Scientists perform first pig-to-human lung transplant

NEW YORK: Scientists have dreamed for centuries about using animal organs to treat ailing humans. In recent years, those efforts have begun to bear fruit: Researchers have begun transplanting the hearts and kidneys of genetically modified pigs into patients, with varying degrees of success.

But lungs are notoriously difficult to transplant, even from human to human, and mortality rates are high. Now, in the first procedure of its kind, Chinese scientists on Monday reported transplanting a lung from a pig into a brain-dead man.

The organ sustained damage after it was transplanted but functioned to some degree, scientists at Guangzhou Medical University reported in the journal Nature Medicine. The organ was removed after nine days.

American scientists called the procedure exciting but urged caution.

“It’s very promising and a great first step, but there is a lot more work to do to make this feasible,” said Dr Stephanie Chang, an associate professor in cardiothoracic surgery at New York University Grossman School of Medicine and surgical director for the lung transplant programme.

“If there is a way to actually source organs from animals and have them work in genetically modified ways, that would be very exciting,” she said.

While dialysis can help people with kidney failure, “there’s not much that can replace your lungs,” Chang added.

In the United States alone, millions suffer from severe, life-threatening lung disease, including chronic conditions caused by COVID. Yet there is an extreme shortage of human lungs available for transplant. Many donor organs, damaged by a lifetime of environmental exposure, are simply not in good enough condition to transplant.

The Chinese scientists transplanted the left lung of a pig that had undergone six gene edits into a brain-dead 39-year-old man. Because the procedure left his functioning right lung in place, the experiment did not prove that the transplanted lung could sustain life on its own, critics noted.

“It’s impressive, but it doesn’t answer the question: Is that lung working?” said Dr. Richard N Pierson, a professor of surgery at Harvard Medical School and the Massachusetts General Research Institute, who has done extensive research on pig heart transplants.

The research team could have blocked off blood flow to the right lung in order to assess how well the transplant was working, he said, but they did not. “They’ve shown a pig lung can be sewn into a human being and shown what happens,” he said. “But an opportunity was missed in this experiment.”

The Chinese authors of the report did not respond to email queries for more information.

The pig’s lung also suffered damage within 24 hours of the transplant. Signs of antibody-mediated rejection, which occurs when the body forms antibodies and attacks the organ and is the most common cause of transplant failure, were observed at three and six days after transplantation. Fluid buildup was also discovered in the lung.

Since lungs come into contact with the environment with every breath and are constantly being exposed to external threats, like allergens, pollutants and viruses, they are rich in immune cells.

The immune responses in these organs are thus more aggressive than those seen in other solid organs, like the kidney, and transplanted lungs are more likely to fail.

“If you put all the organs on a spectrum, the lung will always be the hardest to do,” said Dr Leonardo Riella of Massachusetts General Hospital, who performed the first successful transplant of a kidney from a gene-edited pig into a living human.

In human-to-human transplants, “a normal kidney may last 12 to 14 years, while a lung may last five to seven years,” he said.

Research teams around the world have been increasing the number of experiments with organs from genetically modified pigs bred by different companies, with various sets of gene edits.

In March, a team of Chinese scientists reported that they had transplanted a genetically altered pig’s liver into a brain-dead person, where it functioned for 10 days, producing bile and porcine albumin and maintaining stable blood flow without signs of rejection.

The US company eGenesis is also studying the transplantation of pig livers in addition to other organs. In April, the company received authorisation from the Food and Drug Administration to start clinical trials using pig livers to treat patients with a condition called acute-on-chronic liver failure. The treatment involves circulating the patients’ blood outside the body through the animal’s liver.

Much of the focus of such clinical research has been on kidneys, since more than 5,00,000 Americans suffer from kidney failure and require dialysis, including about 100,000 who are on waiting lists for human kidneys. There is an acute shortage of donated organs, with fewer than 25,000 transplants completed in 2023. Many patients die while they wait.

In February, the FDA also gave the go-ahead to United Therapeutics Corp to start a clinical trial transplanting kidneys from genetically engineered pigs into patients with kidney failure.

One New Hampshire man who received a kidney from a genetically altered pig produced by eGenesis has been living with the organ since January. He is the longest survivor with a pig’s kidney to date.

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