeric pig foetuses produced by <a href="http://www.salk.edu/scientist/juan-carlos-izpisua-belmonte/">Juan Izpisua Belmonte</a>, <a href="http://belmonte.salk.edu/people.php">Jun Wu</a> and their team at the Salk Institute were not allowed to develop to term, and contained human cells in multiple tissues.</p>
<p>The actual proportion of human cells in the chimeras was quite low and their presence appeared to interfere with development. Even so, the study represents a first step in a new avenue of stem cell research which has great promise. But it also raises serious ethical concerns.</p>
<p>A chimera is an organism containing cells from two or more individuals and they do occur in nature, albeit rarely. </p>
<p>Marmoset monkeys often display chimerism in their blood and other tissues as a result of transfer of cells between twins while still in the womb. Following a successful bone marrow transplantation to treat leukaemia, patients have cells in their bone marrow from the donor as well as themselves.</p>
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<p>Chimeras can be generated artificially in the laboratory through combining the cells from early embryos of the same or different species. The creation of <a href="http://dev.biologists.org/content/130/25/6155">chimeric mice</a> has been essential for research in developmental biology, genetics, physiology and pathology. </p>
<p>This has been made possible by advances in gene targeting in mouse embryonic stem cells, allowing scientists to alter the cells to express or silence certain genes. Along with the ability to use those cells in the development of chimeras, this has enabled researchers to produce animals that can be used to study how genes influence health and disease. </p>
<p>The pioneers of this technology are Oliver Smithies, Mario Cappechi and Martin Evans, who received a <a href="http://www.nobelprize.org/nobel_prizes/medicine/laureates/2007/">Nobel Prize in Physiology or Medicine in 2007</a> for their work. </p>
<p>More recently, researchers have become interested in investigating the ability of human <a href="http://stemcell.childrenshospital.org/about-stem-cells/pluripotent-stem-cells-101/">pluripotent stem cells</a> – “master cells” – obtained from human embryos or created in the laboratory from body cells, to contribute to the tissues of chimeric animals.</p>
<p>Human pluripotent stem cells can be grown indefinitely in the laboratory, and like their mouse counterparts, they can form all the tissues of the body. </p>
<p>Many researchers have now shown they can make functional human tissues of medical significance from human pluripotent cells, such as nerve, heart, liver and kidney cells. </p>
<p>Indeed, cellular therapeutics derived from human pluripotent stem cells are already in <a href="http://www.nature.com/nrm/journal/v17/n3/full/nrm.2016.10.html">clinical trials</a> for spinal cord injury, diabetes and macular degeneration.</p>
<p>However, since 2007 it has been clear that there is not one type of pluripotent stem cell. Rather, a range of different types of pluripotent stem cells have been generated in mice and humans using different techniques. </p>
<p>These cells appear to correspond to cells at different stages of embryonic development, and therefore are likely to have different properties, raising the question about which source of cells is best.</p>
<p>Creating a chimeras has long been the gold standard used by researchers to determine the potential of pluripotent stem cells. While used extensively in animal stem cell research, chimeric studies using human pluripotent stem cells have proved challenging as few human cells survive in human-animal chimeras.</p>
<h2>Medical possibilities</h2>
<p>Although the number of human cells in the chimera was low, the findings by the Salk Institute researchers provide a new avenue to address two important goals. The first is the possibility of creating “humanised” animals for use in biomedical research. </p>
<p>While it is already possible to produce mice with human blood, providing an invaluable insight into how our blood and immune system functions, these animals rely on the use of human fetal tissue and are difficult to make. </p>
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<span class="caption">Human iPS cells (green) contributed to a developing heart of four-week-old pig embryo.</span>
<span class="attribution"><span class="source">Salk Institute</span></span>
</figcaption>
</figure>
<p>The use of pluripotent stem cells in human-animal chimeras might facilitate the efficient production of mice with human blood cells, or other tissues such as liver or heart, on a larger scale. This could greatly enhance our ability to study the development of diseases and to develop new drugs to treat them.</p>
<p>The second potential application of human-animal chimeras comes from some <a href="http://www.sciencedirect.com/science/article/pii/S0092867410008433">enticing studies</a> performed in Japan in 2010. These studies were able to generate interspecies chimeras following the introduction of rat pluripotent stem cells into a mouse embryo that lacked a key gene for pancreas development. </p>
<p>As a result, the live born mice had a fully functional pancreas comprised entirely of rat cells. If a similar outcome could be achieved with human stem cells in a pig chimera, this would represent a new source of human organs for transplantation.</p>
<h2>Ethical boundaries</h2>
<p>While scientifically achieving such goals remains a long way off, it is almost certain that progress in pluripotent stem cell biology will enable successful experimentation along these lines. But how much of this work is ethically acceptable, and where do the boundaries lie?</p>
<p>Many people condone the use of pigs for food or as a source of replacement heart valves. They might also be content to use pig embryos and foetuses as incubators to manufacture human pancreas or hearts for those waiting on the transplant list. But the use of human-monkey chimeras may be more contested.</p>
<p>Studies have shown that early cells of the central nervous system made from human embryonic stem cells can <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735209/">engraft and colonise the brain</a> of a newborn mouse. This provides a proof of concept for possible cellular therapies. </p>
<p>But what if human cells were injected into monkey embryos? What would be the ethical and cognitive status of a newborn rhesus monkey whose brain consists of predominantly human nerves?</p>
<p>It may be possible to genetically engineer the cells so that human cells can effectively grow into replacement parts. But what safeguards do we need to ensure that the human cells don’t also contribute to other organs of the host, such as the reproductive organs?</p>
<p>While the announcement of a human-pig chimera may have taken many by surprise, regulators and medical researchers well recognise that chimeric research may raise issues in addition to the those <a href="https://theconversation.com/we-mightnt-like-it-but-there-are-ethical-reasons-to-use-animals-in-medical-research-58878">already posed by animal research</a>.</p>
<p>However, rather than call for a blanket ban or restricting funding for this area of medical research, it requires careful case-by-case consideration by independent oversight committees fully aware of animal welfare considerations and recognising existing standards. </p>
<p>For example, The <a href="http://www.isscr.org/docs/default-source/guidelines/isscr-guidelines-for-stem-cell-research-and-clinical-translation.pdf">2016 Guidelines for Clinical Research and Translation</a> from the International Society for Stem Cell Research call for research where human gametes could be generated from human-animal chimeras to be prohibited, but supports research using human-animal chimeras conducted under appropriate review and oversight.</p>
<p>Chimeric research will and needs to continue. But equally scientists involved in this field need to continue to discuss and consider the implications of their research with the broader community. Chimeras can all too readily be dismissed as mythological monsters engendering fear.</p><img src="https://counter.theconversation.com/content/72179/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Martin Pera receives funding from the Australian Research Council and the National Health and Medical Research Council.</span></em></p><p class="fine-print"><em><span>Megan Munsie receives funding from the Australian Research Council. She is affiliated with the International Society for Stem Cell Research, Australasian Society for Stem Cell Research and International Society for Cell Therapy. </span></em></p>Human-animal hybrids - or ‘chimeras’ - might sound strange, but they offer great hope for new life saving therapies, as long as key ethical boundaries are respected.Martin Pera, Professor and Former Program Leader of Stem Cells Australia, The University of MelbourneMegan Munsie, Head of Education, Ethics, Law & Community Awareness Unit, Stem Cells Australia, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.