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categories: ["bodies", "genetics"]categories: ["bodies", "genetics"]tags: ["transplantation", "organ shortage", "genome editing", "immunology", "pigs", "clinical trials"]tags: ["transplantation", "organ shortage", "genome editing", "immunology", "pigs", "clinical trials"]summary: "The transplantation of organs between species, now pursued with genetically engineered pigs whose antigens and clotting proteins have been altered to survive in a human recipient."summary: "The transplantation of organs between species, now pursued with genetically engineered pigs whose antigens and clotting proteins have been altered to survive in a human recipient."updated: "2026-07-27"updated: "2026-10-29"humanEvidence: "Two patients received gene-edited pig hearts and several others pig kidneys under compassionate use; every graft has failed or been removed within months, and formal kidney trials were cleared in 2025."humanEvidence: "Two patients received gene-edited pig hearts and several others pig kidneys under compassionate use; every graft has failed or been removed within months, and formal kidney trials were cleared in 2025."access: "No marketed product and no price: recipients so far have been patients ineligible for a human organ, treated under compassionate-use authorisation, with the first kidney trials cleared in 2025."access: "No marketed product and no price: recipients so far have been patients ineligible for a human organ, treated under compassionate-use authorisation, with the first kidney trials cleared in 2025."reversibility: "difficult"reversibility: "difficult"lines 36–42 → 36–4221 unchanged lines not shown
The driver is arithmetic. More than a hundred thousand people are on the United States transplant waiting list at any time, the great majority waiting for a kidney, and the US Health Resources and Services Administration puts the number dying each day while waiting at around seventeen. Waiting lists understate demand, because patients too sick or too old to qualify are never listed. The structural causes are set out in [[organ-shortage]], and no combination of donation reform, [[artificial-heart|mechanical support]] and improved organ preservation closes the gap.The driver is arithmetic. More than a hundred thousand people are on the United States transplant waiting list at any time, the great majority waiting for a kidney, and the US Health Resources and Services Administration puts the number dying each day while waiting at around seventeen. Waiting lists understate demand, because patients too sick or too old to qualify are never listed. The structural causes are set out in [[organ-shortage]], and no combination of donation reform, [[artificial-heart|mechanical support]] and improved organ preservation closes the gap. Non-human primates are immunologically closer but are slow-breeding, expensive, ethically fraught and carry viruses that cross to humans readily. Pigs breed fast, reach human organ size in months, tolerate genetic modification, and are already farmed at scale. Their organs are anatomically and physiologically similar enough that the remaining mismatches are addressable one gene at a time, which is the premise of the whole enterprise.Non-human primates are immunologically closer, but they breed slowly, are expensive and ethically fraught, and carry viruses that cross to humans readily. Pigs breed fast, reach human organ size in months, tolerate genetic modification, and are already farmed at scale. Their organs are anatomically and physiologically similar enough that the remaining mismatches are addressable one gene at a time, which is the premise of the whole enterprise. ## The immunological barrier## The immunological barrier lines 50–67 → 50–677 unchanged lines not shown
**Physiological mismatch.** Pig organs grow to pig proportions. Knocking out the growth hormone receptor limits this. Other mismatches, in erythropoietin signalling and in the renin-angiotensin system, are managed pharmacologically rather than genetically.**Physiological mismatch.** Pig organs grow to pig proportions. Knocking out the growth hormone receptor limits this. Other mismatches, in erythropoietin signalling and in the renin-angiotensin system, are managed pharmacologically rather than genetically. Two engineering strategies have emerged. Revivicor's animals carry ten modifications, four knockouts and six human transgenes. eGenesis, founded out of [[george-church]]'s laboratory, adds inactivation of the porcine endogenous retrovirus copies scattered through the pig genome, giving sixty-nine total edits. The PERV work grew out of demonstrations that dozens of retroviral copies could be knocked out at once in pig cells and then in live piglets, an early proof that [[crispr-cas9]] could be used at the edit counts previously seen only in the [[recoded-organisms|genome-recoding]] work on bacteria.[^yang2015][^niu2017] The same multiplex capability underlies the proxy-species programmes described in [[de-extinction]], and pigs are the animal in which it has been pushed furthest toward a product.Two engineering strategies have emerged. Revivicor's animals carry ten modifications: four knockouts and six human transgenes. eGenesis, founded out of [[george-church]]'s laboratory, adds inactivation of the porcine endogenous retrovirus copies scattered through the pig genome, giving sixty-nine total edits. The PERV work grew out of demonstrations that dozens of retroviral copies could be knocked out at once in pig cells and then in live piglets, an early proof that [[crispr-cas9]] could be used at the edit counts previously seen only in the [[recoded-organisms|genome-recoding]] work on bacteria.[^yang2015][^niu2017] The same multiplex capability underlies the proxy-species programmes described in [[de-extinction]], and pigs are the animal in which it has been pushed furthest toward a product. ## Development history## Development history ```timeline```timeline[[ { "year": "1963–1964", "title": "Primate era", "text": "Keith Reemtsma transplants chimpanzee kidneys, one recipient surviving nine months, and James Hardy places a chimpanzee heart in a dying patient. Immunology of the day cannot sustain the grafts." }, { "year": "1963-1964", "title": "Primate era", "text": "Keith Reemtsma transplants chimpanzee kidneys, one recipient surviving nine months, and James Hardy places a chimpanzee heart in a dying patient. Immunology of the day cannot sustain the grafts." }, { "year": "1984", "title": "Baby Fae", "text": "An infant with hypoplastic left heart syndrome receives a baboon heart at Loma Linda and lives 21 days. The case prompts lasting debate about consent and about experimental surgery in neonates." }, { "year": "1984", "title": "Baby Fae", "text": "An infant with hypoplastic left heart syndrome receives a baboon heart at Loma Linda and lives 21 days. The case prompts lasting debate about consent and about experimental surgery in neonates." }, { "year": "2003", "title": "Alpha-gal knockout pigs", "text": "Pigs lacking GGTA1 are produced, removing the antigen responsible for hyperacute rejection and making the modern programme possible." }, { "year": "2003", "title": "Alpha-gal knockout pigs", "text": "Pigs lacking GGTA1 are produced, removing the antigen responsible for hyperacute rejection and making the modern programme possible." }, { "year": "2018", "title": "Preclinical durability", "text": "A Munich group reports baboons surviving for months on life-supporting pig hearts using non-ischaemic preservation and blood-pressure control, establishing that the model can work." }, { "year": "2018", "title": "Preclinical durability", "text": "A Munich group reports baboons surviving for months on life-supporting pig hearts using non-ischaemic preservation and blood-pressure control, establishing that the model can work." }, { "year": "2021–2023", "title": "Decedent studies", "text": "Teams at NYU and Alabama transplant pig kidneys into brain-dead recipients maintained on ventilators, one for 61 days, to study early function without risk to a patient." }, { "year": "2021-2023", "title": "Decedent studies", "text": "Teams at NYU and Alabama transplant pig kidneys into brain-dead recipients maintained on ventilators, one for 61 days, to study early function without risk to a patient." }, { "year": "2022–2025", "title": "Living recipients", "text": "Two pig hearts and several pig kidneys are transplanted under compassionate-use rules, with survival measured in weeks to months, and US regulators clear the first formal kidney trials in 2025." } { "year": "2022-2025", "title": "Living recipients", "text": "Two pig hearts and several pig kidneys are transplanted under compassionate-use rules, with survival measured in weeks to months, and US regulators clear the first formal kidney trials in 2025." }]]`````` lines 99–105 → 99–10531 unchanged lines not shown
## Outlook## Outlook The decisive data should come from the cleared kidney trials, where recipients are less critically ill than the compassionate-use cohort and where survival can be compared against dialysis rather than against imminent death. The endpoint that matters is graft function at one year. Nothing in the human record yet approaches it, and the preclinical primate data suggest it is attainable.The decisive data should come from the cleared kidney trials, where recipients are less critically ill than the compassionate-use cohort and where survival can be compared against dialysis rather than against imminent death. The endpoint that matters is graft function at one year. Nothing in the human record yet approaches it, though the preclinical primate data suggest it is attainable. Three questions remain open. Whether the coagulation mismatch is fully corrected by the current transgene set, or merely delayed, will only be answered by grafts that survive long enough to develop chronic injury. Whether immunosuppression can be reduced to allograft-like levels, rather than the intensive experimental regimens used so far, determines whether the treatment is tolerable for patients who have a dialysis alternative. And whether a manufactured organ produced by a small number of firms is distributed any more equitably than donated ones is a question that the technology does not answer and that [[access-and-inequality]] raises for every expensive intervention.Three questions remain open. Whether the coagulation mismatch is fully corrected by the current transgene set, or merely delayed, will only be answered by grafts that survive long enough to develop chronic injury. Whether immunosuppression can be reduced to allograft-like levels, rather than the intensive experimental regimens used so far, determines whether the treatment is tolerable for patients who have a dialysis alternative. And whether a manufactured organ produced by a small number of firms is distributed any more equitably than donated ones is a question that the technology does not answer and that [[access-and-inequality]] raises for every expensive intervention. removed, struck through added, underlinedLine numbers count the serialised markdown of each revision, frontmatter included.
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