Researchers trying to learn what killed the first person to receive a heart transplant from a pig have discovered the organ harbored an animal virus but cannot yet say if it played any role in the man’s death. A Maryland man, 57-year-old David Bennett Sr., died in March, two months after the groundbreaking experimental transplant. University of Maryland doctors said Thursday they found an unwelcome surprise — viral DNA inside the pig heart. They did not find signs that this bug, called porcine cytomegalovirus, was causing an active infection. Also read: US man who got 1st pig heart transplant dies after 2 months But a major worry about animal-to-human transplants is the risk that it could introduce new kinds of infections to people. Because some viruses are “latent,” meaning they lurk without causing disease, “it could be a hitchhiker,” Dr. Bartley Griffith, the surgeon who performed Bennett’s transplant, told The Associated Press. Still, development is under way of more sophisticated tests to “make sure that we don’t miss these kinds of viruses,” added Dr. Muhammad Mohiuddin, scientific director of the university’s xenotransplant program. The animal virus was first reported by MIT Technology Review, citing a scientific presentation Griffith gave to the American Society of Transplantation last month. For decades, doctors have tried using animal organs to save human lives without success. Bennett, who was dying and ineligible for a human heart transplant, underwent the last-ditch operation using a heart from a pig genetically modified to lower the risk that his immune system would rapidly reject such a foreign organ. The Maryland team said the donor pig was healthy, had passed testing required by the Food and Drug Administration to check for infections, and was raised in a facility designed to prevent animals from spreading infections. Revivicor, the company that provided the animal, declined to comment. Griffith said his patient, while very ill, had been recovering fairly well from the transplant when one morning he woke up worse, with symptoms similar to an infection. Doctors ran numerous tests to try to understand the cause, and gave Bennett a variety of antibiotics, antiviral medication and an immune-boosting treatment. But the pig heart became swollen, filled with fluid and eventually quit functioning. Also read:In 1st, US surgeons transplant pig heart into human patient “What was the virus doing, if anything, that might have caused the swelling in his heart?” Griffith asked. “Honestly we don’t know.” The reaction also didn’t appear to be a typical organ rejection, he said, noting the investigation still is underway. Meanwhile doctors at other medical centers around the country have been experimenting with animal organs in donated human bodies and are anxious to attempt formal studies in living patients soon. It’s not clear how the pig virus will affect those plans.

At first the pig heart was functioning, and the Maryland hospital issued periodic updates that Bennett seemed to be slowly recovering. Last month, the hospital released video of him watching the Super Bowl from his hospital bed while working with his physical therapist. Bennett survived significantly longer with the gene-edited pig heart than one of the last milestones in xenotransplantation -- when Baby Fae, a dying California infant, lived 21 days with a baboon’s heart in 1984. “We are devastated by the loss of Mr. Bennett. He proved to be a brave and noble patient who fought all the way to the end,” Dr. Bartley Griffith, who performed the surgery at the Baltimore hospital, said in a statement. Other transplant experts praised the Maryland team’s landmark research and said Bennett’s death shouldn’t slow the push to figure out how to use animal organs to save human lives. “This was a first step into uncharted territory,” said Dr. Robert Montgomery of NYU Langone Health, a transplant surgeon who received his own heart transplant. “A tremendous amount of information” will contribute to the next steps as teams at several transplant centers plan the first clinical trials. Also read: Successful transplant of pig's heart into a human body for the first time “It was an incredible feat that he was kept alive for two months and was able to enjoy his family,” Montgomery added. The need for another source of organs is huge. More than 41,000 transplants were performed in the U.S. last year, a record -- including about 3,800 heart transplants. But more than 106,000 people remain on the national waiting list, thousands die every year before getting an organ and thousands more never even get added to the list, considered too much of a long shot. The Food and Drug Administration had allowed the dramatic Maryland experiment under “compassionate use” rules for emergency situations. Bennett’s doctors said he had heart failure and an irregular heartbeat, plus a history of not complying with medical instructions. He was deemed ineligible for a human heart transplant that requires strict use of immune-suppressing medicines, or the remaining alternative, an implanted heart pump. Organ rejection, infections and other complications are risks for any transplant recipient. Experts hope the Maryland team quickly publishes in a medical journal exactly how Bennett’s body responded to the pig heart. Also read: In 1st, US surgeons transplant pig heart into human patient From Bennett’s experience, “we have gained invaluable insights learning that the genetically modified pig heart can function well within the human body while the immune system is adequately suppressed,” said Dr. Muhammad Mohiuddin, scientific director of the Maryland university’s animal-to-human transplant program. One next question is what evidence, from Bennett’s experience and some other recent experiments with gene-edited pig organs, may persuade the FDA to allow a clinical trial — possibly with an organ such as a kidney that isn’t immediately fatal if it fails.  Twice last fall, Montgomery’s team at NYU got permission from the families of deceased individuals to temporarily attach a gene-edited pig kidney to blood vessels outside the body and watch them work before ending life support. And surgeons at the University of Alabama at Birmingham went a step further, transplanting a pair of gene-edited pig kidneys into a brain-dead man in a step-by-step rehearsal for an operation they hope to try in living patients possibly later this year. Patients may see Bennett’s death as suggesting a short life-expectancy from xenotransplantation, but the experience of one desperately ill person cannot predict how well this procedure ultimately will work, said ethics expert Karen Maschke of The Hastings Center. That will require careful studies of multiple patients with similar medical histories. Transplant centers should start educating their patients now about what to expect as this science unfolds, said Maschke, who with funding from the National Institutes of Health is developing ethics and policy recommendations on who should be allowed in the first studies of pig kidneys and what they need to know before volunteering. Pigs have long been used in human medicine, including pig skin grafts and implantation of pig heart valves. But transplanting entire organs is much more complex than using highly processed tissue. The gene-edited pigs used in these experiments were provided by Revivicor, a subsidiary of United Therapeutics, one of several biotech companies in the running to develop suitable pig organs for potential human transplant.

In a medical first, doctors transplanted a pig heart into a patient in a last-ditch effort to save his life and a Maryland hospital said Monday that he's doing well three days after the highly experimental surgery. While it’s too soon to know if the operation really will work, it marks a step in the decades-long quest to one day use animal organs for life-saving transplants. Doctors at the University of Maryland Medical Center say the transplant showed that a heart from a genetically modified animal can function in the human body without immediate rejection. The patient, David Bennett, a 57-year-old Maryland handyman, knew there was no guarantee the experiment would work but he was dying, ineligible for a human heart transplant and had no other option, his son told The Associated Press. Also read: Chinese doctors complete lung transplant for COVID-19 patient “It was either die or do this transplant. I want to live. I know it’s a shot in the dark, but it’s my last choice,” Bennett said a day before the surgery, according to a statement provided by the University of Maryland School of Medicine. On Monday, Bennett was breathing on his own while still connected to a heart-lung machine to help his new heart. The next few weeks will be critical as Bennett recovers from the surgery and doctors carefully monitor how his heart is faring. There’s a huge shortage of human organs donated for transplant, driving scientists to try to figure out how to use animal organs instead. Last year, there were just over 3,800 heart transplants in the U.S., a record number, according to the United Network for Organ Sharing, which oversees the nation’s transplant system. "If this works, there will be an endless supply of these organs for patients who are suffering,” said Dr. Muhammad Mohiuddin, scientific director of the Maryland university's animal-to-human transplant program. But prior attempts at such transplants — or xenotransplantation — have failed, largely because patients’ bodies rapidly rejected the animal organ. Notably, in 1984, Baby Fae, a dying infant, lived 21 days with a baboon heart. Also read: In US 1st, baby is born from dead donor's transplanted womb The difference this time: The Maryland surgeons used a heart from a pig that had undergone gene-editing to remove a sugar in its cells that’s responsible for that hyper-fast organ rejection. Several biotech companies are developing pig organs for human transplant; the one used for Friday's operation came from Revivicor, a subsidiary of United Therapeutics. “I think you can characterize it as a watershed event,” Dr. David Klassen, UNOS’ chief medical officer, said of the Maryland transplant. Still, Klassen cautioned that it’s only a first tentative step into exploring whether this time around, xenotransplantation might finally work. The Food and Drug Administration, which oversees such experiments, allowed the surgery under what’s called a “compassionate use” emergency authorization, available when a patient with a life-threatening condition has no other options. It will be crucial to share the data gathered from this transplant before extending it to more patients, said Karen Maschke, a research scholar at the Hastings Center, who is helping develop ethics and policy recommendations for the first clinical trials under a grant from the National Institutes of Health. “Rushing into animal-to-human transplants without this information would not be advisable,” Maschke said. Over the years, scientists have turned from primates to pigs, tinkering with their genes. Just last September, researchers in New York performed an experiment suggesting these kinds of pigs might offer promise for animal-to-human transplants. Doctors temporarily attached a pig’s kidney to a deceased human body and watched it begin to work. The Maryland transplant takes their experiment to the next level, said Dr. Robert Montgomery, who led that work at NYU Langone Health. “This is a truly remarkable breakthrough," he said in a statement. "As a heart transplant recipient, myself with a genetic heart disorder, I am thrilled by this news and the hope it gives to my family and other patients who will eventually be saved by this breakthrough.” The surgery last Friday took seven hours at the Baltimore hospital. Dr. Bartley Griffith, who performed the surgery, said the patient’s condition — heart failure and an irregular heartbeat — made him ineligible for a human heart transplant or a heart pump. Griffith had transplanted pig hearts into about 50 baboons over five years, before offering the option to Bennett. “We’re learning a lot every day with this gentleman,” Griffith said. “And so far, we’re happy with our decision to move forward. And he is as well: Big smile on his face today.” Pig heart valves also have been used successfully for decades in humans, and Bennett’s son said his father had received one about a decade ago. As for the heart transplant, “He realizes the magnitude of what was done and he really realizes the importance of it,” David Bennett Jr. said. “He could not live, or he could last a day, or he could last a couple of days. I mean, we’re in the unknown at this point.”