With the patient doing well after three days, UMMC officials said that the genetically modified animal heart is functioning like a human heart without immediate rejection by the body. Doctors are carefully monitoring the patient — David Bennett of Maryland — to determine whether the transplant provides lifesaving benefits. “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,” said Bennett in the university’s press release the day before the surgery. He had been hospitalized and bedridden for the previous few months. “I look forward to getting out of bed after I recover.”
FDA’s Authorization Paved the Way for Surgery
The surgery was allowed through an emergency authorization granted by the U.S. Food and Drug Administration (FDA) through its expanded compassionate use provision. The policy permits an experimental medical product (in this case the genetically modified pig’s heart) to be used when it is the only option available for a patient faced with a serious or life-threatening medical condition. Public health officials see promise in this type of animal-to-human transplant as a means to alleviate a shortage of human organs. More than 106,000 men, women, and children are currently on the national transplant waiting list, according to OrganDonor.gov, and the FDA says that currently 10 patients die each day in the United States while on the waiting list to receive a lifesaving vital organ transplant. “This was a breakthrough surgery and brings us one step closer to solving the organ shortage crisis,” said Bartley P. Griffith, MD, who surgically transplanted the pig heart into the patient. (Dr. Griffith is a professor of transplant surgery at the University of Maryland School of Medicine and the director of the cardiac transplant program at UMMC.) “There are simply not enough donor human hearts available to meet the long list of potential recipients. We are proceeding cautiously, but we are also optimistic that this first-in-the-world surgery will provide an important new option for patients in the future.” Considered one of the world’s foremost experts on transplanting animal organs (known as “xenotransplantation”), Muhammad Mohiuddin, MD, a professor of surgery at University of Maryland School of Medicine, told U.S. News & World Report, “If this works, there will be an endless supply of these organs for patients who are suffering.”
Rocky Road for Animal-to-Human Transplants
The road to this successful xenotransplantation has been long. First tried in the 1980s, animal-to-human organ transplants were largely abandoned after the famous case of Stephanie Fae Beauclair (known as Baby Fae) at Loma Linda University in California. The infant, born with a fatal heart condition, received a baboon heart transplant and died within a month of the procedure because her immune system rejected the foreign heart. Pig heart valves, however, have been used successfully to replace valves in humans for many years because of physiological similarities between pigs and humans. Bennett did not qualify to be on the transplant list and was ineligible for an artificial heart pump due to his arrhythmia. Fully aware of the risks, Bennett chose the option because he had been admitted to the hospital more than six weeks earlier with life-threatening arrhythmia and was connected to a heart-lung bypass machine, called extracorporeal membrane oxygenation (ECMO), to remain alive.
Immune Response Risk in Transplantation Surgery
Every xenotransplantation runs the risk of triggering a dangerous immune response. This operation differed from previous failed attempts at xenotransplantation because genes in the pig donor had been altered to inhibit organ rejection and improve immune response. Three genes — responsible for rapid antibody-mediated rejection of pig organs by humans — were “knocked out” in the donor pig. Six human genes responsible for immune acceptance of the pig heart were inserted into the genome. Lastly, one additional gene in the pig was knocked out to prevent excessive growth of the pig heart tissue, which totaled 10 unique gene edits made in the donor pig. The surgery team also used a new drug along with conventional anti-rejection drugs, which are designed to suppress the immune system and prevent the body from rejecting the foreign organ. In October of last year, another xenotransplantation showed promise when a pig kidney was attached to a brain-dead woman and maintained function for three days. “We appreciate the tremendous courage of this live recipient, who has made an extraordinary decision to participate in this groundbreaking procedure to not only potentially extend his own life, but also for the future benefit of others,” said Mohan Suntha, MD, the president and CEO of the University of Maryland Medical System, in a the press release.
