First-ever transplant of animal lung in a human works for nine days

A 39-year-old man in a Chinese hospital, who was declared brain-dead, has become the first person in the world to receive a lung transplant from an animal of another species. The organ, from a genetically modified pig designed to prevent rejection, functioned for nine days until the patient’s family requested the experiment be ended.

Scientists at Guangzhou Medical University claim that the procedure “demonstrates the feasibility” of this treatment, while acknowledging that “significant challenges” remain. The Chinese company Clonorgan Biotechnology was responsible for humanizing the pig lung to allow its acceptance by the human body. The company’s stated goal is to become “the organ factory of the future.”

The first efforts to carry out animal-to-human transplants — known as xenotransplantation — were marked by setbacks. The first attempt occurred in 1906 when French surgeon Mathieu Jaboulay implanted a pig kidney into the elbow of a 48-year-old woman, without success. In 1909, German surgeon Ernst Unger transplanted a monkey kidney into the thigh of a 21-year-old patient, who died on the second day.

After several desperate trials, research was abandoned for decades. The advent of the revolutionary CRISPR technique in 2012 — a sort of molecular scissors that allow easy DNA editing — ushered in a new era. In January 2022, American David Bennett became the first human to live with a pig heart beating in his chest, but he died two months later from an unexpected stowaway: a porcine cytomegalovirus.

Clonorgan Biotechnology used CRISPR to genetically modify a Bama Xiang pig, a breed native to a mountainous region in southern China. The company inserted three human genes and silenced three pig genes to prevent organ rejection. The donor pig, a 70-kilogram male, was raised in total isolation under strict biosecurity conditions to prevent contact with pathogens. The results of the operation, performed on May 15, 2024, were published Monday in the specialized journal Nature Medicine.

The researchers behind the experiment acknowledge its limitations. The man in Guangzhou had been experiencing a severe cerebral hemorrhage for 16 days but still retained his right lung, which may have influenced the functionality of his new left lung from the pig donor.

One of the lead investigators, surgeon Xin Xu, explains the challenges: “Our goal is to create a rigorous scientific path toward safe and long-lasting lung xenotransplantation, but today we are not clinically prepared,” he tells EL PAÍS. “We are planning further experiments in brain-dead people. Many key issues remain to be addressed, such as testing double-lung transplantation, evaluating pig organs with more specific genetic editing, and refining immunosuppressive regimens [the combinations of drugs given to a patient to prevent their own immune system from attacking the transplanted organ].” Among the study’s signatories are Dengke Pan, founder of Clonorgan Biotechnology, and surgeon Jianxing He, a leading figure in lung transplantation in China.

David Bennett’s transplant in 2022, using a genetically modified pig heart from the U.S. company Revivicor, ushered in a period of hope. Bennett himself joked when offered a pig organ: “Will I go oink, oink?” he asked his surgeon at the University of Maryland Medical Center.

The second recipient of a pig heart, Lawrence Faucette from the U.S., died six weeks later due to organ rejection.

Also in the United States, Rick Slayman, the first living patient with a genetically modified pig kidney transplant, died two months after the procedure, in May 2024, but his doctors attributed his death to a heart problem.

Two months earlier, surgeons at a military hospital in Xi’an, China, transplanted a transgenic pig liver into a 50-year-old brain-dead patient — the liver also came from Clonorgan Biotechnology, based in Chengdu.

The lung is the most recent organ added to this list because it is one of the hardest to transplant, as it is constantly exposed to air and pathogens. In January 1997, Indian surgeon Dhani Ram Baruah claimed to have implanted a pig heart and two lungs into a 32-year-old man, Purna Saikia, who died a week later. The surgeon was arrested and charged with homicide, and there is skepticism about the actual transplant.

The journal of the United States Society of Thoracic Surgeons does not include that alleged lung transplant in its history of xenotransplantation. Thus, the 39-year-old man in the Guangzhou hospital would be the first person to have an animal lung in his chest, albeit in a brain-dead state.

Spanish surgeon Pablo Ramírez, from Virgen de la Arrixaca Hospital in Murcia, has requested authorization to conduct a trial in which his team would transplant pig livers, genetically modified at the Technical University of Munich in Germany, into three patients with acute liver failure, for a few days until human donor livers became available. Ramírez praised the new study from the Chinese team. “The scientific significance of this publication is that it demonstrates, for the first time in the history of medicine, that a polytransgenic pig lung, with human genes, can function adequately for at least nine days in a person,” he says.

Ramírez highlights that the pig organ did not trigger hyperacute rejection — the most severe form of human immune response to an organ from another species — in the Guangzhou patient. However, the brain-dead patient did experience a different type of antibody-mediated rejection on the third day, which the Chinese doctors controlled with immunosuppressive drugs.

For Ramírez, the “impeccable design” of the Chinese experiment has illuminated the mechanisms of rejection and will allow new strategies for genetic modifications in donor pigs. On its website, Clonorgan Biotechnology emphasizes its goal: “To become the global leader in the medical-use pig donor industry.” In Spain alone, roughly 800 people are on the waiting list for a lung transplant.

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