Jessica Penna, 11th Grade

Solid organ transplantation, the only remedy to end-stage organ failure, is a relied upon practice for thousands of patients every year. Whether it be for kidneys, lungs, livers, or hearts, a patient can only get new organs through donation from a healthy patient or, from the most frequent source, a brain dead (BD) patient (1)(2). However, reliance on BD patients for transplantable organs proves quite difficult considering that only 2.06% of deaths in the US are from brain death, and as a result there is a universal shortage of available organs for transplant (3). In the US alone, there were more than 100,000 people in need of a kidney transplant on the waiting list at the start of 2019, and yet there were only 24,273 transplants performed the previous year (4). It is even estimated that 10% of patients on the waiting list die before being able to receive treatment (1).

With an ever increasing supply and the inability to meet demands, the newly developing field of xenotransplantation is viewed as a promising alternative. Through xenotransplantation, modern medicine can transplant cells, tissues or organs from an animal, most commonly from pigs, to a human. Many trials in the 20th century originally included the use of nonhuman primates (NHPs) for organ testing due to their close evolutionary lineage to human beings, but pigs were eventually determined as the animal of choice due to their larger litter sizes, close physiological similarities to human organs, and shorter gestation periods (5)(6). Even so, many larger problems still remained in regards to graft rejection and disease risks. Hyperacute, or immediate, rejection can occur within minutes to hours of a graft transplant due to the breakdown of foreign antigens from the porcine, or pig, organs by the host’s natural antibodies (7). Another major concern included the porcine endogenous retroviruses (PERVs) deeply integrated into porcine genomes which are greatly transmissible through xenotransplantation (5). Though major risks were increasingly apparent, a scientific breakthrough in 2012 by scientists Emmanuelle Charpentier and Jennier A. Doudna changed everything as researchers could now accurately and reliably modify specific cell DNA through their CRISPR-Cas9 technology. With this, possibilities became real as pig organs genetically modified for the purpose of xenotransplantation could avoid invasion from the natural antibodies present in human and NPH hosts (8). This technology also facilitated the removal of PERVs from the porcine genome, and in accordance with the sterile environments in which the pigs are raised, the animals have become increasingly viable for clinical xenotransplantation as risk of disease decreases (5).

However, the debate of animal ethicacy is brought into question when discussing the pigs’ aforementioned sterilized environments. Though PERVs are greatly regulated through CRISPR-Cas9 genetic modification, the risk of disease transmitted from animal to human transplants, or xenozoonosis, is still a dangerous possibility (5). If not regulated properly, porcine pathogens could not only affect the individual receiving treatment, but many others in society as well (9). A single infected patient can easily spread deadly zoonotic diseases to dozens of others as previously displayed through instances such as the Swine Flu epidemic in 2009 and the 1976 Ebola outbreak in Zaire (6)(9). As the FDA attempts to limit these outbreaks, several clinical protocols have been enforced in regards to xenotransplantation research to greatly reduce pathogenic exposure to laboratory pigs (10). These mandates, though for the purposes of relatively safe transplantations, confine animals into sterilized enclosures that minimally accommodate their telos, or behavioral and physiological natures. Pig health may be maintained, but the animals’ overall welfare as living beings is reduced as they are raised in environments to which they are not naturally suited (6).

Even as pigs may be limited under sterilized conditions, a greater occurring debate discusses the morality of cultivating animals for the purpose of harvesting their organs. In terms of animal numbers, refining clinical xenotransplantation for commercial use will lead to the mass production of thousands of pigs for organ donation, but the processes of farming these animals would prove quite similar to cultivating livestock for consumption (9). Pigs are slaughtered regularly to supply the general public with pork-based goods, and in 2016 nearly 1.5 billion pigs were killed worldwide (11). Even if pig deaths increase for the purposes of xenotransplantation, thousands of lives could be saved as a result (6).

As genetically modified porcine organ technology continues to progress, clinical xenotransplantation has become even more palpable as the first successful heart xenotransplant was performed in the United States on January 7th 2022. The patient, 57-year-old David Bennett, had been suffering from terminal heart failure but was ineligible for solid organ transplant, and with no other options present, the FDA approved the cardiac team’s application to proceed with experimental xenotransplantation. The patient’s porcine heart showed no signs of rejection and was working smoothly, but approximately 2 months after the procedure on March 9th 2022, David Bennett passed away (8). Though a monumental step in terms of xenotransplant development, controversy erupted as the patient’s criminal record came to light. Charged with attempted murder at age 23, Bennett was convicted for repeatedly stabbing a young 22-year-old man in 1988, leaving the victim paralyzed from the waist down. It was claimed in a written statement by the hospital officials that a patient’s background doesn’t determine whether or not they receive lifesaving care, but the victim’s family felt otherwise (12).

Xenotransplantation is looking towards the future for a greater prepared tomorrow and continues to advance (5). Through harnessing organs from genetically modified pigs, modern trials are overcoming previous complications of graft rejection and are taking steps to avoid xenozoonosis transmissions (5)(8). To ensure the health of patients, pigs are maintained in sterilized environments approved by the FDA, even if they restrict the pigs’ traditional animal natures (6)(10). Many ethical debates continue to arise, but recent successes give great potential to xenotransplantation as a major remedy to the universal organ crisis.

Citations:

(1) D. Escudero, et al., Organ Donation and Elective Ventilation: A Necessary Strategy.
BioMed Research International 2017 (2017).
(2) Black, C. Black, et al., Solid Organ Transplantation in the 21st Century. Annals of
Transplantation Medicine 6,20 (2018).
(3) M. Abounakr, et al., Brain Death Criteria. StatPearls, (2021).
(4) J. Miller, et al., Impact of COVID-19 Pandemic on the Size of US Transplant Waiting Lists. Clinical Transplantation 36,5 (2022).
(5) L. Tianyu, et al., Xenotransplantation: Current Status in Preclinical Research. Frontiers in Immunology 10 (2022).
(6) B. Rollin. Ethical and Societal Issues Occasioned by Xenotransplantation. Animals
10,9 (2022).
(7) J. Boulet, et al., Cardiac Xenotransplantation: Challenges, Evolution and Advances.
JACC: Basic to Translational Science (2022).
(8) S. Aakash., H. Jason., First Successful Porcine to Human Heart Transplantation
Performed in the United States, Artificial Organs 46, 543-545 (2022).
(9) S. Dyer, Ethical Ramifications of Xenotransplantation Research and Justification for Potentially Deadly Study Participation. Duquesne Scholarship Collection (2022).
(10) US Food and Drug Administration, Source Animal, Product, Preclinical, and Clinical Issues Concerning the Use of Xenotransplantation Products in Humans, US Department of Health and Human Services (2016).
(11) B. Sanders, Global Pig Slaughter Statistics and Charts, Faunalytics, (2018)
(12) L. Johnson., W. Wan., “The Ethics of a Second Chance: Pig Heart Transplant Recipient Stabbed a Man Seven Times Years Ago”, The Washington Post, (2022).