In 2022, the world’s first pig heart-to-human heart clinical procedure was successful, opening a new chapter in human organ transplantation. In the United States, nearly 8,000 patients waiting for organ transplants die each year. And in China, the number of patients waiting for organ transplantation is close to 2 million. During the long wait, many patients say goodbye to the world with regret. Xenogeneic transplantation (xenogeneictransplantation or xenotransplantation) is the transplantation of tissue or organs between two individuals of different biological species. For example, tissue (e.g., skin) or organs (e.g., heart, kidney, lung) from a primate (e.g., chimpanzee or baboon) are transplanted into a human. Xenotransplants are classified into ConcordantXenograft, such as ape and human, and DiscordantXenograft, such as pig and human, depending on the difference in the ethnic genetic background of the donor-recipient and the degree of immune rejection that occurs. As with other organ transplants, lung transplantation faces a serious supply-demand imbalance, which can be addressed in several ways: increasing cadaveric donation, using living donors, developing portable respiratory support devices, tissue engineering and xenotransplantation. Increasing cadaveric donations is currently the primary method of increasing the source of donor lungs adopted by many countries, and with modest success. But even a twofold increase in cadaveric organ recovery in each country (which is unlikely to be achieved for a variety of reasons) would not meet the potential demand. Researchers in several countries have done detailed assessments and concluded that the demand would not be met if every potential donor’s organs could be utilized for transplantation. Only 4% of the organs of deceased patients who die in hospitals are suitable for transplantation, so it is unlikely that the number of organs donated cadaverically each year will increase significantly. Experience with the use of living donor-supplied lung lobes for transplantation is increasing, and this type of transplantation may be more appropriate for children because the number of donor lungs in children is smaller than the number of patients requiring transplantation, the amount of lung tissue needed in children being considered for lobar transplantation is not well understood, and it is not clear whether the transplanted lobes will grow with the child. Adult lung lobes transplanted into pigs do grow in size with the pigs. The exploration of living donors offers an opportunity for children with severe lung disease, but this measure is also a dilemma, as lobectomy is much more dangerous and deadly than nephrectomy. Extracorporeal membrane oxygenation (ECMO) has made great progress in the last decade or so, but it can only be used as a temporary adjunctive therapy and cannot replace the lung in the long term. ECMO-derived technologies (e.g., in vivo artificial lung) are now being developed, but the challenges of oxygenation efficiency, biocompatibility, and anticoagulation effects have not yet been overcome, and it is estimated that such devices will not be available for clinical use in the next 10 years. . Tissue engineering to construct lung tissue, placing stem cells into scaffold materials and inducing differentiation and cell culture to make lung tissue, research on tissue engineering is still in its infancy, and it is not yet possible to construct complete lung tissue. Xenotransplantation, using animals from the human side to transplant their organs into the recipient, is a promising approach. Because the animals currently utilized for xenotransplantation are mainly pigs, this would provide an unlimited source of donors for humans. Currently xenograft lung transplantation is limited to animal experiments and survival time rarely exceeds a few hours. There are currently over 4,000 mammalian species on the planet, very few of which could potentially be used for xenotransplantation. The selection of donor animals must meet the following principles: 1. be available in large numbers and relatively inexpensive; 2. be easy to raise and manage; 3. have anatomical, physiological and biochemical metabolic similarities to humans; 4. be guaranteed not to transmit disease; and 5. be acceptable to the public. The choice of which animal or genus of animal can be used as a long-term donor for xenotransplantation is still controversial. There is no doubt that the most suitable animals for xenotransplantation are other primates, such as chimpanzees, baboons, and monkeys, that do not include humans. However, these animals are not routinely used as donors for xenotransplantation for the following reasons: the number of such animals is limited, especially in large primates such as chimpanzees. The average female baboon or chimpanzee takes 7 or 12 years, respectively, to reach reproductive age. After giving birth, baboons need at least 2 years to nurse their offspring, and chimpanzees up to 6 years; neither can become pregnant again during this period. Therefore, it takes at least 70 years, if not 100 years, to reach the age where they can be used as transplant animals, which inevitably increases the cost of organ transplantation significantly. At the same time, monkeys and even baboons appear to be small compared to humans. The best source of allogeneic lung transplant donors is the pig, which has the following advantages: (1) the size of homozygous organs is basically the same as that of humans, and the growth period is also basically the same; (2) it is distantly related to humans, and the chance of transmitting diseases is small; (3) the gestation period is short, the number of litters is high, reproduction is fast, and offspring growth is fast; (4) genetic engineering can be used to add genes to the genome or remove a gene, and genetic modification in cultured cells is easier than experimenting on the whole animal. It is much easier to perform genetic modifications in cultured cells than to experiment on whole animals, and their gene expression can be regulated at the post-transcriptional level using molecular biology methods. What is the psychological and physiological resilience of the recipient preparing to receive an animal organ in the face of the enormous impact of ethical and moral social issues? How is this perceived by the existing society and what kind of environment will his offspring grow up in? Is it still human to use various “animal parts” to put together? There are many other difficult questions that humans have to face: is the right and dignity of life being manipulated, and is life worth prolonging at all costs? Do we have the right to alter the laws of natural selection? Whether the rights of animals should be taken into account, etc., are difficult to answer in the current ethical system. Since the development of science and technology has its own laws, the boundary of ethics is not destined to be the end of the development of science and technology, and the reconstruction of social ethics and conceptual system may only be a matter of time. Faced with attractive development prospects and a wide commercial market, xenotransplantation has attracted the interest of more and more governmental and commercial organizations, and its research progresses day by day. While the desire for treatment continues to be fulfilled, there is also concern about its potential risks. At a conference organized by WHO, several clinicians, ethicists and others discussed the ethical, benefit and safety aspects of tissue and organ transplantation, among other global concerns. The meeting concluded that xenotransplantation has the potential to complement the limited supply of human material for transplantation and may even be an alternative option, but warned that xenotransplantation such as the use of live animal allogeneic cells, tissues or organs may pose specific immune problems for the recipient. The public health impact and the importance of public health surveillance after xenotransplantation were emphasized especially after the outbreak of the animal-derived SARS epidemic in 2002. In terms of the feasibility of animal-human organ transplantation, there is now a convergence in the transplantation community that pigs are the most desirable donor source for xenotransplantation. The reproductive characteristics and numbers of pigs allow for efficient breeding of their inbred lines, but the subsequent discovery in pigs that endogenous retroviruses (PERVs) can infect human cells in isolation has raised fears. Similar scenarios may occur in other animals unknown to humans, and xenotransplantation research moves forward in a comparison of benefits and risks. In conclusion, xenotransplantation is flourishing as a new technology that is an effective means of addressing the shortage of organ sources and alleviating the conflict between supply and demand. In particular, it can be used as a transitional means to buy more time for patients to wait for a suitable organ. Thus, patients’ lives can be extended. Bioethics regarding xenotransplantation has become an important issue of current interest to medical, philosophical, biological, sociological, religious communities, legislators, policy makers and the public. Although there are still many ethical issues that remain unresolved. But one day, with the renewal of the concept, the improvement of the quality of medical ethics of all people and the establishment and perfection of relevant laws and regulations and social security system, allogeneic organ transplantation will definitely release its due glory and will no longer be a distant dream.