The infamous event that is the pig heart transplant of January 2022 was viewed as both an inhumane abomination and a scientific revelation. Integrating gene modification technology, the University of Maryland School of Medicine (UMSOM) proceeded in January 2022 with the xenotransplantation of a pig’s heart into 57-year-old patient David Bennett. Dubbed an “early success” due to a record-breaking survival of two months, the surgery had lacked precursory signs of rejection until mere days before his death. Nevertheless, that very transplant was a monumental development that solidified the progress in xenotransplantation and expedited similar procedures.
According to the Center for Disease Control and Prevention, xenotransplantation is defined as “the use of live animal cells, tissues and organs in the treatment or mitigation of human disease.” Alternatively, there is the more widely-known surgery, as reported by Nature, of allotransplantation the “transplantation of an organ or tissue from one individual to another of the same species with a different genotype. The transplant is called an allograft.”
Recognizing the increasing disparity between the demand for organs and the viable supply, the major dependency on allografts has evolved into similar but distinctly unique methods. Whether it be the genetic modification of human organs in of itself, developing techniques to revive previously damaged organ donations, and more–the most plaguing method would be xenotransplantation.
While the United States has recently acquired praise for carrying out an experimental xenotransplantation on a willing subject, allowing for the collection of essential new data, there have been other countries with equally impactful developments.
Among those dominating the field of transplantation is China.
The Fatal Beginning
Amidst a tense political climate, China is currently confronting scrutiny over its barbaric detention of Uyghurs and rampant violations of human rights. On the other hand, the nation has received minimal acknowledgment of its medical advances, both historically and in the present.
The concept of xenotransplantation has been established to extend beyond the physical implantation of organs. Its origins began with blood transfusion. The first recorded instance of animal-to-human blood transfusion in 1667 was by Jean-Baptiste Denis, with a sheep being used as the blood source for both a young boy and woman in labor. This continued with skin grafts in the 17th-18th centuries and a plethora of failed ventures with kidney transplants in the 20th century. Since these endeavors tragically each concluded in fatalities within mere days, the majority from thrombosis (ie. blood clots), all attempts came to a cease for 40 years after 1923.
The true revolution for xenotransplantation occurred in November 1963 when Keith Reemtsma transplanted monkey kidneys to 13 different patients with the utilization of immunosuppressants–allowing for the first long-term success of up to nine months. Following attempts did not all equate to comparable success, but the length of survival had irrefutably increased. Other countries, such as Italy, South Africa, Germany, and, expectedly, China, became involved through varying focuses and experimentations with xenotransplantation as an alternative to allotransplantation. The evolution of medical interventions was further reinforced through the integration of genetic engineering, as the organs of the animals could therefore be modified to better suit the patient’s genetic composition. One of the grand advances due to the contributions of genetic modification was, predictably, the January 2022 pig transplant. After its tragic conclusion, the Director of the Cardiac Xenotransplantation Program at the UMSOM, Muhammad M. Mohiuddin, stated in response to Bennett’s death, "We are very encouraged by this finding, and it suggests that the genetically modified pig heart and the experimental drug we used to prevent rejection worked effectively in tandem to demonstrate that xenotransplants can potentially save future lives."
China’s Pig-Sized Debacle
While Bennett’s surgery had been authorized by the Food and Drug Administration (FDA), the United States continues to confront complications as it conforms with the FDA’s 1999 ban on xenotransplantation. China, on the other hand, has accelerated its xenotransplantation-focused programs in order to address its critically low supply of organ donations. As reported by the South China Morning Post, there had only been around 10,000 organ donations from 2010 to 2016 in China. Moreover, the devastating shortage of organs had been further exacerbated in 2015 by the World Medical Association (WMA) who successfully required China to comply with their demands to renounce the continuation of nonconsensual organ collection from executed prisoners, a practice that had composed the majority of organ “donations.”
Recent statistics indicate that voluntary efforts have elevated the number of registered organ donors in exponential amounts, with the Red Cross Society of China reporting around 1.54 million newly registered donors. Nevertheless, China continues to dedicate itself to advancing a dependency on genetically modified pigs for organ transplantation.
China’s experimentation on pigs is not exclusive to the country, but its relationship with the stout, pink mammal is unique. Their history is rooted in the successful production of the world’s fourth Green Fluorescent Protein transgenic pig by Dr. Zhonghua Liu–the first of its kind to be completed by transgenic somatic cell nuclear transfer. This historical moment foreshadowed China’s continuing research and discoveries regarding the usage of genetically modified pigs as a solution to transplant organs.
However, these pigs have been acknowledged as a tenuous source due to the vast number of piglet embryos involved in producing even a single, sufficiently viable pig. In 2018, China's reliance on pigs was exposed by the epidemic of African swine fever, which had eliminated the majority of the pig population and temporarily halted clinical trials. This has also created doubts whether animal welfare is truly being adhered to as the breeding process for these pigs has been considerably suboptimal. Nevertheless, pigs have otherwise been viewed as the ideal organ donor towards advancing the technology, as their organ size, metabolism, and immune system are nearly identical to humans. Pigs have been recognized as the favorable source of neuronal cells, red blood cells, eye tissues, kidneys, pancreatic islets, livers, lungs, and hearts. The compatibility of the organs to those of humans has reduced the rejection rate to virtually nonexistent, at least for relatively long periods. While China’s principles of animal protection can be questioned, the success of these operations following the shift to pigs is not.
Recognized as a leader amongst the nations in terms of advancements with xenotransplantation technology, many notable associations have acted towards establishing an effective regulatory framework. The PHG Foundation reflects in a briefing that the 2018 Changsha Communiqué had formulated principles in accordance with the World Health Organization (WHO) and International Xenotransplantation Association (IXA), along with following the previously installed FDA guidelines.
China’s Current Status with Xenotransplantation
Addressing the ethical issues plaguing China, the China Organ Transplantation Development Foundation in January 2022 reached a formal consensus during a symposium. It established the future perimeters of clinical trials dedicated to xenotransplantation, as advised by the Bureau of Medical Administration of the National Health Commission. Due to the questioning of China’s ability to abide by these mandates, there was also the grand attendance of people from the China Organ Transplant Response System Scientific Committee, medical workers, university professors, and more.
However, there has been recent debate regarding whether China truly has remained within regulations, as there have been allegations that the nation has been acquiring organs through brutal force. According to the Human Rights Commission House Committee on Foreign Affairs, the allegations have encompassed wrongdoing against marginalized minorities, such as Falun Gong practitioners and Uyghurs, as recent medical testing points towards the potential use of prisoners for organ removal. As China has been frequently questioned in the past by the WHO, IXA, FDA, and other organizations on its ability to abide with the legislation implemented in previous conferences, there leaves room to doubt whether future procedures of xenotransplantation may cross the borders of morally sound ethics.
Recognizing China’s modernization of xenotransplantation on the international platform, the PHG Foundation reflects the concerns towards China, saying “further evidence from preclinical studies in primate models should be presented to support the efficacy and safety of clinical trial of xenotransplantation for human subjects in China.”
Opportunities to criticize the Asian country are not to falter, even with the newfound utilization of CRISPR to formulate allogeneic cell therapies with donor cells, which has lowered costs and time in providing blood cancer treatment. Recent events like the worldwide implementation of artificial intelligence have certainly left the possibility of further progression in the sphere of xenotransplantation, especially with China rising as a global leader of artificial intelligence.
Regarding the professional opinions of Chinese medical workers, the National Library of Medicine has their quote that “given the recent influx of world-renowned scientists in xenotransplantation to China, our country will definitely become one of the major centers of xenotransplantation research and development in the world.”
While the ethics of China’s organ harvesting are not guaranteed, the republic continues to advance on its agenda to develop genetically modified pig organs–both for the world-wide progression of organ transplantation and to enforce humane practices within the nation.
Cover picture of pigs flying in neon signs to signify Chinese New Year. By Marcellin Bric via Unsplash.
