In unprecedented procedure, man receives genetically modified pig heart

A 57-year-old man with a life-threatening heart disease received the heart of a genetically modified pig. It was an unprecedented and innovative procedure that brings hope to hundreds of thousands of patients with failing organs.

This is the first successful transplant from a pig heart to a human being. The eight-hour surgery was performed in Baltimore on Friday (7). According to surgeons at the University of Maryland Medical Center, as of Monday, the patient, David Bennett Sr., of Maryland, was doing well.

“[O coração de porco] it’s beating, it’s under pressure, it’s like his heart,” said the surgeon who performed the operation, Dr. Bartley Griffith, director of the medical center’s heart transplant program.

“It’s working and looks normal. We’re excited, but we don’t know what tomorrow will bring. This has never been done before.”

Last year 41,354 Americans received an organ transplant. More than half of them received kidneys, according to the NGO United Network for Organ Sharing, which coordinates efforts to source organs for transplant in the country.

But the availability of organs for transplantation lags far behind the demand, and about 12 people who are on the lists to receive a transplanted organ die every day. Last year, 3,817 Americans received hearts from human donors — more than any year before. But the potential demand is even greater.

Scientists have been working intensively to develop pigs whose organs will not be rejected by the human body. In the last decade, gene editing and cloning technologies have accelerated research. The pig heart transplant came months after surgeons in New York successfully implanted a kidney from a genetically modified pig into a brain-dead person.

Researchers hope that procedures like these will usher in a new era in future medicine where there will be no shortage of organs for transplant for the more than half a million Americans who are waiting for kidneys and other organs.

“What we had was a watershed moment,” said Dr. David Klassen, medical director of the United Network for Organ Sharing and a transplant surgeon. “Doors are starting to open that I believe will lead to big changes in the way we treat organ failure.”

But he highlighted that there are still many hurdles to overcome before this procedure can be applied on a large scale, noting that organ rejection occurs even in transplants of a kidney from a compatible human donor.

Family members and doctors of the patient, David Bennett, said he decided to bet on the experimental treatment because he would have died without a new heart, had already exhausted other forms of treatment and was too sick to be considered eligible for a human donor heart.

Its prognosis is uncertain. Bennett is still connected to a bypass cardipulmonar, which was keeping him alive before the surgery. But experts say this is not uncommon in patients who have recently received a transplanted heart.

The new heart is working and is already doing most of the work, and doctors say Bennett can be unplugged from the device as early as Tuesday. He is under careful observation for any signs that his body is rejecting the new organ, but the first 48 hours, which are critical, passed without incident.

Bennett is also being monitored for possible infections, including swine retrovirus, a swine virus that can be transmitted to humans, although this risk is considered small.

“Either I have this transplant or I die,” the patient said before the surgery, according to officials at the University of Maryland Medical Center. “I want to live. I know it’s a long shot, but it’s my last option.”

Griffith said he first brought up the experimental treatment in mid-December in a “memorable and rather awkward” conversation with the patient.

“I said, ‘We can’t give you a human heart—you don’t qualify. But maybe we can use the heart of an animal, a pig. It’s never been done before.”

“I wasn’t sure he understood me,” the doctor continued. “But then he said, ‘So, am I going to start grunting?'”

Xenotransplantation — the process of grafting or transplanting organs or tissues from animals to humans — has a long history. Efforts to use animal blood and skin began hundreds of years ago.

In the 1960s, chimpanzee kidneys were transplanted into some human patients, but the longest a recipient survived was nine months. In 1983, a baby known as Baby Fae was given a baboon heart, but died 20 days later.

Pigs have an advantage over primates when it comes to providing organs for transplants, as they are easier to raise and reach adult human size in six months. Porcine heart valves are routinely transplanted into human patients, and some diabetics have already received porcine pancreatic cells. Pig skin has also been used as a temporary graft in burn patients.

Two more recent technologies — gene editing and cloning — have produced organs from pigs genetically modified to be less likely to be rejected by humans. Pig hearts have already been successfully transplanted into baboons by Dr. Muhammad Mohiuddin, a professor of surgery at the University of Maryland School of Medicine who created the heart xenotransplantation program with Griffith and is its scientific director. But until recently, safety concerns and fears of provoking a dangerous immune response that could put a patient’s life at risk have precluded the use of these organs.

Jay Fishman, deputy director of the transplant center at Massachusetts General Hospital, said the use of pig organs makes possible genetic manipulations, the time needed for better screening to exclude infectious diseases, and the possibility of a new organ at the time the patient needs it.

“There are challenges, no doubt, but also opportunities,” he said.

The heart Bennett received came from a genetically modified pig supplied by Revivicor, a regenerative medicine company based in Blacksburg, Virginia.

The pig received ten genetic modifications. Four genes were deleted or inactivated, including one that encodes a molecule that causes an aggressive human rejection reaction.

A growth gene was also turned off, to stop the pig heart from continuing to grow after it was implanted, said Dr. Mohiuddin, who, with Griffith, did most of the research leading up to the transplant.

Six human genes were inserted into the donor pig’s genome—modifications to make the pig’s organs more tolerable by the human immune system.

The team used a new experimental drug developed in part by Mohiuddin and produced by Kiniksa Pharmaceuticals to suppress the immune system and prevent rejection. She used a new perfusion device to preserve the pig’s heart until surgery.

A FDA (Food and Drug Administration) worked intensively towards the end of the year and on New Year’s Eve finally gave the surgeons an emergency authorization to perform the procedure.

Surgeons were met with several surprises.

“The anatomic aspect was a little tricky. There were some unforeseen moments and we had to do some smart plastic surgery to make it all fit,” said Griffith. When surgeons removed the clamp that restricted blood flow to the organ, “the animal heart immediately began beating and contracting.”

Translation by Clara Allain.