The ethical issues involved with xenotransplantation
Recently, there have been two examples of scientific innovation that are akin to science fiction. Gene-edited porcine organs were utilized for the first porcine-to-human organ transplants, providing evidence that xenotransplantation is now a much more viable idea than once supposed.
Clinical applications
The first study was published in the American Journal of Transplantation and detailed how brain-dead human recipients were utilized to test the safety of pig-to-human kidney transplants. The donor porcine were genetically modified, with a total of ten genes being edited. Four porcine genes were knocked out – GGTA1, β4GalNT2, CMAH and the porcine hormone growth receptor – and a total of six human genes were added. The knock-ins were: CD55, CD46, TBM, EPCR, HO1 and CD47. This study was one stage in continuing research conducted by the University of Alabama at Birmingham (AL, USA), who aim to carry out a Phase I clinical trial in which gene-edited kidneys are transplanted into living human beings. The novel preclinical model of utilizing brain-dead recipients proved useful, but the team ultimately concluded that further research is necessary to understand the long-term effects of such a practice.
Another, more recent, example of pig-to-human organ transplantation was conducted by doctors at the University of Maryland Medical Center (MD, USA). The doctors were granted special dispensation by the FDA to carry out the first procedure of its kind, a pig-to-human heart transplant. The patient was ineligible for a human transplant due to a history of non-compliance with medical instruction, he had been on cardiac support for two months and could not receive a mechanical heart because of an irregular heartbeat. The transplant was allowed to take place because it was asserted that he would otherwise face certain death. The patient lived for two months before passing away; the exact cause of his death has not been clarified.
Just because we can…
When asked by the BBC about the transplant, Maryam Khosravi, a postdoctoral research fellow at the University College London (UK) division of biosciences, stated: “animal to human transplantation has been something that we have studied for decades now, and it’s really interesting to see this group take that step forward.” She went on to add, “just because we can doesn’t mean we should” and maintained that there are still many unanswered questions. These procedures are undoubtedly ground-breaking and demonstrate just how far xenotransplantation has come, but they also illustrate the enormous risk that people can be exposed to.
We must ask ourselves, would this be routinely offered in a clinical setting? Julian Savulescu, Uehiro Chair in practical ethics at the University of Oxford (UK), stated: “you can never know if the person is going to die catastrophically soon after the treatment — but you can’t proceed without taking the risk. As long as the individual understands the full range of risks, I think people should be able to consent to these radical experiments.” Surgeons and scientists have a responsibility to patients and should be sure that the methods they are using are ready to be trialed. Attempting this kind of novel technique before it is ready could ultimately hurt prospective patients and end up proving as a setback for the field rather than a step forward. Clinicians who are testing this kind of novel procedure rely upon candidates to volunteer themselves to undergo experimental surgery. Misinformation can spread like wildfire when it comes to medicine, particularly a field such as gene editing which in itself can be viewed as controversial, so great care must be taken to ensure that people will trust the science, and trust those carrying out the transplants.
A monumental leap forward
Organ shortage is a crisis that is raging on and shows no sign of stopping. 17 people die every day while waiting for an organ transplant in the USA and there are currently over 100,000 people on the waiting list. This monumental problem demands a solution just as monumental. So, are pig-to-human transplants the answer? It would certainly be a convenient solution to be able to personalize the genetic edits made to the porcine organs to each patient and – we can only assume – this would result in more organ transplants taking place, which would be an extremely positive step.
There are a whole host of societal factors that make organ donation a difficult and slow process, so it is no wonder that science looks to non-human donors. One thing is certain, something needs to be done and with a shortage of human tissue available, scientists have long been looking to porcine for the solution. For example, porcine valves are routinely used in aortic valve replacements on the NHS in the UK. When discussing the pig-to-human kidney transplants, Robert Montgomery (NYU Langone Health; NY, USA), one of the surgeons involved in the research, expressed that he could understand people feeling hesitant about these kinds of procedures. But he also added that “currently about 40% of patients who are waiting for a transplant die before they receive one…. we use pigs as a source of food, we use pigs for medicinal uses — for valves, for medication. I think it’s not that different.”
This little piggy
Porcine have been selected by both the USA and the UK as the animal of choice when it comes to xenotransplantation. This is largely due to the fact that porcine organs, particularly the heart, are the same relative size to humans and that porcine can be easily raised. A potential hazard, which some scientists have warned against, is porcine endogenous retroviruses, which are integrated into the genome of all porcine and may be capable of infecting human cells. Bernard Rollin, Emeritus Professor of Philosophy, Animal sciences and Biomedical sciences at Colorado State University (CO, USA), stated in the journal Animals: “some of these diseases may spread ‘horizontally’ across a community, serving as a danger to public health. This is a potential risk, although, it has not been observed in clinical trials when transplanting porcine islet cells into diabetic humans.
One cannot explore this topic without discussing animal welfare. The porcine currently being utilized for xenotransplantation are raised by Revivicor (VA, USA) and have been approved by the FDA. In a 2020 document, Revivicor expressed that “the facility and staff maintain high standards of animal welfare during the entire lifespan of the pig.” They also emphasize that the facility undergoes regular inspection and is reaccredited every 3 years. Janine McCarthy, medical researcher at the Physicians Committee for Responsible Medicine (DC, USA), a not-for-profit organization that carries out clinical research, disagrees, and has stated that, “xenotransplantation wastes time, money, and lives, we must develop plausible strategies for addressing heart disease rather than pursuing the dystopian use of pig hearts for xenotransplantation.” Whether or not the Revivicor publication puts your mind at ease, the animal welfare aspect simply is not something that can be ignored. However, it could be argued that the meat industry is just as, if not more, problematic. The porcine kidneys are being used to enact lifesaving surgery, which could provide quality of life for those that desperately need it.
A routine solution
Whatever side of the fence you have settled on, this is a remarkable leap forward. The organ shortage is a problem that is not going away, and it could be asserted that porcine donors make for a more practical solution. Whether or not that is true, pig-to-human heart transplants are far from becoming routine, but this research certainly demonstrates that we might not be as far away from this as expected.
Sources:
Manesh S, Samani R, Manesh S. Ethical Issues of Transplanting Organs from Transgenic Animals into Human Beings. Cell. 16(3) 353—360 (2014).
Rollin B. Ethical Issues of Transplanting Organs from Transgenic Animals into Human Beings. Animals. 10(9) (2020).
GalSafe® Pigs Environmental Assessment. Revivicor. VA, USA (2020).
First pig-to-human heart transplant: what can scientists learn? https://www.nature.com/articles/d41586-022-00111-9?msclkid=b9775f76aab611eca46d0732e960ba9d [Accessed 24 March 2022].
Man gets
genetically-modified pig heart in world-first transplant. https://www.bbc.co.uk/news/world-us-canada-59944889 [Accessed 24 March 2022].
One Very Bad Idea, Two Victims. https://www.pcrm.org/news/good-science-digest/one-very-bad-idea-two-victims?msclkid=96ec9190aac411eca1e27ac600b1f66a [Accessed 24 March 2022].
Organ Donation Statistics. https://www.organdonor.gov/learn/organ-donation-statistics?msclkid=92d01acbaf6511ec837c15783d3287c0 [Accessed 6 April].
US surgeons test pig kidney transplant in a human. https://www.bbc.co.uk/news/health-58993696?msclkid=9a74c41aaab611ec95ed8d52edc2f640 [Accessed 24 March 2022].
Three ethical issues around pig heart transplants. https://www.bbc.co.uk/news/world-59951264?msclkid=d92ab9c2aab611ecb51ca30469a0af69 [Accessed 24 March 2022].
Harriet Stanwix
Harriet is the Assistant Editor of RegMedNet and author of this article. She ensures that the site is up-to-date with the latest news and industry developments. With a degree in English Literature and Language and experience working as a Medical Editor, Harriet is excited to bring a fresh take on regenerative medicine. She also has a keen interest in the latest innovations in cell and gene therapy and is interested in the ethical issues within the field of regenerative medicine.