tag:theconversation.com,2011:/au/topics/xenotransplantation-23110/articlesXenotransplantation – The Conversation2024-03-27T19:07:40Ztag:theconversation.com,2011:article/2263932024-03-27T19:07:40Z2024-03-27T19:07:40ZThe first pig kidney has been transplanted into a living person. But we’re still a long way from solving organ shortages<figure><img src="https://images.theconversation.com/files/584634/original/file-20240327-22-zkx0ie.jpg?ixlib=rb-1.1.0&rect=0%2C73%2C8192%2C5383&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.massgeneral.org/news/press-release/worlds-first-genetically-edited-pig-kidney-transplant-into-living-recipient">Massachusetts General Hospital</a></span></figcaption></figure><p>In a world first, we heard last week that US surgeons had transplanted a kidney from a gene-edited pig into a living human. News reports said the procedure was <a href="https://www.npr.org/sections/health-shots/2024/03/21/1239790816/first-pig-kidney-human-transplant">a breakthrough</a> in xenotransplantation – when an organ, cells or tissues are transplanted from one species to another.</p>
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<figcaption><span class="caption">The world’s first transplant of a gene-edited pig kidney into a live human was announced last week.</span></figcaption>
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<p>Champions of xenotransplantation regard it as <em>the</em> solution to organ shortages across the world. In December 2023, <a href="https://www.anzdata.org.au/anzod/publications-2/organ-waiting-list/">1,445 people</a> in Australia were on the waiting list for donor kidneys. In the United States, more than <a href="https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/">89,000</a> are waiting for kidneys. </p>
<p>One biotech CEO says gene-edited pigs <a href="https://www.technologyreview.com/2015/08/12/248193/surgeons-smash-records-with-pig-to-primate-organ-transplants/">promise</a> “an unlimited supply of transplantable organs”.</p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6452271/">Not</a>, <a href="https://theconversation.com/organ-transplants-from-pigs-medical-miracle-or-pandemic-in-the-making-175290">everyone</a>, though, <a href="https://onlinelibrary.wiley.com/doi/10.1111/imj.13183">is convinced</a> transplanting animal organs into humans is really the answer to organ shortages, or even if it’s right to use organs from other animals this way.</p>
<p>There are two critical barriers to the procedure’s success: organ rejection and the transmission of <a href="https://journals.sagepub.com/doi/epdf/10.1177/09636897241226849">animal viruses to recipients</a>. </p>
<p>But in the past decade, a new platform and technique known as CRISPR/Cas9 – often shortened to CRISPR – has promised to mitigate these issues.</p>
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Read more:
<a href="https://theconversation.com/organ-transplants-from-pigs-medical-miracle-or-pandemic-in-the-making-175290">Organ transplants from pigs: Medical miracle or pandemic in the making?</a>
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<h2>What is CRISPR?</h2>
<p>CRISPR gene editing takes advantage of a system already found in nature. CRISPR’s “genetic scissors” evolved in bacteria and other microbes to help them fend off viruses. Their cellular machinery <a href="https://www.sciencedirect.com/science/article/pii/S0300908415001042#:%7E:text=The%20system%2C%20called%20CRISPR%2DCas,remember%2C%20recognize%20and%20clear%20infections.">allows them</a> to integrate and ultimately destroy viral DNA by cutting it.</p>
<p>In 2012, two teams of scientists <a href="https://www.science.org/doi/10.1126/science.1225829">discovered how to harness</a> this bacterial immune system. This is made up of repeating arrays of DNA and associated proteins, known as “Cas” (CRISPR-associated) proteins. </p>
<p>When they used a particular Cas protein (Cas9) with a “guide RNA” made up of a singular molecule, they found they could <a href="https://pubmed.ncbi.nlm.nih.gov/22745249/">program</a> the CRISPR/Cas9 complex to break and repair DNA at precise locations as they desired. The system could even “knock in” new genes at the repair site. </p>
<p>In 2020, the two scientists leading these teams were awarded a <a href="https://www.nobelprize.org/prizes/chemistry/2020/summary/">Nobel prize</a> for their work.</p>
<p>In the case of the latest xenotransplantation, CRISPR technology was used to <a href="https://www.massgeneral.org/news/press-release/worlds-first-genetically-edited-pig-kidney-transplant-into-living-recipient">edit 69 genes</a> in the donor pig to inactivate viral genes, “humanise” the pig with human genes, and knock out harmful pig genes.</p>
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<figcaption><span class="caption">How does CRISPR work?</span></figcaption>
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Read more:
<a href="https://theconversation.com/what-is-crispr-the-gene-editing-technology-that-won-the-chemistry-nobel-prize-147695">What is CRISPR, the gene editing technology that won the Chemistry Nobel prize?</a>
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<h2>A busy time for gene-edited xenotransplantation</h2>
<p>While CRISPR editing has brought new hope to the possibility of xenotransplantation, even recent trials show great caution is still warranted.</p>
<p>In 2022 and 2023, two patients with <a href="https://www.medschool.umaryland.edu/news/2023/um-medicine-faculty-scientists-and-clinicians-perform-second-historic-transplant-of-pig-heart-into-patient-with-end-stage-cardiovascular-disease.html#:%7E:text=The%20first%20historic%20surgery%2C%20performed,had%20end%2Dstage%20heart%20disease.">terminal heart diseases</a>, who were ineligible for traditional heart transplants, were granted <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00775-4/abstract">regulatory permission</a> to receive a gene-edited pig heart. These pig hearts had ten genome edits to make them more suitable for transplanting into humans. However, both patients died within several weeks of the procedures. </p>
<p>Earlier this month, we heard a team of surgeons in China transplanted a gene-edited pig liver into a <a href="https://www.nature.com/articles/d41586-024-00853-8">clinically dead man</a> (with family consent). The liver functioned well up until the ten-day limit of the trial.</p>
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Read more:
<a href="https://theconversation.com/you-donate-your-body-to-science-you-die-what-happens-next-1481">You donate your body to science, you die ... what happens next?</a>
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<h2>How is this latest example different?</h2>
<p>The gene-edited pig kidney <a href="https://www.massgeneral.org/news/kidney-xenotransplant-faqs">was transplanted</a> into a relatively young, living, legally competent and consenting adult.</p>
<p>The total number of gene edits edits made to the donor pig is very high. The researchers report making <a href="https://www.nature.com/articles/d41586-024-00879-y">69 edits</a> to inactivate viral genes, “humanise” the pig with human genes, and to knockout harmful pig genes.</p>
<p>Clearly, the race to transform these organs into viable products for transplantation is ramping up.</p>
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Read more:
<a href="https://theconversation.com/what-are-uterus-transplants-who-donates-their-uterus-and-what-are-the-risks-190443">What are uterus transplants? Who donates their uterus? And what are the risks?</a>
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<h2>From biotech dream to clinical reality</h2>
<p>Only a few months ago, CRISPR gene editing made its debut in mainstream medicine. </p>
<p>In November, drug regulators in the <a href="https://www.gov.uk/government/news/mhra-authorises-world-first-gene-therapy-that-aims-to-cure-sickle-cell-disease-and-transfusion-dependent-thalassemia">United Kingdom</a> and <a href="https://www.fda.gov/media/174618/download?attachment">US</a> approved the world’s first CRISPR-based genome-editing therapy for human use – a treatment for life-threatening forms of sickle-cell disease. </p>
<p>The treatment, known as <a href="https://sicklecellanemianews.com/ctx001-sickle-cell-disease">Casgevy</a>, uses CRISPR/Cas-9 to edit the patient’s own blood (bone-marrow) stem cells. By disrupting the <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2029392">unhealthy gene</a> that gives red blood cells their “sickle” shape, the aim is to produce red blood cells with a healthy spherical shape. </p>
<p>Although the treatment uses the patient’s own cells, the same underlying principle applies to recent clinical xenotransplants: unsuitable cellular materials may be edited to make them therapeutically beneficial in the patient.</p>
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<a href="https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Sickle cells have a different shape to healthy round red blood cells" src="https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=337&fit=crop&dpr=1 600w, https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=337&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=337&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/584639/original/file-20240327-26-b7jv5t.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">CRISPR technology is aiming to restore diseased red blood cells to their healthy round shape.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-rendered-medical-illustration-sickle-cell-2221001799">Sebastian Kaulitzki/Shutterstock</a></span>
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<a href="https://theconversation.com/organs-too-risky-to-donate-may-be-safer-than-we-think-we-crunched-the-numbers-and-heres-what-we-found-124993">Organs 'too risky' to donate may be safer than we think. We crunched the numbers and here's what we found</a>
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<h2>We’ll be talking more about gene-editing</h2>
<p>Medicine and gene technology regulators are increasingly asked to <a href="https://www.utas.edu.au/__data/assets/pdf_file/0011/1634258/OP12-final-report.pdf">approve new experimental trials</a> using gene editing and CRISPR.</p>
<p>However, neither xenotransplantation nor the therapeutic applications of this technology lead to changes to the genome that can be inherited.</p>
<p>For this to occur, CRISPR edits would need to be applied to the cells at the earliest stages of their life, such as to <a href="https://doi.org/10.1089/crispr.2020.0082">early-stage embryonic cells</a> in vitro (in the lab). </p>
<p>In Australia, intentionally creating heritable alterations to the human genome is a criminal offence carrying <a href="https://classic.austlii.edu.au/au/legis/cth/consol_act/pohcfra2002465/s15.html">15 years’ imprisonment</a>. </p>
<p><a href="https://www.utas.edu.au/__data/assets/pdf_file/0011/1634258/OP12-final-report.pdf">No jurisdiction in the world</a> has laws that <a href="https://doi.org/10.1089/crispr.2020.0082">expressly permits</a> heritable human genome editing. However, some <a href="https://crispr-gene-editing-regs-tracker.geneticliteracyproject.org/russia-germline-embryonic/">countries</a> lack specific regulations about the procedure.</p>
<h2>Is this the future?</h2>
<p>Even without creating inheritable gene changes, however, xenotransplantation using CRISPR is in its infancy.</p>
<p>For all the promise of the headlines, there is not yet one example of a stable xenotransplantation in a living human lasting <a href="https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.03060/full">beyond seven months</a>. </p>
<p>While authorisation for this recent US transplant has been granted under the so-called “compassionate use” <a href="https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=312.310">exemption</a>, conventional clinical trials of pig-human xenotransplantation have yet to commence. </p>
<p>But the prospect of such trials would likely require significant improvements in current outcomes to gain regulatory approval <a href="https://www.fda.gov/media/102126/download">in the US</a> or <a href="https://iris.who.int/bitstream/handle/10665/341817/WHO-HTP-EHT-CPR-2011.01-eng.pdf?sequence=1&isAllowed=y">elsewhere</a>. </p>
<p>By the same token, regulatory approval of any “off-the-shelf” xenotransplantation organs, including gene-edited kidneys, would seem <a href="https://link.springer.com/chapter/10.1007/978-981-99-7691-1_24">some way off</a>.</p><img src="https://counter.theconversation.com/content/226393/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Christopher Rudge was a member of a research team that designed and convened an Australian citizens' jury on genome editing in 2021-22. This was funded by the Medical Research Future Fund.</span></em></p>Champions of xenotransplantation see it as the solution to organ shortages across the world. But this technology has other applications.Christopher Rudge, Law lecturer, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1826242022-05-10T18:25:19Z2022-05-10T18:25:19ZPig-human transplants may be a misguided attempt to address the organ shortage<figure><img src="https://images.theconversation.com/files/461887/original/file-20220509-20-agjzud.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C6000%2C4500&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Cross-species transplants require us to examine the relationships between humans and animals.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><iframe style="width: 100%; height: 100px; border: none; position: relative; z-index: 1;" allowtransparency="" allow="clipboard-read; clipboard-write" src="https://narrations.ad-auris.com/widget/the-conversation-canada/pig-human-transplants-may-be-a-misguided-attempt-to-address-the-organ-shortage" width="100%" height="400"></iframe>
<p>At the end of 2021, 57-year old David Bennett Sr. was bedridden and on life-support with irreversible heart failure. He was not eligible for a human heart transplant or an implanted mechanical heart pump because of his underlying health condition and, allegedly, “<a href="https://www.technologyreview.com/2022/05/04/1051725/xenotransplant-patient-died-received-heart-infected-with-pig-virus/">a history of disregarding medical advice</a>.”</p>
<p>Certain death was on the horizon and this fatal prognosis made Bennett a candidate for a highly experimental and never-before-attempted surgical procedure involving the transplantation of a heart from a genetically modified pig.</p>
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Read more:
<a href="https://theconversation.com/pig-heart-transplant-was-david-bennett-the-right-person-to-receive-groundbreaking-surgery-174991">Pig heart transplant: was David Bennett the right person to receive groundbreaking surgery?</a>
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<p>The pig-to-human cardiac transplant — or xenotransplant — was <a href="https://www.technologyreview.com/2022/01/11/1043374/gene-edited-pigs-heart-transplant/">authorized by the U.S. Food and Drug Administration on compassionate grounds on New Year’s Eve 2021</a> and the surgery was performed on Jan. 7, 2022.</p>
<p>Initial reports following the experimental surgery suggested that <a href="https://doi.org/10.1038/d41586-022-00111-9">the genetically modified, human-compatible pig heart was functioning well and infection was not a problem</a>. </p>
<p>Bennett died on March 8 — at the time, “no obvious cause” of death was identified. Now, it has been reported that the pig heart was <a href="https://www.newscientist.com/article/2319108-man-who-received-pig-heart-transplant-has-died-after-pig-virus-found/">infected with a virus called porcine cytomegalovirus and that this virus may have contributed to Bennett’s death</a>. </p>
<p>Though the cause of death remains unclear, infection has been implicated in previous xenotransplantation failures involving baboons as the recipients.</p>
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<figcaption><span class="caption">The BBC reports on the initial pig-to-human heart transplant surgery.</span></figcaption>
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<h2>More demand than supply</h2>
<p>There is an ongoing chronic <a href="https://hillnotes.ca/2021/04/16/organ-donation-in-canada-2/">shortage of suitable human organs for life-saving transplantation</a>. Indeed, many <a href="https://www.cihi.ca/en/organ-transplants-in-canada-2020-donations-and-need-infographic">Canadian transplant candidates die waiting for an organ donation</a>.</p>
<p>Attempts to increase the limited supply of human organs have included changes to consent rules: <a href="https://doi.org/10.1016/S2468-1253(17)30037-7">moving to an opt-out system</a>, <a href="https://doi.org/10.1016/S0140-6736(18)31870-1">introducing directed living donation and deceased donor-initiated chains</a> and, in some countries, <a href="https://doi.org/10.1097/MOT.0000000000000617">offering financial compensation</a>. </p>
<p>Still, patients die on transplant waiting lists. For this reason, there is ever increasing interest in xenotransplantation — an ethically controversial practice. </p>
<h2>Nonhuman primates and pigs</h2>
<p>In 1984, <a href="https://time.com/4086900/baby-fae-history/">the heart of a young baboon was transplanted into Baby Fae</a>, an infant born with a fatal heart defect called <a href="https://www.mayoclinic.org/diseases-conditions/hypoplastic-left-heart-syndrome/symptoms-causes/syc-20350599">hypoplastic left heart syndrome</a>. Baby Fae lived for three weeks, but eventually died of heart failure caused by rejection of the transplanted baboon heart.</p>
<p>Prior to this, there had been three other experimental nonhuman heart transplants, <a href="https://dx.doi.org/10.1080/08998280.2012.11928783">the earliest in 1964 using a chimpanzee heart</a>.</p>
<p>More recent efforts at xenotransplantation have involved the <a href="https://www.uab.edu/news/campus/item/12566-uab-announces-first-clinical-grade-transplant-of-gene-edited-pig-kidneys-into-brain-dead-human">transplantation of pig kidneys into brain-dead humans</a>. The most dramatic recent example, however, remains Bennett’s first-in-human cardiac xenotransplant using a genetically modified pig heart.</p>
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<span class="caption">One of the earliest xenotransplants involved a baboon heart transplanted into an infant.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
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<p>For some, the use of pig hearts for xenotransplantation may be ethically preferable to the use of nonhuman primate hearts because pigs are already used for medicine: for example, <a href="https://www.npr.org/2021/10/20/1047560631/in-a-major-scientific-advance-a-pig-kidney-is-successfully-transplanted-into-a-h">pig heart valves, corneas and skin are used in various treatments</a>.</p>
<p>Or it could be that pigs are preferable “organ donors” because they are already used for food. When it comes to food animals — those who are consumed by humans — people can be biased against accurately seeing the subjectivity of the animal. This is referred to as the “<a href="https://dx.doi.org/10.3390/ani9121125">meat paradox</a>,” where people perceive food animals as “<a href="https://www.bbc.com/future/article/20190206-what-the-meat-paradox-reveals-about-moral-decision-making">objects and thereby avoid the discomfort caused by knowing about the suffering behind consumer goods</a>.”</p>
<p>A third reason to prefer killing pigs for human benefit instead of killing nonhuman primates is that pigs are biologically less similar to humans.</p>
<h2>Prioritizing humans</h2>
<p>Moral worth — <a href="https://impactethics.ca/2014/09/05/which-lives-are-you-pro/">the value assigned to others in ways that affect how we treat them</a> — is not species specific. Rather, it is associated with specific capacities such as the ability to think, make choices, experience pain, communicate and have social relationships.</p>
<p>Because a human zygote lacks such capacities, not many believe that they have the same moral worth as a human two-year old, and there is nothing obviously irrational about this belief. Though a zygote may have the potential to reach a comparable level of development as a two-year old, they are not yet comparable. Their shared human identity is beside the point. </p>
<p>On occasion, humans may choose to prioritize the interests of their companion animals without doing something obviously wrong. For example, it is not irrational to spend money on the care of pets, even if that money could have gone towards helping fellow humans. This choice may reflect a shared social relationship and the emotional bonds that come with it. It may also reflect a sense of duty toward nonhuman animals that are dependent on the care provided by humans. </p>
<p>Having said this, clearly, there are times when it is appropriate to prioritize the interests of humans over other animals; it is just that <a href="https://aeon.co/essays/human-exceptionalism-is-a-danger-to-all-human-and-nonhuman">this perspective shouldn’t be the default position</a>. In any case, it is not clear, nor is it easy to determine, that Bennett’s extraordinary xenotransplant falls into this category.</p>
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<a href="https://images.theconversation.com/files/462152/original/file-20220510-16-xxiv1e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="pigs standing at a trough in a shed" src="https://images.theconversation.com/files/462152/original/file-20220510-16-xxiv1e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/462152/original/file-20220510-16-xxiv1e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/462152/original/file-20220510-16-xxiv1e.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/462152/original/file-20220510-16-xxiv1e.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/462152/original/file-20220510-16-xxiv1e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/462152/original/file-20220510-16-xxiv1e.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/462152/original/file-20220510-16-xxiv1e.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The killing and consumption of pigs is normalized as they are produced for food.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<h2>Animal welfare</h2>
<p>In Canada, support for animal-based research is anchored in a commitment to <a href="https://www.ccac.ca/Documents/2013_National_Survey.pdf">prevent — or at the very least reduce — unnecessary suffering</a>. The problem with this stance is that current animal welfare considerations do not typically support strong constraints on the scientific use of animals. </p>
<p>Notably, there are pressures to limit, but <a href="https://ccac.ca/en/facts-and-legislation/animal-data/annual-animal-data-reports.html">not to eliminate</a>, the use of animals in research likely to have severe welfare impacts. Also, common animal welfare considerations do not prohibit killing the animals, they just constrain how they are killed. </p>
<p>Part of the problem here is that there are <a href="https://doi.org/10.1017/S0963180119000732">no substantive ethical principles governing animal use in science</a>. The three Rs, which are pervasive in regulated animal use in science, emphasize <em>replacing</em> sentient animals (animals capable of experiencing pain and pleasure) where possible, <em>reducing</em> the number of sentient animals used in studies to a “bare minimum” and <em>refining</em> their experiences of use to minimize suffering. </p>
<p>As such, the three Rs seem to assume something like a principled commitment to non-maleficence — <a href="https://doi.org/10.1093/ilar/ilaa014">avoiding unnecessary harm</a>. However, the continued dependency on harmful animal-based research that almost always ends with the killing of the animals belies this claim, given the known <a href="https://www.cbc.ca/radio/quirks/may-7-endangered-tiny-porpoise-mars-quakes-thermal-batteries-and-more-1.6443011/meet-the-canadian-researcher-determined-to-take-the-animals-out-of-lab-testing-1.6443917">significant problems of extrapolation of research findings</a>.</p>
<p>Given the ethical challenges with animal-based research in general and more specifically the ethical challenges with animal-to-human xenotransplantation, there is good reason to look for <a href="https://www.thehastingscenter.org/xenotransplantation-three-areas-of-concern/">other strategies to increase the supply of organs</a> for transplantation.</p><img src="https://counter.theconversation.com/content/182624/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andrew Fenton is a member of the (Canadian) Society for Humane Science and is currently serving on a subcommittee for the Canadian Council on Animal Care (revising their core ethics document) and a panel on nonhuman primate research for the National Anti-Vivisection Society. </span></em></p><p class="fine-print"><em><span>Françoise Baylis 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 heart used in the first pig-human transplant was infected with a pig virus. This reveals that using other species as organ donors may not provide a solution for organ shortages.Françoise Baylis, University Research Professor, Philosophy, Dalhousie UniversityAndrew Fenton, Associate Professor, Philosophy, Dalhousie UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1758932022-03-11T13:19:38Z2022-03-11T13:19:38ZOrgans from genetically engineered pigs may help shorten the transplant wait list<figure><img src="https://images.theconversation.com/files/451412/original/file-20220310-17-1rk65gg.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1024%2C683&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Xenotransplantation has made significant strides over the past few decades.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/xenotransplant-drawing-news-photo/179793591">BSIP/Universal Images Group via Getty Images</a></span></figcaption></figure><p>Demand for life-saving organ transplantation is at an all-time high. In 2021, a record <a href="https://unos.org/news/2021-all-time-records-organ-transplants-deceased-donor-donation/">41,000-plus</a> organ transplants were performed in the U.S., with top numbers for kidney, liver and heart transplants. But a limited supply of donor organs remains an ongoing problem. Currently <a href="https://optn.transplant.hrsa.gov/data/">over 100,000</a> people are on the transplant wait list in the U.S., and many more are unable to get on the list because of <a href="https://optn.transplant.hrsa.gov/professionals/by-topic/ethical-considerations/general-considerations-in-assessment-for-transplant-candidacy/">strict eligibility requirements</a> and <a href="https://doi.org/10.1001/jama.2017.19152">racial</a> <a href="https://doi.org/10.1001/jamanetworkopen.2020.34630">disparities</a> in access.</p>
<p>As a <a href="http://www.ctsurgery.pitt.edu/person/david-j-kaczorowski-md">cardiac transplant surgeon</a>, I have personally witnessed the tragedy of this shortage of donor organs. But I have also seen the potential of one possible solution to this problem: <a href="https://www.fda.gov/vaccines-blood-biologics/xenotransplantation">xenotransplantation</a>, or transplanting animal organs into human beings.</p>
<p>In <a href="https://www.scientificamerican.com/article/pig-kidneys-transplanted-to-human-in-milestone-experiment/">September 2021</a>, researchers successfully transplanted two genetically engineered pig kidneys into a brain-dead patient. And in January 2022, I was <a href="https://mirm-pitt.net/tissue-engineering/dr-david-kaczorowski-member-of-surgical-team-on-historic-first-successful-transplant-of-porcine-heart-into-adult-human-with-end-stage-heart-disease/">part of the surgical team</a> that conducted the <a href="https://www.nytimes.com/2022/01/10/health/heart-transplant-pig-bennett.html">first pig-to-human heart transplant</a> in a living patient. Recent news about the <a href="https://www.nytimes.com/2022/03/09/health/heart-transplant-pig-bennett.html">patient’s death</a> two months after the procedure is sobering, but researchers like me remain optimistic. While much work still needs to be done, these successes point to how far science has come toward making animal-to-human transplants a viable treatment possibility.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/Wqf3PXUngsE?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The man who received the first pig heart transplant died on March 8, 2022, two months after the procedure.</span></figcaption>
</figure>
<h2>Early attempts</h2>
<p>While animal-to-human transplants have attracted considerable attention recently, many attempts have been made to transplant animal cells, tissues and organs into humans over the past 60 years, with varying degrees of success. </p>
<p>In the 1960s, kidney transplantation was not broadly practiced because of a <a href="https://doi.org/10.1093/bja/aer384">lack of donor organs</a>. <a href="https://doi.org/10.1093/ilar.37.1.9">Ethical and legal concerns</a> made it difficult to obtain live donors, and organs collected from deceased donors did not meet much success.</p>
<p>So a surgeon named Keith Reemtsma performed a <a href="https://doi.org/10.1111/j.1749-6632.1969.tb56392.x">series of 12 kidney transplants</a> using chimpanzees as donors. While most of the transplanted organs – and thus the human patients – survived for only a few weeks, one of the patients survived for nine months. Infection was the major issue in half of the patients, while irreversible organ rejection occurred in the other half. </p>
<p>Thomas Starzl is another surgeon who attempted animal-to-human organ transplants. He performed a similar <a href="https://doi.org/10.1097/00007890-196411000-00009">series of kidney</a> transplants around the same time as Reemtsma using baboons as donors, with the organs surviving up to two months. He’s most known for his <a href="https://doi.org/10.1111/xen.12306">liver transplants</a>, with three attempts using chimpanzee livers from 1966 to 1974 that lasted from 24 hours to less than 14 days. In the early 1990s, his two baboon liver transplants lasted for 26 and 70 days. While one of the baboon livers functioned well, the patient ultimately died from overwhelming infection. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/451410/original/file-20220310-19-1vyj5ez.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="An infant lies in incubator, with her head cradled in an adult's hand." src="https://images.theconversation.com/files/451410/original/file-20220310-19-1vyj5ez.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/451410/original/file-20220310-19-1vyj5ez.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=614&fit=crop&dpr=1 600w, https://images.theconversation.com/files/451410/original/file-20220310-19-1vyj5ez.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=614&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/451410/original/file-20220310-19-1vyj5ez.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=614&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/451410/original/file-20220310-19-1vyj5ez.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=771&fit=crop&dpr=1 754w, https://images.theconversation.com/files/451410/original/file-20220310-19-1vyj5ez.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=771&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/451410/original/file-20220310-19-1vyj5ez.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=771&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Baby Fae was the first successful infant xenotransplant, surviving for 20 days with a baboon heart.</span>
<span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/BabyFae/a7e818231958441696f356ee12594a95">AP Photo/Duane R. Miller</a></span>
</figcaption>
</figure>
<p>Doctors have also made attempts to transplant animal hearts, the first of which predated the first human-to-human heart transplant. In 1964, a <a href="https://doi.org/10.1001/jama.1964.03060390034008">chimpanzee heart</a> transplanted by James Hardy survived for only a few hours. Len Bailey’s 1983 attempt at transplanting a <a href="https://doi.org/10.1001/jama.1985.03360230053022">baboon heart</a> into an infant known as <a href="https://time.com/4086900/baby-fae-history/">Baby Fae</a> prolonged her life for 20 days, a record at the time.</p>
<h2>Overcoming barriers</h2>
<p>While these early results may seem poor at first glance, a number of these transplants actually lasted longer than many <a href="https://doi.org/10.5772/940">early human-to-human kidney transplants</a>. The first patient to receive a donated kidney lasted for only four days in 1933, and later attempts in the 1940s and 1950s yielded similar results. Immunosuppressing drugs that prevent the immune system from attacking donor organs also weren’t available at the time of these early attempts at xenotransplantation, pointing to the promise of these procedures as science advanced. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/dCSiTpnNrMQ?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">A pig heart under examination by researchers at the University of Pittsburgh.</span></figcaption>
</figure>
<p>But transplanting organs across species faces a number of obstacles, the most integral of which is evolution. As species grow apart, <a href="https://doi.org/10.1016/S1074-7613(01)00124-8">increasing differences</a> in their molecular makeup can result in incompatibilities that make cross-species transplant difficult or impossible. Among the most problematic are differences in immunity, inflammation and blood clotting that damage both the transplanted organs and the host’s body.</p>
<p>The similarity of <a href="https://doi.org/10.1080/08998280.2000.11927634">nonhuman primates</a> like chimpanzees and baboons to humans, both in anatomy and in their immune systems, made them appealing donors for early transplants. But their strong similarities to people also raised ethical concerns that dissuaded some physicians like Starzl from using them as donors.</p>
<p>On the other hand, <a href="https://doi.org/10.1080/08998280.2000.11927634">pigs offer a potentially better source</a> of donor organs. Compared with nonhuman primates, pigs mature much more quickly and produce more offspring. They are also a common source of food for people, and their tissues are already used for prosthetic heart valves and other medical treatments.</p>
<p>While <a href="https://doi.org/10.1016/j.ijsu.2015.06.060">pig-to-human transplants</a> have also been attempted in the past, 80 million years of evolution stood in the way. Pigs have <a href="https://doi.org/10.1080/08998280.2000.11927634">molecules</a> on the surfaces of their cells that humans do not. If these molecules are introduced into a person’s body, their human immune system will register them as foreign and mount an attack. This process, called <a href="https://medlineplus.gov/ency/article/000815.htm">hyperacute rejection</a>, is a central reason many transplanted animal organs fail.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/xgBnYr0_FRk?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Genetically engineering pigs to be more compatible with humans could help reduce the risk of organ rejection.</span></figcaption>
</figure>
<p>A number of advances that reduce these incompatibilities have helped overcome the problem of hyperacute rejection. <a href="https://doi.org/10.1126/science.1078942">Genetically engineered pigs</a> without the genes that produce the foreign molecules triggering rejection and with additional <a href="https://doi.org/10.1002/mrd.21127">human genes</a> that help the recipient’s body accept the new organ are one key improvement. The <a href="https://www.nytimes.com/2022/01/10/health/heart-transplant-pig-bennett.html">pig heart</a> my team and I transplanted this year was genetically engineered, as were the <a href="https://www.nytimes.com/2021/10/19/health/kidney-transplant-pig-human.html">pig kidneys</a> from late 2021. There have also been improvements in medications that <a href="https://doi.org/10.1038/ncomms11138">suppress the immune system</a> of the recipient so it’s less likely to mount an attack against the organ.</p>
<h2>Looking forward</h2>
<p>Recent successes with genetically engineered pig transplants make clear that xenotransplantation is no longer a dream from a distant future but something becoming increasingly achievable by modern medicine.</p>
<p>But many questions still remain. What is the best way to suppress a recipient’s immune system so the transplanted organ survives but the risk of infection stays low? Can animal organs be tailored to individuals to minimize rejection? How can animal organs be better preserved and distributed? </p>
<p>Answering these and many other questions will be key to realizing the therapeutic potential of xenotransplantation, and helping the hundreds of thousands of people waiting for an organ.</p>
<p>[<em><a href="https://memberservices.theconversation.com/newsletters?nl=science&source=inline-science-corona-important">Get The Conversation’s most important coronavirus headlines, weekly in a science newsletter</a></em>]</p><img src="https://counter.theconversation.com/content/175893/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>David Kaczorowski has previously received research funding through a grant from United Therapeutics. </span></em></p>Recent successes putting genetically modified pig organs into people have brought xenotransplantation back into the spotlight.David Kaczorowski, Associate Professor of Cardiothoracic Surgery, University of PittsburghLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1752902022-02-27T13:08:39Z2022-02-27T13:08:39ZOrgan transplants from pigs: Medical miracle or pandemic in the making?<figure><img src="https://images.theconversation.com/files/447227/original/file-20220218-3064-xtzvrp.jpg?ixlib=rb-1.1.0&rect=422%2C35%2C4922%2C3332&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Xenotransplantation is the transplanting of cells, tissues or organs from animals to humans. Pre-clinical trials of organ transplant from pigs have addressed some of the technical barriers.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>Three out of four <a href="https://www.cdc.gov/onehealth/basics/zoonotic-diseases.html">new diseases are zoonotic</a>, meaning they have evolved to infect new host species. For example, a mutated <a href="https://www.cdc.gov/flu/avianflu/virus-transmission.htm">bird-flu virus</a> may jump from wild birds to free-range domestic poultry and then to humans who are in contact with poultry. Similar pathways have led to infection by the pathogens that cause <a href="https://doi.org/10.1038/nrmicro.2017.45">Ebola, Zika, HIV, Lyme disease and likely COVID-19</a>.</p>
<p>If a new medical technology increased the risk of a new zoonotic pandemic — however marginally — how would society decide the balance of risk and benefit? If you needed new lungs that were only available in another country, would a health prohibition on the transplant in your own country stop you? </p>
<p>New developments in organ transplant technology may have streamlined a pathway for new zoonotic diseases, but the biotechnology innovators and medical research institutes have not engaged the public on the risks. Failing to do so may jeopardize the potential of a promising therapy.</p>
<h2>Xenotransplantation</h2>
<p>Over 4,400 Canadians are waitlisted for the lifesaving transplant of a new kidney, liver or lung. In 2019, <a href="https://www.blood.ca/en/stories/data-offers-hope-patients-waiting-organ-transplant">250 died waiting</a>. In the United States and elsewhere, <a href="https://www.organdonor.gov/learn/organ-donation-statistics">the supply gap is more extreme</a> and high hopes ride on xenotransplantation: the transplanting of cells, tissues or organs from animals. </p>
<p>Pre-clinical trials of organ transplants from pigs have addressed the technical barriers to xenotransplantation, reducing the likelihood of rejection. Last summer, Maryland School of Medicine surgeons reported the 31-day survival of a baboon after receiving a <a href="https://doi.org/10.1111/ajt.16809">lung from a genetically modified pig</a>. </p>
<p>Weeks later, a team at New York University transplanted a kidney from a genetically modified pig into a <a href="https://doi.org/10.1111/xen.12718">brain-dead person</a>. In December 2021, surgeons at Maryland School of Medicine transplanted a genetically modified pig heart into a <a href="https://doi.org/10.1038/d41586-022-00111-9">living 57-year-old man</a>. </p>
<p>All projects were approved under U.S. Food and Drug Administration (FDA) regulations, and corporate funding was supplemented by the U.S. National Institutes of Health. The next step with the FDA is to approve clinical trials. Normalization of xenotransplantation could happen before there is informed public acceptance of the benefits and risks.</p>
<h2>A potential zoonotic pathway</h2>
<p>As a developmental geneticist, it has been exciting to track these advances. The revolution in designer gene editing (known as CRISPR-Cas9) makes this stunning progress possible. <a href="https://doi.org/10.1126/science.aan4187">CRISPR allows molecules on the surface of pig cells to be modified</a> so the human immune system will not trigger tissue rejection.</p>
<figure class="align-center ">
<img alt="Illustration in blue tones of a human torso with respiratory tract and lungs in red" src="https://images.theconversation.com/files/447231/original/file-20220218-13070-hep7im.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/447231/original/file-20220218-13070-hep7im.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=465&fit=crop&dpr=1 600w, https://images.theconversation.com/files/447231/original/file-20220218-13070-hep7im.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=465&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/447231/original/file-20220218-13070-hep7im.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=465&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/447231/original/file-20220218-13070-hep7im.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=585&fit=crop&dpr=1 754w, https://images.theconversation.com/files/447231/original/file-20220218-13070-hep7im.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=585&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/447231/original/file-20220218-13070-hep7im.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=585&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Zoonotic bacteria and viruses enter most readily through the delicate surfaces of the respiratory tract.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>To prevent human transplant recipients from being infected with pig <a href="https://www.genome.gov/genetics-glossary/Retrovirus">retroviruses</a> (viruses that can integrate their genetic material into the host’s cells), the retroviruses hiding in the pig genome have been <a href="https://doi.org/10.1111/xen.12595">removed by CRISPR editing</a>. The risk of transferring a disease directly from a genetically modified donor pig to the human host is negligible.</p>
<p>However, disease-free transplanted pig organs could become infected after transplantation. Zoonotic bacteria and viruses enter hosts most readily through the <a href="https://doi.org/10.1051/vetres:2006062">delicate surfaces of the respiratory tract</a>, as with COVID-19. Living pig cells in a transplanted lung could readily be infected by an inhaled pig virus, including a novel virus from a wild animal host that has evolved to infect pigs. </p>
<p>After entering the human body, a replicating zoonotic virus could generate millions of mutations a day, because their mechanism for gene copying <a href="https://doi.org/10.3390/v13091882">is naturally error prone</a>. A pig virus replicating in a lung transplanted into a human could <a href="https://theconversation.com/how-do-viruses-mutate-and-jump-species-and-why-are-spillovers-becoming-more-common-134656">produce variants</a> that may be capable of recognizing and infecting human cells. Although likely a rare event, it is not impossible that this could trigger a new zoonotic pandemic.</p>
<h2>Risk, fear and polarization</h2>
<p>The scenario described above could evoke risk and fear from a complex new medical technology. It parallels the thinking involved in <a href="https://doi.org/10.1038/s41591-021-01459-7">vaccine hesitancy</a> or the <a href="https://www.scientificamerican.com/article/why-people-oppose-gmos-even-though-science-says-they-are-safe/">distrust of genetically modified foods</a>. Both are well anchored in today’s political culture. In both cases, citizens increasingly demand prior consent and the choice to opt out — despite possible risks to public health. <a href="https://doi.org/10.1038/s41598-022-05498-z">Vaccine hesitancy</a> has increased the death toll from COVID-19 and delayed economic recovery from the pandemic.</p>
<p>In contrast, distrust of the industrialization of food has discouraged introduction of genetically modified foods that <a href="https://doi.org/10.4161/21645698.2014.967570">enhance nutrition or sustain agricultural productivity</a> in a warming climate. Consumers question whether genetically modified organisms (GMOs) exist for public benefit or for corporate profit.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/447229/original/file-20220218-19-vy6cvf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A protester wearing a winter hat with their face covered with a scarf, hold a paper plate that says 'No GMOs on my plate'" src="https://images.theconversation.com/files/447229/original/file-20220218-19-vy6cvf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/447229/original/file-20220218-19-vy6cvf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=798&fit=crop&dpr=1 600w, https://images.theconversation.com/files/447229/original/file-20220218-19-vy6cvf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=798&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/447229/original/file-20220218-19-vy6cvf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=798&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/447229/original/file-20220218-19-vy6cvf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1003&fit=crop&dpr=1 754w, https://images.theconversation.com/files/447229/original/file-20220218-19-vy6cvf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1003&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/447229/original/file-20220218-19-vy6cvf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1003&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Distrust of the industrialization of food has discouraged introduction of GMO foods.</span>
<span class="attribution"><span class="source">(CP PHOTO/Paul Chiasson)</span></span>
</figcaption>
</figure>
<p>Increasingly, health issues such as <a href="https://theconversation.com/politicizing-covid-19-vaccination-efforts-has-fuelled-vaccine-hesitancy-175416">vaccination</a>, vaping or genetic testing generate highly polarized <a href="https://doi.org/10.1093/ntr/ntaa276">platforms for misinformation</a>, debate and political leverage. <a href="https://thedecisionlab.com/insights/society/social-media-and-moral-outrage/">Social media algorithms amplify extreme positions and elicit strong emotional reactions</a> at the <a href="http://dx.doi.org/10.1177/1461444818822813">expense of the middle ground</a>. When communications from the scientific community are reactive, poorly targeted or <a href="https://doi.org/10.1080/02691728.2020.1739778">unintelligible to the average person</a>, the influence of science in the policy process is diminished.</p>
<p>In 2022, progress in xenotransplant technology makes <a href="https://edition.cnn.com/2022/01/15/opinions/pig-heart-transplant-big-deal-reiner/index.html">good news stories</a>. Immense pressure to resolve the growing organ shortage for transplantation may tempt the biotechnology business and public regulators to be insufficiently critical as they seek permission to proceed with clinical studies. They must prepare for the nature and scale of backlash from those tired of experts and mistrustful of corporate motivation and institutional authority. </p>
<p>Concern about zoonosis from transplants was <a href="https://www.nuffieldbioethics.org/publications/xenotransplantation">voiced over twenty years ago</a>, long before CRISPR transformed the field. <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents/phs-guideline-infectious-disease-issues-xenotransplantation">Since then</a>, there appear to be no hard facts or even a call for research on zoonotic infection through xenotransplants after transplantation. Bioethicists are <a href="https://www.thehastingscenter.org/xenotransplantation-three-areas-of-concern/">flagging the issue now</a>, but the silence about xenotransplant zoonosis from biotechnology corporations and their affiliated preclinical research institutes leaves an open door to a narrative motivated by skepticism and distrust. It is incumbent on them to lead a public dialogue on managing the risk of novel zoonotic diseases arising from infection after transplantation.</p><img src="https://counter.theconversation.com/content/175290/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>J Roger Jacobs receives funding from the Natural Sciences and Engineering Research Council of Canada.</span></em></p>New developments in organ transplants from animals show promise. However, there has been no public engagement about a potential risk. It may streamline a pathway to humans for new zoonotic diseases.J Roger Jacobs, Professor, Department of Biology, McMaster UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1749912022-01-19T13:37:50Z2022-01-19T13:37:50ZPig heart transplant: was David Bennett the right person to receive groundbreaking surgery?<figure><img src="https://images.theconversation.com/files/441348/original/file-20220118-15-jsfbl0.jpg?ixlib=rb-1.1.0&rect=0%2C9%2C6016%2C3998&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Surgeons at University of Maryland School of medicine showing the modified pig's heart that would be transplanted into David Bennett.</span> <span class="attribution"><span class="source">University of Maryland School of Medicine</span></span></figcaption></figure><p>The recent world-first heart transplant from a genetically modified pig to a human generated both <a href="https://www.dailymail.co.uk/news/article-10399737/Pig-heart-transplant-recipient-stabbed-man-seven-times-1988-leaving-wheelchair-bound.html">headlines and ethical questions</a>.</p>
<p>Many of those questions related to the ethics of xenotransplantation. This is the technical term for organ transplants between species. There has been research into this for more than a century, but recent scientific developments involving genetic modifications of animals to stop the organ being rejected appear to make this much more feasible.</p>
<p><a href="https://www.bbc.co.uk/news/world-59951264">Typical questions</a> about xenotransplantation relate to the risks (for example, of transmitting infection), treatment of the animals, and the ethics of genetic modification of animals for this purpose.</p>
<p>But after the recent heart transplant, there were additional questions that had nothing to do with the donor and were all to do with the recipient of the pig heart.</p>
<p>In that case, the recipient, <a href="https://www.washingtonpost.com/dc-md-va/2022/01/13/pig-heart-transplant-stabbing-david-bennett/">David Bennett</a>, a 57-year-old man from Maryland, had been terminally ill with severe heart failure and had ended up on an artificial heart machine. He was not eligible for a conventional heart transplant – several centres had already declined to put him on their waiting list for a transplant – but he was offered the experimental option of a genetically modified pig heart. </p>
<p>After news of the transplant broke, it emerged that 33 years earlier Bennett had been convicted of stabbing a man (Edward Schumaker) in a bar and had been sentenced to ten years in jail. Schumaker had been left in a wheelchair and died of a stroke 19 years later.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1481706575702237187"}"></div></p>
<p>Schumaker’s older sister has since expressed her wish that the heart had gone to “a deserving recipient”. This has reopened a debate on whether those convicted of serious offences should be eligible for organ transplants.</p>
<h2>Strict criteria</h2>
<p>This is <a href="https://www.sciencedirect.com/science/article/pii/S0022522302733084">not a new ethical question</a>, and similar debates in the past have largely been settled by the courts and the medical establishment.</p>
<p>There is a serious shortfall of organs for transplantation. Because of that, there is a need to have strict criteria for eligibility and a transparent ethical process for deciding how to allocate organs once they become available. Typically, those criteria are based on medical factors that predict both the need of the recipient (what is the chance that they will die soon without a transplant) and the benefit of the organ (how likely is the transplant to work and last). Indeed, it was these sorts of factors that made Bennett ineligible for a conventional heart transplant.</p>
<p>But usually transplantation programmes do not pay any attention to the factor that Schumaker’s sister mentioned. They do not exclude convicted felons, even those who are still imprisoned. Guidance from the <a href="https://optn.transplant.hrsa.gov/professionals/by-topic/ethical-considerations/convicted-criminals-and-transplant-evaluation/">US organ transplantation network UNOS</a> says that “status as a prisoner should not preclude [someone] from consideration for a transplant”.</p>
<p>One reason for this arises from a key ethical principle in medical care – that treatment should be allocated equitably. Doctors are not qualified to distinguish “<a href="https://www.washingtonpost.com/dc-md-va/2022/01/13/pig-heart-transplant-stabbing-david-bennett/">sinners from saints</a>”, nor do we think they should be deciding which patients are more deserving.</p>
<p>Decisions about how best to punish someone convicted of a crime are assessed in a totally different domain – the courts, where of course there are careful rules and procedures for assessing whether a person is guilty of a particular offence and what the consequence should be. It would be possible for a country to decide that as a punishment for a particularly severe offence, someone should not be eligible for certain scarce or expensive publicly funded medical treatments. In <a href="https://cdn.penalreform.org/wp-content/uploads/2019/05/PRI-Global-prison-trends-report-2019_WEB.pdf">a number of countries</a>, prison healthcare is underfunded and limited – for example, in the <a href="https://academic.oup.com/jpubhealth/article/43/2/e342/6158062?login=true">Philippines</a>. However, <a href="https://www.unodc.org/documents/justice-and-prison-reform/Nelson_Mandela_Rules-E-ebook.pdf">UN rules on the treatment of prisoners</a> – the so-called Nelson Mandela Rules – state that prisoners should have access to the same standards of healthcare as are available in the community.<br>
In the US, an influential <a href="https://supreme.justia.com/cases/federal/us/429/97/">1976 supreme court decision</a> held that it would be “cruel and unusual punishment” to withhold medical treatment from prisoners. In the UK, prisoners have full access to NHS medical treatment.</p>
<p>Even if there were reduced priority for treatment for prisoners, a separate reason might be thought to apply in Bennett’s case. Since he had served his sentence many years previously, it would be unfair to continue to discriminate against him for medical treatment. Although it is understandable if a victim’s family feel differently, most of us think that people who have completed their sentence should be treated fairly and given an opportunity to return to a normal life.</p>
<p>In fact, the nature of this new development in transplantation might, in one way, diminish such ethical concerns. One key reason why difficult questions about organ allocation arise is because there is a shortage of organs – <a href="https://www.nhsbt.nhs.uk/what-we-do/transplantation-services/organ-donation-and-transplantation/">470 people died in the UK last year</a> waiting for a transplant. If xenotransplantation does become a realistic option, it may avoid the difficult problem of having to pick and choose between patients with organ failure.</p><img src="https://counter.theconversation.com/content/174991/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Dominic Wilkinson receives funding from the Wellcome Trust. </span></em></p>Heart-recipient David Bennett had done jail time for stabbing a man.Dominic Wilkinson, Consultant Neonatologist and Professor of Ethics, University of OxfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/848642017-11-30T10:08:55Z2017-11-30T10:08:55ZChimps, racism and the definition of death: the heart transplant story<figure><img src="https://images.theconversation.com/files/196741/original/file-20171128-28856-5zra8q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Dmitry Kalinovsky/Shutterstock.com</span></span></figcaption></figure><p>In the summer of 1967, three of the four cardiac surgeons competing to perform the first human heart transplant were simultaneously <a href="https://books.google.co.uk/books/about/Every_Second_Counts.html?id=2Fv9dRT9TC4C&redir_esc=y">just hours from their place</a> in the history books. But each was thwarted – none of the planned operations went ahead. All four would come close again. But the race was finally only settled on December 3, 1967. Like that other iconic moment of the late 1960s, man’s small step onto the moon, the first human heart transplant was a giant leap that would be felt around the world.</p>
<p>The South African doctor <a href="https://theconversation.com/how-an-historic-heart-transplant-created-a-celebrity-scientist-50-years-ago-88277">Christiaan Barnard</a> was spoken of in the same breath as Neil Armstrong after he abruptly became a worldwide celebrity on December 3, 1967. His patient, 55-year-old Louis Washkansky, was also catapulted into the spotlight for the 18 tumultuous days he lived after receiving a new heart in Cape Town from 25-year-old traffic accident victim Denise Darvall. </p>
<p>A gifted surgeon and trailblazer from a resource poor country, Barnard was nevertheless a peripheral character in the field of cardiac transplantation research. Years of meticulous work and animal experimentation by Americans Norm Shumway, Richard Lower and Adrian Kantrowitz meant that by 1967 the quest to be first was no less exciting than the space race. None of them expected a man with no background in cardiac transplantation research to leapfrog them, but Barnard’s imperious self-confidence would surprise everyone.</p>
<h2>Primate hearts</h2>
<p>There had been a false start in 1964 when American surgeon James Hardy turned to desperate measures in an attempt to save a patient’s life. He was aware that a man had recently been kept alive with a circus chimp’s kidney. As a result, Hardy had purchased four chimps and decided to transplant one of their hearts into his patient. It was a disaster. The man died on the table and the public backlash was fierce. Hardy never attempted another heart transplant.</p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/196954/original/file-20171129-29098-1nchbg9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/196954/original/file-20171129-29098-1nchbg9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=800&fit=crop&dpr=1 600w, https://images.theconversation.com/files/196954/original/file-20171129-29098-1nchbg9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=800&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/196954/original/file-20171129-29098-1nchbg9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=800&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/196954/original/file-20171129-29098-1nchbg9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1006&fit=crop&dpr=1 754w, https://images.theconversation.com/files/196954/original/file-20171129-29098-1nchbg9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1006&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/196954/original/file-20171129-29098-1nchbg9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1006&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Christiaan Barnard, 1968.</span>
<span class="attribution"><span class="source">Eric Koch / Anefo</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>Over the next few years, the world eagerly waited for one of the three American doctors vying for success to write their name into history. But history had other ideas, as Barnard, who had learnt much while observing Shumway and Lower, beat Kantrowitz by a matter of days. </p>
<p>But as mentioned, his patient, Louis Washkansky, died of a chest infection 18 days later. Barnard, perhaps ill-advisedly, revealed his quintessentially surgical mindset when he announced that despite the patient’s death, his operation had been a success, as the postmortem revealed a “beautiful heart”.</p>
<p>This was a pattern that would repeat itself across the world as heart transplantation took off like wildfire. But suturing in a heart was the easy bit; it would be two decades until we understood and could effectively treat rejection.</p>
<p>After initial excitement, the realisation that most patients lived weeks or months meant practically everyone abandoned it. In 1968, there were 100 heart transplants performed worldwide; in 1970, <a href="https://books.google.co.uk/books/about/Every_Second_Counts.html?id=2Fv9dRT9TC4C&redir_esc=y">just 18</a>. Norm Shumway almost <a href="https://books.google.co.uk/books?id=QOXxDAAAQBAJ&printsec=frontcover&dq=matters+of+the+heart+thomas+morris&hl=en&sa=X&ved=0ahUKEwiRnJqw8c3XAhWMthoKHYUPABcQ6AEIKDAA#v=onepage&q=matters%20of%20the%20heart%20thomas%20morris&f=false">single-handedly</a> kept the idea alive and hence is remembered as the father of heart transplantation, even if it was Barnard lauded on the front cover of TIME Magazine, or partying with Sophia Loren on the inside pages.</p>
<h2>Ethical dilemmas</h2>
<p>The jubilant atmosphere surrounding Washkansky’s transplant happened against the backdrop of apartheid South Africa. A country shunned by much of the world rejoiced at their opportunity to show they were a modern nation. But the spectre of race had clouded the ethical issues surrounding transplant in both South Africa and 1960s America.</p>
<p>Barnard’s hospital had secretly decided to avoid a transplant operation involving a black recipient, lest they be accused of experimenting on a subjugated minority. One month prior to his transplant, Washkansky, a white immigrant from Lithuania, was moments from receiving the heart of a black man, but ultimately a medical reason gave the hospital a welcome excuse to cancel the procedure. Denise Darvall was also white and so while the gift of her heart was celebrated around the world, her kidneys were more controversial as they were donated to a mixed race 10-year-old boy.</p>
<p>The other major ethical and theological topic of discussion concerned how to appropriately retrieve organs from a donor. Patients with a fatal head injury may have irreparable brain damage but their heart will continue to beat, a concept known as <a href="https://www.livescience.com/42301-brain-death-body-alive.html">brain death</a>. This represents the best chance for successful transplantation as organs stay viable as long as the heart is beating. Once the heart stops beating and circulatory death occurs, organs begin to get damaged, especially the heart itself.</p>
<p>Brain death was not legally recognised in 1967 – death was then defined by American law as the lack of a heartbeat. Shumway was critical of this archaic “boy Scout definition” of death. It meant doctors would have to wait for the donor’s heart to spontaneously stop beating. South Africa’s looser legal definition of death benefited Barnard, who simply needed the approval of the state’s forensic pathologist, in contrast to staunch initial opposition to recognising brain death in the US. </p>
<p>The perils of operating in this new frontier were made all too apparent when Japanese surgeon <a href="http://content.time.com/time/world/article/0,8599,2054268,00.html">Juro Wada</a> performed his country’s first heart transplant. His donor was what today would be recognised as brain dead but Wada was charged with murder and waited several years to be exonerated. Japan didn’t perform another heart transplant until 1999. </p>
<h2>Heart legacies</h2>
<p>And what about the legacy of xenotransplantation – organ donation across species? This had kept a low profile since the catastrophic 1964 attempt to transplant a chimp’s heart. But in 1984, the American surgeon Leonard Bailey controversially selected a baboon’s heart in an attempt to save a two-week-old girl who became known as <a href="https://news.llu.edu/clinical/stephanie-s-heart-story-of-baby-fae">Baby Fae</a>. She lived for three weeks. Allegations later surfaced that Bailey <a href="https://en.wikipedia.org/wiki/Baby_Fae#Ethics">rejected</a> an available human donor and exaggerated chances of success on the consent form.</p>
<p>The heart transplant was the 20th century’s landmark medical event. In the UK, there are six heart transplant centres, the largest of which is Papworth Hospital in Cambridge, where I received my training. The first recipient of a successful heart transplant in the UK had their operation at Papworth. Another Papworth patient is approaching the 35th anniversary of their transplant, thought to be one of the longest surviving heart transplant patients in the world. Papworth has recently <a href="http://www.dcdheart.com/what-is-dcd/heart-transplantation/">pioneered</a> a new way to perform transplants, so that donors who have suffered circulatory death are now <a href="http://www.bbc.co.uk/news/health-32056350">also suitable</a>. This means the number of potential donors will soon <a href="http://www.independent.co.uk/news/health/heart-transplant-operation-new-waiting-list-halved-a7924896.html">increase considerably</a>. </p>
<p>Tens of thousands of lives have been saved since Denise Darvall’s posthumous act of generosity and heart transplantation has grown to comprise about <a href="http://www.who.int/transplantation/gkt/statistics/en/">5,000 operations</a> around the world each year. Yet in 2016, <a href="https://www.theguardian.com/society/2017/sep/04/silence-transplants-deadly-organs-shortage-nhs">457 people</a> died awaiting organ transplant in the UK. The operation itself has only been modified slightly since 1967 and despite our best attempts to build a replacement heart, the gift of organ donation remains many people’s best hope for life.</p><img src="https://counter.theconversation.com/content/84864/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Rohin Francis 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>Human heart transplantation is 50 years old.Rohin Francis, Cardiologist and Clinical Research Fellow, UCLLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/606482016-06-07T13:28:26Z2016-06-07T13:28:26ZHuman-pig ‘chimeras’ may provide vital transplant organs, but they raise ethical dilemmas<figure><img src="https://images.theconversation.com/files/125519/original/image-20160607-15049-l3kfbe.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Growing human organs in pigs mean they're doing our dirty work for us.</span> </figcaption></figure><p>Organ transplantation is one of modern medicine’s success stories, but it is hampered by a scarcity of donor organs. Figures for the UK published by the <a href="http://www.odt.nhs.uk/uk-transplant-registry/annual-activity-report/">NHS Blood and Transport Service</a> show that 429 patients died in 2014-2015 while awaiting an organ. What’s more, many of the 807 removed from the waiting list will have been removed because they became too ill to receive an organ, and are likely to have died as a result.</p>
<p>So while there is a strong ethical imperative to increase the supply of donor organs, many of the methods tried or proposed – <a href="https://theconversation.com/organ-donation-does-presumed-consent-work-49478">presumed consent</a>, allowing <a href="https://theconversation.com/black-market-lottery-organ-donation-and-the-international-transplant-trade-23980">organs to be bought and sold</a>, and using lower-grade organs such as those from donors with HIV – are themselves controversial. And even if we accept these approaches it’s unlikely they will be sufficient to meet the demand.</p>
<p><a href="https://theconversation.com/genome-editing-poses-ethical-problems-that-we-cannot-ignore-39466">Gene editing</a> techniques such as <a href="https://www.addgene.org/CRISPR/guide/">CRISPR</a> could provide the answer. These techniques allow us to make precise changes in the DNA of living organisms with exciting prospects for treating disease – for example by modifying human DNA to remove genes that cause disease or insert genes associated with natural immunity to conditions such as HIV/AIDS. However, gene editing the DNA of animals could prove equally important for the medical treatment of humans.</p>
<p>Scientists are now working on a technique that would allow <a href="http://www.bbc.co.uk/news/health-36437428">human organs to be grown inside pigs</a>. The DNA within a pig embryo that enables it to grow a pancreas is deleted, and human stem cells are injected into the embryo. These stem cells have the ability to develop into any type of cell within the body, and <a href="http://dx.doi.org/10.1016/j.cell.2010.07.039">previous experiments</a> using rats and mice suggest that they will automatically fill the gap created by the missing pancreas genes and form a pancreas that consists of predominantly genetically human cells.</p>
<p>The idea of transplanting organs from pigs into humans is not new. Transplants between different species, or <a href="http://nuffieldbioethics.org/project/xenotransplantation/">xenotransplantation</a>, was considered promising in the 1990s but fell from favour due to the challenges of preventing the human immune system from rejecting pig organs, and concerns about possible transmission of infectious diseases from pigs to humans. Modern gene editing techniques may help alleviate both concerns: rejection is less likely since the organ will be more closely resemble a human one, while other scientists have demonstrated that CRISPR can also be used to delete retroviruses from the pig genome.</p>
<p>However, some will undoubtedly protest that the risks are still too high. Often these objections appeal to the so-called precautionary principle, which states that action should be taken to avert risks even if their existence and magnitude is uncertain. Attractive though this idea is, the <a href="http://www.tandfonline.com/doi/abs/10.1080/03605310600912642">precautionary principle</a> is only defensible if it is evidence based, and balances the risks of innovation against the known harms of not using the technology.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/125518/original/image-20160607-15038-13vyjxu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/125518/original/image-20160607-15038-13vyjxu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/125518/original/image-20160607-15038-13vyjxu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=415&fit=crop&dpr=1 600w, https://images.theconversation.com/files/125518/original/image-20160607-15038-13vyjxu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=415&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/125518/original/image-20160607-15038-13vyjxu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=415&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/125518/original/image-20160607-15038-13vyjxu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=522&fit=crop&dpr=1 754w, https://images.theconversation.com/files/125518/original/image-20160607-15038-13vyjxu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=522&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/125518/original/image-20160607-15038-13vyjxu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=522&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This 4th century BC stature depicts the Chimera of Arezzo as a fire-breathing hybrid of lion, goat and snake.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/carolemage/22636282885">carolemage</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<h2>Practical medicine meets practical ethics</h2>
<p><a href="http://www.ncregister.com/site/article/whats-wrong-with-human-animal-chimeras/">Others</a> will argue that it is inherently wrong to create human-animal hybrids, so-called <a href="http://www.britannica.com/topic/chimera-genetics">chimeras</a>; that it is contrary to human dignity, or constitutes “playing God”. It’s hard to understand the rationale for such claims given that humans’ biological nature is neither fixed nor categorically separated from that of other organisms. Even without technological interventions we share much of our DNA with other species, host millions of non-human cells within our bodies, and may have absorbed some of their DNA by <a href="http://www.the-scientist.com/?articles.view/articleNo/42420/title/Horizontal-Gene-Transfer-a-Hallmark-of-Animal-Genomes-/">horizontal transfer</a>.</p>
<p>Even if creating human-animal chimeras is not intrinsically wrong, is there an ethical problem in experimenting on and harvesting organs from a creature that is part-human? It has been suggested that human stem cells might become incorporated into the pig’s brain, making the pig “more human”. But even if stem cells enhanced the pig’s brain function (as some <a href="http://www.cnet.com/news/mice-implanted-with-human-brain-cells-become-smarter/">experiments have suggested</a>), it seems implausible that the pig would acquire anything like the cognitive sophistication that would put it morally on a par with humans.</p>
<p>We might question whether the use of pigs as a source of organs for humans is permissible, even leaving aside any suggestion that their moral status is somehow enhanced by the presence of human cells. Jeremy Bentham, the father of utilitarianism, <a href="http://www.econlib.org/library/Bentham/bnthPML18.html">famously wrote</a>: “The question is not, Can they reason? nor, Can they talk? but, Can they suffer?”. </p>
<p>If this is the case pigs undoubtedly qualify for moral consideration. It is often argued that since pigs and other livestock animals are routinely sacrificed for our culinary pleasure (meat being neither necessary for a healthy diet nor an environmentally efficient way of producing protein), it would be odd to prohibit their use in life-saving medical research and treatment. But meat-eating itself is under increased ethical scrutiny today which, even while it is unlikely to be banned anytime soon, makes for a weak foundation on which to justify extending animal exploitation to a new arena. </p>
<p>Other approaches such as <a href="https://www.theguardian.com/science/2015/jul/08/laboratory-grown-organs-transform-lives">laboratory-grown organs</a>, or organs grown in “zombie” animals genetically engineered to lack sentience, could in the future offer the benefits of the chimera technique without the animal welfare problems. Until then, we shouldn’t try to duck difficult judgements about weighing up human and animal welfare. If the risks can be sufficiently controlled, then it’s hard to envisage society choosing to forego the life-saving opportunities of this technology. But we must also recognise that the choices we face now are influenced by earlier decisions about research priorities, and that these too require careful ethical consideration.</p><img src="https://counter.theconversation.com/content/60648/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jonathan Hughes does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>We’re living longer and more ill lives – could we use animals to grow human organs for transplants?Jonathan Hughes, Senior Lecturer in Ethics, Keele UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/577012016-04-14T13:26:24Z2016-04-14T13:26:24ZHow long before we can transplant an animal’s heart in a human?<figure><img src="https://images.theconversation.com/files/118579/original/image-20160413-22081-20dy3i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A ready source of hearts...one day.</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/cat.mhtml?lang=en&language=en&ref_site=photo&search_source=search_form&version=llv1&anyorall=all&safesearch=1&use_local_boost=1&autocomplete_id=&search_tracking_id=mSbrvoIupQlaQly9s3K79Q&searchterm=pigs&show_color_wheel=1&orient=&commercial_ok=&media_type=images&search_cat=&searchtermx=&photographer_name=&people_gender=&people_age=&people_ethnicity=&people_number=&color=&page=1&inline=272113169">www.shutterstock.com</a></span></figcaption></figure><p><a href="http://www.nature.com/ncomms/2016/160405/ncomms11138/full/ncomms11138.html">The announcement</a> that researchers in the US kept a genetically engineered pig’s heart beating in a baboon for nearly three years has, in some quarters, revived speculation about the prospect of pig organs being suitable for transplantation into humans. </p>
<p>Research into xenotransplantation (the transplant of live organs, tissues or cells from animals to humans) dates from at least the 1900s, when research on it and allotransplants (human-to-human transplants) <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1406409/">ran in parallel</a>. </p>
<p>Interest in animal-to-human transplants was renewed in the 1980s when the development of immunosuppressant drugs, such as cyclosporine, <a href="http://www.nejm.org/doi/full/10.1056/NEJM198310063091401">made transplants between humans more effective</a>. The hope was that such drugs –- which lower the body’s ability to reject a transplanted organ – could be used in cross-species transplants. Also, advances in genetic engineering and cloning in the 1990s and 2000s resulted in <a href="http://www.ncbi.nlm.nih.gov/pubmed/12493821">genetically engineered pigs</a> without the antibody that leads to their organs being immediately rejected by humans. These two advances led some to believe that cross-species transplants were an imminent possibility. </p>
<p>While some may see this latest research from the US as moving us a step closer to xenotransplants, a closer inspection of the study indicates that it is premature to view such a prospect as imminent. There are several reasons why this research is more of an inch than a significant step forward. </p>
<h2>Significant hurdles</h2>
<p>In this study, genetically engineered pigs’ hearts were transplanted into five baboons and while one of the hearts remained healthy for nearly three years, one baboon died from an antibiotic-resistant infection about five months after the transplant. The median (middle) survival rate was 298 days. While a survival time of nearly three years might seem reasonable given the shortage of human organs available for transplant, it is important to note that these were not life-supporting transplants – the baboons’ hearts remained in their chests with the pig hearts attached to the baboons’ abdomens. So the pig hearts were not functioning as the baboons’ hearts. And only one heart survived in a baboon’s abdomen for nearly three years.</p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/118575/original/image-20160413-22040-qpsyn3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/118575/original/image-20160413-22040-qpsyn3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=769&fit=crop&dpr=1 600w, https://images.theconversation.com/files/118575/original/image-20160413-22040-qpsyn3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=769&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/118575/original/image-20160413-22040-qpsyn3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=769&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/118575/original/image-20160413-22040-qpsyn3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=967&fit=crop&dpr=1 754w, https://images.theconversation.com/files/118575/original/image-20160413-22040-qpsyn3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=967&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/118575/original/image-20160413-22040-qpsyn3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=967&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A pig’s heart.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/cat.mhtml?lang=en&language=en&ref_site=photo&search_source=search_form&version=llv1&anyorall=all&safesearch=1&use_local_boost=1&autocomplete_id=&searchterm=pig%27s%20heart&show_color_wheel=1&orient=&commercial_ok=&media_type=images&search_cat=&searchtermx=&photographer_name=&people_gender=&people_age=&people_ethnicity=&people_number=&color=&page=1&inline=268838735">www.shutterstock.com</a></span>
</figcaption>
</figure>
<p>The baboons were initially given large doses of immunosuppressant drugs so that their bodies would not reject the pig hearts. These drugs are needed because even though pigs can now be genetically engineered to minimise the risk of hyperacute rejection – where the organ is rejected within minutes of being transplanted – the baboons’ immune systems still need to be suppressed to prevent their bodies perceiving the hearts as foreign. </p>
<p>The large doses would not be tolerated by humans in the long term and so the researchers reduced the level of the immunosuppressants to see if the pigs’ hearts would still function. When they did this, two of the baboons almost immediately began to reject their hearts and the anti-pig antibody in them was reactivated. While the pig hearts connected to two of the baboons continued to function with the lower dose of drugs, once the immunosuppressants were discontinued altogether the hearts were rejected (at 616 and 945 days). </p>
<p>These are important findings because if such an immunosuppressant regime was replicated in a pig-to-human transplant, it seems that the recipient’s immune system would need to be suppressed on a long-term, if not lifelong, basis – otherwise the anti-pig antibody could well return. Whether people would tolerate taking these drugs for a lifetime is a different matter and research on this is still needed.</p>
<p>While the study may provide further evidence that there are ways of managing one of the types of rejection that is predicted to follow from a xenotransplant, there are other types which have yet to be addressed. These have not been studied in detail because they do not come into play until instant hyperacute rejection has been addressed. So, we do not know how these other forms of rejection will operate, if at all, nor have we really begun to consider appropriate strategies to counter them.</p>
<p>As these were not life-supporting transplants, we still do not know whether – and this study is clearly not evidence that – a pig’s heart could function and support the life of a baboon, let alone a human. The question whether the heart of a quadruped can appropriately function in a biped remains unanswered.</p>
<p>While strategies to meet the shortfall in organs available for use in transplantation shouldn’t be too readily dismissed, given the huge human cost involved, it would be rash to suggest that we are now significantly closer to using genetically engineered pigs as sources of organs for humans.</p><img src="https://counter.theconversation.com/content/57701/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sara Fovargue 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 baboon survived nearly three years with a pigs heart, so does that mean cross-species transplantation is imminent?Sara Fovargue, Reader in Law, Lancaster UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/514892015-12-03T18:52:53Z2015-12-03T18:52:53ZGene editing could open up animal organ transplants into humans<figure><img src="https://images.theconversation.com/files/103988/original/image-20151202-14432-1nthixl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The cultivation of pig organs for human transplantation carries great risk and promise.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/cafnr/14205076730/in/photolist-nDfJq3-77pp74-HMLwA-8vyGek-6jajSA-9cV7vn-w89uxS-wp4YS5-aFckNP-wqernV-wqefbX-w89FsN-6K7Wbk-5ja3od-6KFLvQ-w89GBy-wp5PBu-5UANa9-5fC17g-oeL9wM-nVBSHj-nDfmGx-nDfmwn-77aYyR-h3VdS2-bKVUtR-wpL5Ge-wpKos6-6TAgjG-drdR6K-adykrD-aFfqjY-p84WyW-aFgcNw-bsWSt-xw5rVs-dre18N-fvfie6-fvuzp1-p84oSb-aFg89w-oeKZfS-cyKeqy-oKie3d-6A6uEJ-nDfvcC-3wCZdT-wiSmqB-7rwmuE-5dF49U">CAFNR/flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span></figcaption></figure><p>The clinical potential and ethical difficulty posed by gene-editing technology, which can “find and replace” targeted genes, is <a href="http://www.sciencemag.org/content/346/6213/1258096?intcmp=collection-crispr">seemingly endless</a>. </p>
<p>But while public attention is focused on whether we should use it to change the genes of embryos, application of the technology to genetically modify pig tissues and organs for transplantation into humans could potentially have a bigger and more immediate impact on human health.</p>
<p>The transplantation of living cells, tissues, or organs from one species to another is known as <a href="http://www.ncbi.nlm.nih.gov/pubmed/22019026">xenotransplantation</a>. It has long been championed as a solution to the shortage of human donor organs. Xenotransplantation could be used either as definitive therapy or to “buy time” while the patient waits for a human donor organ. </p>
<p>While progress has been slow, <a href="http://www.ncbi.nlm.nih.gov/pubmed/25386833">trials</a> have demonstrated benefit in patients with type 1 diabetes who are transplanted with porcine pancreatic cells. And <a href="http://www.sciencemag.org/content/350/6264/1101.abstract">gene-editing research published in October</a> shows incredible promise for making xenotransplantation a reality.</p>
<h2>The challenges of xenotransplantation</h2>
<p>Xenotransplantation faces two major challenges: the risk of immune rejection and the risk of transmitting diseases from animals to humans (xenozoonosis). </p>
<p>Immune rejection of transplants among humans can be mitigated by carefully matching donor and recipient. But it’s all much more difficult in the case of humans and pigs. The genetic divide means the human immune system is primed to recognise the pig graft as foreign and to attack it. </p>
<p>In terms of xenozoonosis, of particular concern are porcine <a href="https://en.wikipedia.org/wiki/Endogenous_retrovirus">endogenous retroviruses</a>. These are found in the pig genome and cannot be eliminated by bio-secure breeding. If these retroviruses become activated, they can cause serious infection in human hosts. </p>
<p>While no cases of such infections have been recorded in human recipients of porcine grafts, these viruses have been shown to <a href="http://www.nature.com/nm/journal/v3/n3/abs/nm0397-282.html">infect human cells in vitro</a>.</p>
<p>Scientists have explored a <a href="http://www.ncbi.nlm.nih.gov/pubmed/19566656">range of strategies</a> – either reducing or suppressing the expression of porcine endogenous retroviruses in pig tissue – <a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0122059">to mitigate the risk</a> of transmission to humans. But these have limited efficiency and are costly. </p>
<p>“Find and replace” gene editing (CRISPR/Cas9), in contrast, appears to provide real promise. </p>
<p><a href="http://www.sciencemag.org/content/350/6264/1101.abstract">Scientists from Harvard University</a> have used the technology to target and inactivate porcine endogenous retroviruses in the genome of pig kidney cells. They showed more than a 1,000-fold reduction of viral transmission to human cells in vitro. </p>
<p>The researchers managed to target genes that sit on the surface of porcine cells, which are known to trigger a human immune response. Their work shows genuine possibility for porcine tissues and organs being modified and transplanted into humans without the need for immunosuppressant medication and with little risk of porcine endogenous retrovirus transmission.</p>
<h2>Scientific challenges and ethical concerns</h2>
<p>But the gene-editing technology the Harvard scientists used is not without problems. A number of <a href="https://theconversation.com/gene-editing-in-embryos-is-fraught-with-scientific-and-ethical-issues-51476">scientific challenges and ethical concerns</a> remain. </p>
<p>Foremost is the uncertain safety profile of CRISPR/Cas9 gene editing. While the scientists found the technology didn’t cause any unintended mutations in the porcine genome, its use in non-viable human embryos <a href="http://link.springer.com/article/10.1007%2Fs13238-015-0153-5">has been reported</a> to split DNA segments at sites that weren’t targeted. This raises the possibility it <a href="http://genome.cshlp.org/content/early/2013/11/12/gr.162339.113">may cause mutations that could lead to cancer</a>.</p>
<p>One of the great challenges of xenotransplantation is that pathogens occurring in the organ may be unknown. While the risk of xenozoonoses due to unknown pathogens is low, the potential risks are profound. And we should avoid scientific hubris in our enthusiasm for exploring the implications of this technology for xenotransplantation.</p>
<p>The technology also raises biosecurity and regulatory concerns, because in contrast with traditional gene modification techniques it’s efficient, cheap and simple to apply. As bioscience becomes “democratised”, technologies like CRISPR/Cas9 may be used by individuals or groups outside regulated research environments or with intent to synthesise virulent organisms to inflict harm on others.</p>
<p>The application of CRISPR/Cas9 in transplantation may also increase pressure for it to be used widely, in settings that are currently tightly restricted or controlled. </p>
<p>And the possibility that it could be used to change sperm, egg and embryonic cells, which are known as germline cells, raises the spectre of eugenics and human enhancement for non-medical reasons. This could also lead to trans-generational risks. </p>
<p>While CRISPR/Cas9 may provide the impetus for progress in xenotransplantation that’s been lacking for almost two decades, only if it proceeds in an ethically defensible manner, and with robust regulatory oversight, will it gain widespread public acceptance.</p><img src="https://counter.theconversation.com/content/51489/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Public attention is focused on whether we should use gene editing technology on embryos, but it could potentially have a bigger and more immediate impact on human health via animal organ donation.Ronald Kam Fai Fung, Research Scholar, Centre for Values, Ethics and the Law in Medicine, University of SydneyIan Kerridge, Associate Professor in Bioethics & Director, Centre for Values and Ethics and the Law in Medicine, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/42912011-12-13T19:43:38Z2011-12-13T19:43:38ZXenotransplantation: using pigs as organ and tissue donors for humans<figure><img src="https://images.theconversation.com/files/6337/original/tchnchvm-1323737775.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Pigs may be the answer to Australia's organ donor shortage.</span> <span class="attribution"><span class="source">Thornypup</span></span></figcaption></figure><p>Transplantation is the best available treatment for many serious health problems including diabetes, kidney failure and heart disease. These conditions affect millions of people worldwide and the cost of treatment, loss of productivity and reduced quality of life are enormously expensive to society. </p>
<p>Although transplantation offers a lifeline to these patients, there is far greater demand for organs and tissues than can ever be met using human donors. Even with the <a href="http://www.donatelife.gov.au/">government-driven push</a> to increase the donation rate in Australia, many patients will become too sick to receive a transplant or will die while on the waiting list. </p>
<p>Some scientists believe that <a href="https://theconversation.com/its-a-vision-thing-the-case-for-a-far-sighted-approach-to-stem-cell-research-1790">stem cells will ultimately provide a solution</a> to this pressing medical problem, but growing a highly complex organ from stem cells remains in the realms of science fiction, at least for now. </p>
<p>A treatment that is much closer to reality, and indeed has already entered early clinical trials, is the transplantation of animal organs, tissues or cells into humans. This is called xenotransplantation.</p>
<h2>Which species?</h2>
<p>Humans are primates, so the obvious choice of donor animal for xenotransplantation would appear to be another member of the primate family (chimpanzees and baboons, for instance) because of their physiological similarity. But non-human primates have been ruled out as donors for several compelling practical and ethical reasons. </p>
<p>One of the risks to transplant recipients is infection by viruses transmitted by the transplanted organ. As our closest cousins in the animal kingdom, primates are more likely than other animals to carry viruses capable of infecting humans; HIV, the virus responsible for AIDS, originated in chimpanzees. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/6341/original/zwtq9dgn-1323738604.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/6341/original/zwtq9dgn-1323738604.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/6341/original/zwtq9dgn-1323738604.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/6341/original/zwtq9dgn-1323738604.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/6341/original/zwtq9dgn-1323738604.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/6341/original/zwtq9dgn-1323738604.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/6341/original/zwtq9dgn-1323738604.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Primates aren’t the best fit to donate organs and tissues to humans.</span>
<span class="attribution"><span class="source">Troy B Thompson</span></span>
</figcaption>
</figure>
<p>This “relatedness” also poses ethical problems, with the public understandably reluctant to exploit animals that share many features with humans. And even if you discount the ethical question, it’s hard to imagine being able to breed enough primates to meet the increasing demand for donor organs.</p>
<p>Pigs, on the other hand, tick many of the boxes. They can be raised in a clean environment, so the risk of infection from pig donors may actually be lower than that from human donors. They are already widely bred for the food industry, solving the supply issue and, provided they are treated humanely, present less of an ethical dilemma. </p>
<p>Material from pigs has been routinely and safely used for medical purposes for decades, with <a href="http://www.theaustralian.com.au/news/nation/rudds-second-heart-valve-replacement-riskier/story-e6frg6nf-1226098607967">heart valves</a> the best known example. The evidence from animal models suggests that most pig organs will work properly in human recipients.</p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/6338/original/rw9m3cdb-1323738102.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/6338/original/rw9m3cdb-1323738102.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/6338/original/rw9m3cdb-1323738102.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/6338/original/rw9m3cdb-1323738102.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/6338/original/rw9m3cdb-1323738102.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/6338/original/rw9m3cdb-1323738102.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/6338/original/rw9m3cdb-1323738102.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">There are still some major barriers to overcome before xenotransplantation becomes a clinical possibility.</span>
<span class="attribution"><span class="source">Ro Irving</span></span>
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</figure>
<p>On the downside, the evolutionary distance between pigs and humans means that the human immune system mounts a very strong response to pig organs. The drugs that are used to prevent rejection of human transplants are simply not powerful enough when it comes to pig transplants. </p>
<p>One solution for this problem is to genetically modify pigs so that their organs will not be recognised as foreign when transplanted into humans. <a href="http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61091-X/abstract">Several groups</a> around the world, including in Australia, have produced GM pigs for xenotransplantation research. These pigs are still in the testing phase, but the progress that has been made over the last 10 years suggests that the move to the clinic is not too far away. </p>
<h2>Treating diabetes with pig islets</h2>
<p>Pigs may also be the key to future treatment of diabetes. Insulin, the hormone that controls the level of sugar in the blood, is made by clusters of cells in the pancreas called islets. People with type 1 diabetes have abnormally high blood sugar because their islets are destroyed by the immune system. While regular insulin injections restore some control, the long term prospects are poor, with complications including renal failure and blindness. </p>
<p>Transplantation with human islets is an option open to only a handful of patients. Pig islets are an attractive alternative, because pig insulin is 98% identical to human insulin and was used to treat patients before recombinant human insulin became available.</p>
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<img alt="" src="https://images.theconversation.com/files/6339/original/txhy9bkg-1323738187.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/6339/original/txhy9bkg-1323738187.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/6339/original/txhy9bkg-1323738187.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/6339/original/txhy9bkg-1323738187.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/6339/original/txhy9bkg-1323738187.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/6339/original/txhy9bkg-1323738187.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/6339/original/txhy9bkg-1323738187.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Pig insulin was used for decades to treat people with diabetes.</span>
<span class="attribution"><span class="source">Jill A Brown</span></span>
</figcaption>
</figure>
<p>In a clinical trial currently taking place in New Zealand, pig islets contained within microcapsules have been injected into the abdomen of 11 patients with diabetes. The microcapsules allow nutrients to get in and insulin to get out, but importantly they also protect the pig islets from the recipient’s immune system so that no anti-rejection drugs are needed. Early results suggest that the microcapsule treatment will not be a complete cure, but may benefit patients with severe diabetes. </p>
<p>In the meantime, many other strategies are being explored. <a href="http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61091-X/abstract">Results from animal models</a> showing islets from GM pigs can reverse diabetes for many months are particularly encouraging. </p>
<h2>Future xenotransplantation</h2>
<p>A recent <a href="http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61091-X/abstract">review in the prestigious medical journal The Lancet</a> is carefully optimistic that clinical xenotransplantation may soon become a reality, particularly for cellular grafts such as islets. Will this be, as suggested by the authors of the review, the “next medical revolution”? We’ll have to wait and see.</p><img src="https://counter.theconversation.com/content/4291/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Peter Cowan receives funding from the National Health and Medical Research Council of Australia (NHMRC) and the Juvenile Diabetes Research Foundation (JDRF).</span></em></p>Transplantation is the best available treatment for many serious health problems including diabetes, kidney failure and heart disease. These conditions affect millions of people worldwide and the cost…Peter Cowan, Co-director of the Immunology Research Centre, St Vincent's Hospital MelbourneLicensed as Creative Commons – attribution, no derivatives.