Written by Christine Kuang
Edited by Jacquelyn Tang
Human organs are scarce. Why not order organs from animals?
According to the American Transplantation Foundation, there are currently 107,000 patients on the waiting list. Clinical transplantation functions as an end-stage organ failure solution. This astronomical number does not include patients whose surgeries have not met the criteria of "lifesaving." Due to the shortage of human organs supply, the waiting list for organ transplantation is brutally long and can take years before one is matched. However, there is one solution to the supply-demand imbalance - Xenotransplantation.
Xenotransplantation is the medical technique of grafting or transplanting non-human organs or tissues and can offer immediate relief to the scarcity of human organs.
This idea is not new; half-man and half-beast chimeras exist through folklore and ancient Egyptian gods (Deschamps, Roux & Gouin, 2005). Xenotransplantation was first performed with cells and tissues; however, as medicine evolved, our techniques to control bleeding and circulation after transplantation gave rise to the possibility of more successful xenotransplantation.
Below is a timeline of xenotransplantation (Mitra, 2018):
In 1667, a French physician Jean-Patiste Denys, performed a blood transfusion of a lamb to a 15-year-old boy, curing the patient.
In the 19th century, skin grafts from frogs were performed.
In 1838, Dr. Kissam performed pig-to-human corneal xenotransplantation; the pig did not survive.
In 1963, Dr. Keith Reemtsma transplanted chimpanzee kidneys to thirteen patients; the patients did not survive.
In 1964: Dr. James Hardy performed the first lung transplant using a chimpanzee heart; the patient did not survive.
In 1983, Baby Fae received a baboon's heart; the patient died twenty-one days later.
In 1992, Dr. Starzl transplanted a baboon's liver to a human; the patient died seventy days later.
In 1997, Dr. Dhani Ram Baruah was jailed for the transplantation of a pig heart to a human without the patient's consent; the patient died seven days later.
21st Century: The FDA statement on xenotransplantation on (CRISPR)-Cas 9 and genetic engineering technology suggests that "transplantation of cells and tissues may be therapeutic for certain diseases such as neurodegenerative disorders and diabetes, where, again human materials are not usually available."
One notorious xenotransplantation procedure was done in 1983 on Stephanie Fae Beauclair, a premature twelve-day-old infant. Baby Fae was born with hypoplastic left heart syndrome, a serious birth defect that affects blood flow in the heart. With an immense scarcity of (human) infant organs, Baby Fae was the first infant to undergo a heart transplant receiving the heart of a baboon. On October 26, 1984, Dr. Leonard L Bailey lowered Stephanie's body temperature to 68°F and transplanted the anesthetized seven-month-old baboon's heart to Stephanie (Stafford, 2019). After her procedure, the surgical team successfully closed her chest cavity, and Stephanie's body temperature slowly rose back to normal. However, Baby Fae passed away 21 days after the procedure from heart failure.
Baby Fae died from organ rejection of her baboon heart. One issue with the surgical procedure was the blood type incompatibility. Baby Fae is Blood Type O. The baboon's heart was Blood Type AB. Medical personnel could not find a suitable baboon donor given the short time span and urgency of the medical case. However, it is worth noting that Baby Fae outlived most infants born prematurely with hypoplastic left heart syndrome by 1-2 weeks. Her case divided the medical community and enraged animal rights activists for playing with both human and animal lives.
How does xenotransplantation work? In an example of a pig to human xenotransplantation, the most acceptable and popular xenotransplantation done is that of pig tissue. There are some key similarities between our body and a pig, such as organ size. Medical doctors have replaced damaged human heart valves with pig valves, using glutaraldehyde to preserve the pig's heart valve. Due to the complexity of the cross-species immune system, immunosuppression is necessary to prevent our antibodies from rejecting a new organ or tissue. Thus, the feasibility of this procedure includes a range of "immunosuppression treatment with azathioprine, actinomycin C, prednisone, and total body irradiation" and "plasmapheresis" with records of deaths not related to xenotransplantation gave more sound evidence of further studies (Deschamps, Roux & Gouin, 2005).
What is the risk and difficulties of xenotransplantation? Our immune system may be susceptible to cross-species transmission of porcine endogenous retroviruses (PERVs), cross-species infections. For example, "pigs have been the source of significant zoonotic infections of humans, including fatal cases of swine influenza attributed to the swine influenza virus" (Boneva, Folks, and Chapman, 2001). Furthermore, immunologic rejection can also occur with "The galactose alpha-1,3-galactose epitope on the vascular endothelium surface of pigs is a major obstacle to successful xenotransplantation" (Cooper, 2016). Our antibodies will attack the foreign implanted tissue or organ even with immunosuppression. Furthermore, nonspecific immunosuppression is not stable with "severe toxicity" to non-human primates (Yang & Sykes, 2007). There are additional difficulties in findings and matching the non-human organ to that of the human patient, differences in physiology, organ size compatibility, and problems in genetically breeding animals (Yang & Skykes, 2007). One major limitation of xenotransplantation is that there has been no long-term successful xenogeneic graft documentation but a short-term extension to viability.
Researchers today are examining antibody binding and coagulation dysfunction to prevent triggering the human leukocyte antigen (HLA) cross-species organ rejection. Today's (CRISPR)-Cas 9 technology to perform gene knock-out and knock-in of genetically engineered animals through homologous recombination during its embryology can potentially evolve our xenotransplantation procedures and success rates (Ekser, Li, Cooper, 2018).
Biblical teachings and animal rights activists are strong advocates against this procedure. However, our consciousness creates second thoughts on this procedure. Is this medical practice ethically justified? Do human lives constitute more value than animals? Do we want to genetically engineer animals to be compatible with human genes and insert animal organs inside us? Until these significant obstacles are solved, will xenotransplantation become more popular?
Although xenotransplantation pre-clinical research is premature, it may serve as a second option perspective on the future of transplantation. Will you be willing to accept a cross-species organ?
Yang, Yong-Guang, and Megan Sykes. “Xenotransplantation: Current Status and a Perspective on the Future.” Nature Reviews Immunology, vol. 7, no. 7, July 2007, pp. 519–31. www.nature.com, https://doi.org/10.1038/nri2099.
Deschamps, Jack-Yves, et al. “History of Xenotransplantation.” Xenotransplantation, vol. 12, no. 2, 2005, pp. 91–109. Wiley Online Library, https://doi.org/10.1111/j.1399-3089.2004.00199.x.
Dec 16, Naresh Mitra |. TNN |. Updated:, et al. “In 1997, This Indian Doctor Tried Pig Heart Transplant, Was Jailed - Times of India.” The Times of India, https://timesofindia.indiatimes.com/home/science/in-1997-this-indian-doctor-tried-pig-heart-transplant-was-jailed/articleshow/67111349.cms. Accessed 18 Oct. 2021.
Stafford, Ned. “Leonard L Bailey: In 1984 He Transplanted a Baboon Heart into a Human Infant Known as ‘Baby Fae.’” BMJ, vol. 366, July 2019, p. l4669. www.bmj.com, https://doi.org/10.1136/bmj.l4669.
Cooper, David K. C. “Modifying the Sugar Icing on the Transplantation Cake.” Glycobiology, vol. 26, no. 6, June 2016, pp. 571–81. PubMed Central, https://doi.org/10.1093/glycob/cww028.
Ekser, Burcin, et al. “XENOTRANSPLANTATION: PAST, PRESENT, AND FUTURE.” Current Opinion in Organ Transplantation, vol. 22, no. 6, Dec. 2017, pp. 513–21. PubMed Central, https://doi.org/10.1097/MOT.0000000000000463.
Research, Center for Biologics Evaluation and. “Xenotransplantation.” FDA, 3 Mar. 2021, https://www.fda.gov/vaccines-blood-biologics/xenotransplantation.
Boneva, Roumiana S., et al. “Infectious Disease Issues in Xenotransplantation.” Clinical Microbiology Reviews, vol. 14, no. 1, Jan. 2001, pp. 1–14. PubMed Central, https://doi.org/10.1128/CMR.14.1.1-14.2001.
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