Organ transplantation, known as xenotransplantation, from pigs to humans, such as organs like the heart and kidneys, is being carried out one after another. Pig organs have similar size and shape to humans and have been noted as an alternative to solve the long-standing problem of organ shortages for transplantation since several decades ago. The issue, however, is the immune rejection response. There have often been cases in which the human body recognizes pig organs as foreign substances and attacks them, preventing proper functioning.
Scientists are finally finding answers. The international journal Science featured a special article titled 'The Organ Farm' on the 29th of last month, introducing individuals who received genetically edited pig kidneys that have eliminated immune rejection, thereby saving their lives. These patients had already suffered significant kidney damage, and transplantation was their only hope, but they had no alternative due to the inability to find compatible organs.
According to Science, approximately 37 million people in the United States suffer from chronic kidney disease, with about 100,000 awaiting kidney transplants. However, due to a severe shortage of donor organs, only 25,000 kidney transplants were performed throughout 2023. The National Kidney Foundation estimates that about 12 people die each day waiting for a kidney transplant.
◇Pig kidneys record functionality for 4 months in human body
Scientists have proposed xenotransplantation as an alternative in a situation where the number of candidates waiting for organ transplantations has been overwhelming. Norman Shumway, a pioneer in heart transplantation and a professor at Stanford University School of Medicine, stated in Science 20 years ago, "With advancements in gene editing, cloning, and immune suppression technologies, along with active support from investors, the realization of xenotransplantation is not far off." He successfully performed the first heart transplant in the U.S. in 1968.
Professor Shumway's prediction is becoming a reality. Recently, research on transplanting pig organs to humans has become noticeably active. One of the most notable corporations is United Therapeutics Corporation (UTC) in the U.S. UTC is developing a kidney called 'UKidney,' which can be transplanted into humans by modifying the genes of pigs raised in a sterile environment. The company edited 10 pig genes to humanize pig kidneys, adding 6 human genes and suppressing 4 pig genes.
In February of this year, UTC received approval from the U.S. Food and Drug Administration (FDA) to conduct clinical trials to transplant the genetically edited pig kidneys, which reduced immune rejection, into patients with kidney failure. This is the first clinical trial aimed at commercializing xenotransplantation in the U.S. The company plans to conduct initial trials with 6 patients who have undergone dialysis for at least 6 months and have no other complications, intending to expand the participants to 50 if successful.
Another U.S. biotechnology company, eGenesis, also received FDA approval last year to transplant genetically modified pig kidneys into kidney failure patients. In January, they performed a second pig kidney transplant on a man in his 60s. eGenesis is also conducting clinical trials to transplant pig livers into patients with liver failure. They are expected to apply for new clinical approvals to expand transplantation subjects within the year. The clinical trials by eGenesis also involve OrganOx from the U.K.
In China, clinical trials for xenotransplantation are also gaining momentum. ClonOrgan Biotechnology successfully transplanted pig kidneys into a woman in her 60s last March.
David Cooper, a professor at the Massachusetts General Hospital (MGH) of Harvard Medical School and an expert in xenotransplantation, stated, "Our goal is for patients who receive pig kidneys to live healthily for at least 6 months to over a year." The FDA acknowledges a transplant as successful if the kidney functions for 6 months post-operation.
Richard Slayman, a 62-year-old American who received the first genetically modified pig kidney transplant last March, died two months after the surgery. The surgery used a kidney from a pig genetically modified by eGenesis. The Massachusetts General Hospital, which performed the transplant, stated there were no indications that the patient died due to the kidney transplant.
So far, the longest record was set when the pig kidney transplanted into 53-year-old American Towana Rooney in November of last year functioned for just over 130 days. Rooney underwent the transplant surgery and was discharged from the hospital in February of this year, discontinuing dialysis. However, later on, an immune rejection occurred, and the transplanted pig kidney was removed. The patient subsequently resumed dialysis treatment and regained health.
◇Korea also accelerates research…"Clinical trial approval targeted for next year"
There is a high demand for xenotransplantation in Korea as the chronic shortage of transplant organs remains unresolved. In 2023, 2,906 people in the country died while awaiting organ transplants. Recently, the government has begun to intensify research on xenotransplantation.
The Ministry of Health and Welfare is conducting a national project worth 38 billion won, aiming to enter clinical trials for xenotransplantation within 5 years by 2023. The research scope includes major organs like kidneys, hearts, and livers, as well as cellular tissues like the pancreas, corneas, and skin. Currently, preclinical trials using primates are underway under the leadership of Professor Yoon Ik-jin of Konkuk University Hospital (president of the Korean Xenotransplantation Research Society).
The National Institute of Health Science and Technology (KIT) is conducting a project on 'Postoperative Care and Vital Monitoring of Non-Human Primate Recipients of Xenogeneic Solid Organ Transplantation.' Recently, a pig kidney developed by the domestic corporation Optipharm was transplanted into a monkey, setting a survival record of 221 days. They also set a survival record of 217 days after pig heart transplantation, exceeding the clinical standard of 180 days.
Domestic private corporations have also entered the field of xenotransplantation. Optipharm and GenNBio are representative corporations. Optipharm is developing genetically modified pigs, altering the genes of mini pigs whose organ sizes are similar to humans, such as hearts and pancreases, to minimize immune rejection. The company is working on developing 'genetically modified pigs with 10 gene edits' by removing 4 pig genes and inserting 6 human genes, making them the first in the country.
Kim Hyun-il, CEO of Optipharm, noted, "The monkeys used domestically are smaller than those from the U.S. which limits their survival periods, and there are various restrictions on conducting clinical research using deceased donor organs. However, we plan to submit an Investigational New Drug application for clinical trials for xenotransplantation, including pig pancreases, to the Ministry of Food and Drug Safety by next year."
GenNBio is led by former CEO Kim Sung-joo, who has served as the head of the organ transplantation center at Samsung Medical Center and the director of the Seoul Laboratory Animal Research Center, and initially garnered attention, but recently entered a rehabilitation process due to declining profitability. However, unable to secure a merger and acquisition (M&A) investor, they filed for a petition to cancel their rehabilitation process on the 5th.
◇"Research on deceased donor transplantation must be permitted like overseas"
Professor Yoon noted, "While technologies like gene editing and genetically modified pigs have already been developed, currently, there are high practical barriers for entering clinical trials for xenotransplantation, including fulfilling survival days and selecting clinical subjects."
Professor Yoon emphasized the need for research on transplanting xenogeneic organs into deceased donors, similar to practices in the U.S. and China. The idea is to first confirm the efficacy and safety on deceased donors before expanding to actual patients.
In fact, American medical personnel performed the first pig kidney transplant on a 57-year-old man who was declared brain dead due to a motorcycle accident in 2022. Just 23 minutes after the transplant surgery, the pig kidney began producing urine and functioned normally for three days.
Chinese scientists reported in the international journal Nature last March that a genetically modified pig liver functioned normally for 10 days after being transplanted into a brain-dead patient. The pig liver was transplanted into the human body and started secreting bile 2 hours later. Professor Yoon stated, "To proceed with xenogeneic organ transplantation for deceased donors, it's necessary to amend the law to recognize brain dead individuals as deceased through social discourse."
References
Science(2025), DOI: https://doi.org/10.1126/science.zlopfu3