The pig-to-human surgery in Maryland was given emergency approval on the New Year’s eve by the U.S. Food and Drug Administration (FDA) through a provision that allows experimental treatments to be used when there is no other option to save a patient’s life, reports Press Xpress
Doctors have transplanted the heart from a genetically modified pig into the chest of a man from Maryland of USA in a last-ditch effort to save his life. The first-of-its-kind surgery is being hailed as a major step forward in the decades-long effort to successfully transplant animal organs into humans.
The surgery, performed by a team at the University of Maryland Medicine in the United States, is among the first in the world to demonstrate the feasibility of a pig-to-human heart transplant, a field made possible by new gene editing tools.
The January 7 pig heart transplant comes right on the heels of surgeons in New York successfully attaching the kidney of a genetically engineered pig to a brain-dead person in October last year.
Dr Bartley Griffith, director of the cardiac transplant programme at the University of Maryland School of Medicine (UMSOM), surgically transplanted the pig heart into the patient. He was assisted by one of the world’s foremost experts on xenotransplantation, Dr Muhammad M. Mohiuddin, Professor of Surgery at UMSOM.
Revivicor, a regenerative medicine company provided the genetically-modified pig to the xenotransplantation laboratory at UMSOM. On the morning of the transplant surgery, the surgical team, led by Dr Griffith and Dr Mohiuddin, removed the pig’s heart and placed it in the XVIVO Heart Box, a device that keeps the heart preserved until surgery.
The doctors also used an experimental drug made by Kiniksa Pharmaceuticals along with conventional anti-rejection drugs, which are designed to suppress the immune system and prevent the body from rejecting the foreign organ.
“The anatomy was a little squirrelly, and we had a few moments of ‘uh-oh’ and had to do some clever plastic surgery to make everything fit,” Dr Griffith said. As the team removed the clamp restricting blood supply to the organ, “the heart fired right up,” and “the animal heart began to squeeze,” the doctor told The New York Times.
“This is the culmination of years of highly complicated research to hone this technique in animals with survival times that have reached beyond nine months. The FDA used our data and data on the experimental pig to authorize the transplant in an end-stage heart disease patient who had no other treatment options,” said Dr. Mohiuddin. “The successful procedure provided valuable information to help the medical community improve this potentially life-saving method in future patients.”
Two newer technologies — gene editing and cloning — have yielded genetically altered pig organs less likely to be rejected by humans. Three genes — responsible for an aggressive rejection response by human immunity response — were “inactivated” in the donor pig. Six human genes responsible for immune acceptance were inserted into the genome.
Finally, one additional gene in the pig was also inactivated to prevent excessive growth of the pig heart tissue. Pig hearts grow into adult human size in six months. There were 10 unique gene edits made in the donor pig in total.
“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, the patient, a day before the surgery was conducted. He had been hospitalized and bedridden for the past few months. “I look forward to getting out of bed after I recover,” Bennett added, stated the university’s press release.
“It creates the pulse; it creates the pressure; it is his heart,” said Dr Griffith. “It’s working, and it looks normal. We are thrilled, but we don’t know what tomorrow will bring us. This has never been done before,” reported The New York Times.
According to the United Network for Organ, that administers the only Organ Procurement and Transplantation Network in the United States Last year, some 41,354 Americans received a transplanted organ, more than half of them receiving kidneys.
About 1,10,000 Americans are currently waiting for an organ transplant, and more than 6,000 patients die each year before getting one, according to the US federal government’s organdonor.gov website.
“This was a breakthrough surgery and brings us one step closer to solving the organ shortage crisis. There are simply not enough donor human hearts available to meet the long list of potential recipients,” said Dr Griffith, who surgically transplanted the pig heart into the patient. “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.”
Cross-species transplantation offers the prospect of an unlimited supply of organs and cells for transplantation, thus resolving the critical shortage of human organs that currently prohibits a significant portion of patients on the waiting list from receiving transplants.
In the US, about 20 per cent of patients on the heart transplant waiting list die while waiting to receive a transplant or become too sick to be good candidates for the complex transplant procedure. It was informed that the UMSOM received a $15.7 million sponsored research grant to evaluate Revivicors’ genetically-modified pig hearts.
The U.S. Food and Drug Administration granted emergency authorization for the surgery on New Year’s Eve through its expanded access (compassionate use) provision. It is used when an experimental medical product, in this case the genetically-modified pig’s heart, is the only option available for a patient faced with a serious or life-threatening medical condition. The authorization to proceed was granted in the hope of saving the patient’s life.
Organs from genetically modified pigs have been a focal point of much of the research in xenotransplantation. In fact, a pig’s heart is similar in size, weight, and structure to a human’s heart. We’re now living in an age where whatever the storytellers of the yesteryears dreamed up today’s scientists is turning those dreams into reality. Once imaginable only on the pages of science fiction, xenotransplantation is now a reality and with it comes the possibility of saving countless lives.
Brief timeline of animal-to-human heart transplant
Heart transplant using Chimpanzee Heart (1964)
Result: The patient died within 2 hours.
The first heart transplant in a human ever performed was by Hardy in 1964, using a chimpanzee heart, but the patient died within 2 hours. The chimpanzee heart was not large enough to support the circulation and failed within a couple of hours.
Heart transplant using baboon heart (1983)
Result: The patient died 20 days later.
Perhaps the best known clinical cardiac xenotransplantation since Hardy’s attempt was that by Leonard Bailey who transplanted a baboon heart into an infant girl, known as Baby Fae, in 1983. At that time, it was almost impossible to obtain human organs from infants, particularly those with anencephaly, for transplantation into infants with life-threatening congenital heart disease. The surgical procedure in Baby Fae was technically successful, but the graft underwent acute rejection and the patient died 20 days later.
As the graft was necessarily taken from a baboon that was ABO-incompatible with the recipient—as the O blood type is essentially not found in baboons—this might have added to the severity of rejection. Even though cyclosporine had become available by this time, the immunosuppressive therapy was not sufficient to prevent xenograft rejection. This procedure did little to advance progress in xenotransplantation, but it did draw public and medical attention to the dearth of deceased human organs available for infants in need of a transplant.
Barnard’s attempt with Baboon and Chimpanzee (1977)
In 1977, Christiaan Barnard used this technique in an attempt to support (with xenografts) 2 patients in postcardiotomy shock who could not be weaned from cardiopulmonary bypass after routine cardiac surgical procedures. A baboon heart failed rapidly, but a chimpanzee heart supported the patient for 4 days until it was rejected before the patient’s own heart had recovered. Based on the experimental studies of Demikhov, Brock, and Shumway clinical orthotopic heart allotransplantation was first performed by Christiaan Barnard in 1967 in Cape Town. He later developed a technique of heterotopic heart transplantation, which had some advantages in those early days when graft failure from ischemic injury or from acute rejection was not uncommon
Pig and sheep heart transplants in terminally ill patients (1968)
Result: Rejection occurred within minutes
Donald Ross and Denton Cooley transplanted pig and sheep hearts, respectively, in patients who were about to die. Ross preempted Barnard in performing a heterotopic transplantation in the hope that his patient’s native heart would recover good function, but hyperacute rejection occurred within minutes. In a second patient on the same day, he carried out a test by perfusing a pig heart with blood from the heart-lung machine, with the same result of hyperacute rejection, and so did not carry out the transplantation Cooley’s sheep heart suffered a similar fate. There were 2 further reports of pig hearts being transplanted (1 in Poland and 1 in India) but details of the latter case were scarce and mainly through the lay press.
India’s pig heart transplant by Dr Baruah (1997)
Result: The patient died of multiple infections a week later
Dr Dhani Ram Baruah had transplanted a pig’s heart into a 32-year-old man, Purno Saikia, who had a ventricular septal defect, or hole in the heart. With Baruah was an equally controversial Hong Kong-based cardiac surgeon, Dr Jonathan Ho Kei-Shing. Ho had his own run-in with the Chinese government in 1992, when he fit heart valves made from ox tissue — designed by Baruah — into human patients.
Saikia’s surgery, according to Baruah, lasted 15 hours. He died of multiple infections a week later. The survival period determined by the International Society for Heart and Lung Transplantation for xenotransplantation — the transplantation or infusion of any organ from one species to another — to be considered safe for human trial is 90 days.