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A 58-year-old man has become the second person ever to receive a heart transplant from a genetically modified pig. The patient, Lawrence Faucette, was facing near death from heart failure and wasn’t eligible for a traditional transplant with a human organ.
So surgeons at the University of Maryland Medical Center gave him the option of receiving a highly experimental procedure that has only been tried once before. Faucette agreed, and after undergoing the surgery on September 20, his heart is reportedly functioning well without any assistance from supportive devices. “At least now I have hope, and I have a chance,” Faucette said in a university statement before the procedure. For decades, the Maryland group and others have been exploring xenotransplantation, or transplanting animal organs into people, as a way to ease the donor organ shortage. In the United States alone, more than 104,000 people are waiting for a transplant, and 17 of them die each day. More than 3,000 are specifically in need of a heart, according to the Organ Procurement and Transplantation Network.
Researchers have turned to pigs as potential donors because their organs are similar to humans’ in size. But the procedure has many uncertainties. Pig organs aren’t naturally compatible with human bodies and are likely to trigger a fatal immune response. To make their organs more suitable for people, scientists have been tinkering with donor pigs’ genes. The pig used for Faucette’s transplant had a total of 10 genetic edits. Three of the genes responsible for immune rejection were knocked out, while a fourth was deleted to prevent excessive growth of the pig heart tissue. Six human genes responsible for immune acceptance were added.
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The first person to receive a genetically engineered pig heart, David Bennett, did so in January 2022. The heart had the same gene edits as Faucette’s, and the transplant was also performed by the Maryland team. It worked—initially. For seven weeks, Bennett showed strong cardiac function with no obvious signs of acute rejection, a complication that arises if the person’s immune system treats the new organ as foreign and attacks it.
Yet he died two months later of sudden heart failure. The Maryland researchers have been studying his case in hopes of improving the odds of survival for subsequent patients. “I think we have learned pretty much what we can learn from David’s tissues and his clinical course,” Bartley Griffith, the surgeon who conducted both transplants, told WIRED in December. “We believe we can avoid some of the pitfalls that we had with David because he did so well for so very long.” (When reached via email on Monday, the Maryland team declined an interview about Faucett’s case, saying they are still “early in the process” with the transplant.)
In June, that team published an analysis of what led to Bennett’s heart failure. They concluded that several factors were likely at play, including his poor health before the transplant. The Maryland researchers also detected traces of a latent pig virus, called porcine cytomegalovirus, or PCMV, in Bennett’s blood. The virus can cause inflammation and cell damage. There’s no evidence that this virus spread beyond the heart, but it may have contributed to the failure of the transplant.
“We know from primate experiments when porcine cytomegalovirus gets activated in xenografts in baboons that bad things happen to the baboon and bad things happen to the xenograft,” says Richard Pierson, who is the scientific director of the Center for Transplantation Sciences at Massachusetts General Hospital and wasn’t involved in the heart transplants.
With any organ transplant, doctors are trying to balance how to prevent infections while tamping down the immune system. Without immunosuppressive drugs, the transplant organ will be rejected. But giving patients too much of these drugs makes them susceptible to infections.
That’s what researchers think happened in Bennett’s case. To treat the CMV infection, doctors gave Bennett a therapy called intravenous immunoglobulin, which is meant for patients with compromised immune systems, including transplant patients. A concentrated pool of antibodies from thousands of human donors, the treatment likely contained natural antibodies that attacked the pig organ and damaged muscle cells.
The Maryland doctors are taking different steps to prevent Faucette’s new heart from being rejected. For one, they told WIRED in December that they had developed a new, more sensitive test to detect very small amounts of pig virus DNA. Before the latest transplant, they tested the donor pig regularly for CMV and other porcine viruses, as well as bacteria and parasites. “At the present time, we have no reason to believe this donor pig is infected with porcine PCMV, which is the virus that was identified in our first xenotransplant recipient,” a university spokesperson told WIRED in an email.
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Doctors are treating Faucette with traditional immunosuppressive drugs, along with an investigational antibody therapy called tegoprubart, developed by California biotech company Eledon Pharmaceuticals. The drug works by blocking CD154, a protein involved in immune rejection, and is given via IV every three weeks. As with other immunosuppressive drugs, Faucette must receive it for the rest of his life to prevent his new heart from being rejected. “When you block this receptor, it’s very, very effective to prevent transplant rejection,” says Steve Perrin, Eledon’s president and chief scientific officer.
When the Maryland surgeons performed Bennett’s transplant in January 2022, they didn’t have access to Eledon’s drug because it had not yet been tested in humans. Now, more than 100 people have received the drug in early clinical trials. Tegoprubart has also been tested in non-human primates and been shown to increase the life of transplanted pig organs in those animals.
The next few weeks will be crucial to determine whether the transplanted pig heart will continue to function normally. “I’m hopeful that this will be the correct regimen for the patient and that he will be able to live a long life with the xenograft,” says Jayme Locke, an abdominal transplant surgeon at the University of Alabama at Birmingham who wasn’t involved in the heart cases. In August, Locke’s team published a study showing that a genetically modified pig kidney functioned normally in a brain-dead patient for a week.
In a separate xenotransplant experiment, a team at NYU Langone announced earlier this month that it kept a pig kidney working for two months in a brain-dead person.
The US Food and Drug Administration granted emergency approval for Faucette’s surgery earlier this month through its “compassionate use” pathway. This process, which was also used for Bennett’s transplant, is applied when an unapproved medical product—in this case, the genetically modified pig heart—is the only option for a patient with a serious or life-threatening condition.
Pierson thinks these individual cases of pig-to-human transplants will help generate evidence needed for more formal clinical trials that will include multiple patients. He is optimistic that a pig heart will function longer in this second patient. “Full stop,” he says. “It may not work every time we do it, but we’re going to learn a lot from these one-offs.”
