Xenotransplantation concerns the transplantation of an organ or tissue of a given type of animal to another type of animal or to a human being. This type of transplantation has gained interest because of the shortage of human organ donations. In the Netherlands, xenotransplantation from animals to humans is prohibited. [1: Wet van 24 oktober 1997, houdende regels betreffende bijzondere verrichtingen op het gebied van de gezondheidszorg (Wet op bijzondere medische verrichtingen). Staatsblad van het Koninkrijk der Nederlanden, 1997, 515.] In an exploratory dialogue, there does seem to be support among the Dutch population to further investigate xenotransplantation under conditions to eventually allow it. [2: Y.E. Willems, I.S. Pirson, J. Gouman and J. Verhoef. Het dier als donor – Een maatschappelijke dialoog over het gebruiken van dieren voor orgaantransplantatie bij de mens. Den Haag: Rathenau Instituut, 2022.]

At the end of the 20th century there was great enthusiasm about xenotransplantation, especially because of a few noted successes: a Chimpanzee kidney was only rejected after nine months, and a Baboon heart was rejected in a human baby after a few weeks. In general, those successes were limited and the enthusiasm had dwindled at the beginning of the 21st century [3: G. Blancho. Editorial xenotransplantation. Curr Opin Organ Transplant. 2009/03/21 ed 2009, 14, 147 doi:10.1097/MOT.0b013e3283292595.]. In particular, the exposure of immunogenic antigens on the animal donor tissue was found to elicit more rejection reactions than hoped for. These rejection reactions were also found to be less easily treated than when the organs came from human donors. Getting this problem under control was, however, a prerequisite for obtaining a usable graft survival. The chosen solution direction involved the genetic modification of donors, mostly pigs [4: D.K.C. Cooper, R. Gaston, D. Eckhoff, J. Ladowski, T. Yamamoto, L. Wang, H. Iwase, H. Hara, M. Tector and A.J. Tector. Xenotransplantation-the current status and prospects. Br Med Bull. 2017/12/12 ed 2018, 125, 5-14 doi:10.1093/bmb/ldx043.] Genetic modification has been easier since 2014 with the introduction of the CRISPR-cas9 technique. The first human xenotransplantation successes were expected with transplantation of genetically modified cells derived from pig islets of Langerhans. [5: D.K.C. Cooper, R. Gaston, D. Eckhoff, J. Ladowski, T. Yamamoto, L. Wang, H. Iwase, H. Hara, M. Tector and A.J. Tector. Xenotransplantation-the current status and prospects. Br Med Bull. 2017/12/12 ed 2018, 125, 5-14 doi:10.1093/bmb/ldx043.] In 2022, however, a man in Maryland (USA) received a heart from a cloned pig in which 10 genes had been modified. [6: B.P. Griffith, C.E. Goerlich, A.K. Singh, M. Rothblatt, C.L. Lau, A. Shah, M. Lorber, A. Grazioli, K.K. Saharia, S.N. Hong, S.M. Joseph, D. Ayares and M.M. Mohiuddin. Genetically Modified Porcine-to-Human Cardiac Xenotransplantation. N Engl J Med. 2022/06/23 ed 2022, 387, 35-44 doi:10.1056/NEJMoa2201422.] The initial course was prosperous. After 49 days, severe thickening of the heart muscle developed; 60 days after transplantation, the patient died. At autopsy, necrosis (death) of cardiac myocytes was seen. The cause was multifactorial: rejection, an immune response to the administered human immunoglobulins and activation of porcine CMV virus. [7: M.M. Mohiuddin, A.K. Singh, L. Scobie, C.E. Goerlich, A. Grazioli, K. Saharia, C. Crossan, A. Burke, C. Drachenberg, C. Oguz, T. Zhang, B. Lewis, A. Hershfeld, F. Sentz, I. Tatarov, S. Mudd, G. Braileanu, K. Rice, J.F. Paolini, K. Bondensgaard, T. Vaught, K. Kuravi, L. Sorrells, A. Dandro, D. Ayares, C. Lau and B.P. Griffith. Graft dysfunction in compassionate use of genetically engineered pig-to-human cardiac xenotransplantation: a case report. Lancet. 20230629 ed 2023, 402, 397-410 doi:10.1016/S0140-6736(23)00775-4.] In 2023, a kidney from the same genetically modified pig species remained functioning properly for a week in a brain-dead patient with renal insufficiency. After a week, support (including ventilation) of the brain-dead patient was discontinued. The kidney transplant was functioning very well at that time and no signs of rejection were visible under the microscope either. [8: J.E. Locke, V. Kumar, D. Anderson and P.M. Porrett. Normal Graft Function After Pig-to-Human Kidney Xenotransplant. JAMA Surg. 20230816 ed 2023 doi:10.1001/jamasurg.2023.2774.] This result possibly means that xenotransplantation with organs from genetically modified animals has moved closer to application in humans.

In addition, in xenotransplantation, the transmission of animal viruses to human beings proves to be a clear risk [9: L. Scobie and Y. Takeuchi. Porcine endogenous retrovirus and other viruses in xenotransplantation. Curr Opin Organ Transplant. 2009/05/27 ed 2009, 14, 175-179 doi:10.1097/mot.0b013e328327984d.]. Also with regard to this problem, genetic modification using the CRISPR-cas9 technique is hoped to move forward: viruses present in DNA could be “cut” out of the DNA using this technique. The genetically modified pigs used in 2022 and 2023 would not carry the porcine endogenous retrovirus. Nevertheless, the porcine-CMV virus appeared to be transmitted and less treatable than the human equivalent. [10: B.P. Griffith, C.E. Goerlich, A.K. Singh, M. Rothblatt, C.L. Lau, A. Shah, M. Lorber, A. Grazioli, K.K. Saharia, S.N. Hong, S.M. Joseph, D. Ayares and M.M. Mohiuddin. Genetically Modified Porcine-to-Human Cardiac Xenotransplantation. N Engl J Med. 2022/06/23 ed 2022, 387, 35-44 doi:10.1056/NEJMoa2201422.]

In 2001, the Pontifical Academy for Life dedicated a symposium to this subject, in order to respond to a number of questions of a moral nature with respect to xenotransplantation. The symposium highlighted, first of all, three anthropological and ethical issues relevant to the question of whether xenotransplantation, as such, is a good act [11: Pontifical Academy for Life. Prospects for xenotransplantation scientific aspects and ethical considerations. Vatican City 2001.]:

1. The acceptability of human intervention in the created order.
2. The ethical acceptability of using animals to increase the Medical Care for Life: Therapeutic Interventionchance of survival of human beings and to increase their wellbeing.
3. The possible objective and subjective influence which an organ or tissue of animal origin can have on the identity of the human recipient.