David Bennett, 57, recently became the first human being ever to be transplanted with a pig’s heart. He had the operation done in Baltimore, Maryland, on 7 January 2022 using a genetically modified heart. We asked our panel members if they would consider xenotransplantation as an option for their patients.
The organ, under the name Uheart™ (xenoheart), was developed by US firm United Therapeutics Corporation – Revivicor and had a total of 10 genes modified or deactivated. Doctors hope that these deactivations will prevent an aggressive immune response in the recipients’ body and the chances of acceptance will be increased. They are also developing a kidney xenotransplantation option named UKidney™ (xenokidney) which is also showing interesting progress.
The United States Food & Drug Administration (FDA) defines xenotransplantation (also known as a heterologous transplant) as “any procedure that involves the transplantation, implantation or infusion into a human recipient of either:
- live cells, tissues, or organs from a nonhuman animal source,
- human body fluids, cells, tissues or organs that have had ex vivo contact with live nonhuman animal cells, tissues or organs.”
It involves the transplantation, implantation, or infusion of cells, tissues, or organs among different species, and would be used only for patients with end-stage cardiac, respiratory, or hepatic failure, when the only chance of survival is a transplant.
And how does xenotransplantation work?
Medical science already uses animal parts for various therapeutic reasons, such as replacement heart valves from pigs. However, these therapeutic products have been chemically treated and are not functional, living tissue. This distinguishes them from the viable organs used in xenotransplantation. Organ xenotransplants could include whole hearts, lungs, livers, kidneys or pancreases. Tissue xenotransplants could include skin grafts for burn patients, corneal transplants for the visually impaired, or bone transplants for limb reconstruction. Cellular xenotransplants may provide treatment for people with diabetes, Alzheimer’s or Parkinson’s diseases.
The most significant issue with using animals for a source of transplanted organs (xenotransplantation) for humans is immunological rejection of the organ, with the human immune system recognizing the foreign organ as “not-self” and correlatively rejecting it. In what is known as “hyper-acute rejection”, the body begins to reject the organ virtually as soon as it is implanted.
In the case of genetically engineered pigs, however, a small amount of human genetic material can be injected into the developing pig embryo, so that the resulting piglet is not recognized as foreign. Then, the use of immune-system-suppressing drugs helps in reducing the probability of rejection.
What did our panel members think about xenotransplantation?
We asked our panel members if they would consider xenotransplantation as a viable treatment option for their patients, and from the 6715 M3 panel members who took part in the survey, only 10% of respondents said they wouldn’t recommend xenotransplantation to their patients. However, half of them think that the concept of xenotransplantation seems promising.
The majority of respondents are in favor of xenotransplantation, with 85% of total respondents considering it as a viable treatment option, however, 45% of total respondents would only consider recommending it to their patients as a last resort.
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Xenotransplantation pros and cons
- prevent the death of patients in need of transplants because of no available organs for transplantation.
- provide an unlimited supply of cells, tissues, and organs for humans.
- add new treatment options for many diseases.
- immune rejection, uncertain efficacy/viability, and whether high levels of immunosuppression will leave the patient vulnerable to more frequent infectious diseases or cancer.
- infection of recipients with both recognized and unrecognized infectious agents and the possible subsequent transmission to the community.
- cross-species infection by retroviruses, which may be latent and lead to disease years after infection. The worst-case scenario would be a major new epidemic.
A brief history of xenotransplantation
Then skin xenografts became popular in the 19th century using many species as donors, including rabbits, dogs, and pigeons. Medical historians believe that none of the grafts became permanent and just aided the wound healing by covering the skin and protecting the ulcer beneath.
Between 1963 and 1964, Professor Keith Reemtsman carried out 13 chimpanzee-to-human kidney transplantations, where none of the patients survived. And in the late 1980s Dr. David Cooper, a heart transplant surgeon, began arguing that pigs were the best donors for human transplantation, mostly based on the size of the organ. In the next decade, the Cooper lab identified one of the main components in porcine cells that trigger the human immune response, opening the door to the first genetically modified pigs.
More information about the history of xenotransplantation.
Ethics of xenotransplantation
In Bernard E. Rollin’s paper, ‘Ethical and Societal Issues Occasioned by Xenotransplantation’, we find that the ethical discussion around xenotransplantation revolves around three issues:
- Ethical tension between the good of the recipient and the good of society. It’s clear that xenotransplantation could be the only choice for a transplant patient when there are no human donors, but does the live of this individual outweighs the risk of endogenous retroviruses carried by pigs to probably cause a new major pandemic?
- Animal welfare issues. The ethical issue of concern to the majority of society is not the killing of animals, although it will be to some. Rather, what troubles society in general is the condition of how the animals live, and the unnatural conditions under which they are housed and maintained. Pigs raised for organ transplantation are kept much in the manner of laboratory animals, under confined, sterile conditions that minimize the risk of pathogen proliferation and keep the animals sufficiently healthy to provide a safe source for transplantation.
- Opposing views to genetic engineering based on beliefs. This issue revolves around the claim that humans shouldn’t be meddling with genetic engineering, many times based on religious beliefs because it goes “against nature”, or non-rational concerns.
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