First patient to receive genetically-altered PIG heart transplant dies

BREAKING NEWS: Ex-convict who became the first ever patient to receive a genetically-altered PIG heart transplant has died two months later

  • A Maryland man that received a heart transplant from a pig earlier this year has died
  • The cause of death was not revealed but doctors told reporters his condition had deteriorated over the past several days 
  • Bennet received a groundbreaking transplant where the pig’s heart was genetically modified in a way that would prevent a human body from rejecting it
  • The man was already in desperate condition but did not meet criteria to receive a normal, human transplant

The first person to receive a heart transplant from a pig has died, two months after the groundbreaking experiment, the Maryland hospital that performed the surgery announced Wednesday.

David Bennett, 57, of Hagerstown Maryland, died Tuesday at the University of Maryland Medical Center. Doctors didn´t give an exact cause of death, saying only that his condition had begun deteriorating several days earlier.

Bennett’s son praised the hospital for offering the last-ditch experiment, saying the family hoped it would help further efforts to end the organ shortage.

‘We are grateful for every innovative moment, every crazy dream, every sleepless night that went into this historic effort,’ David Bennett Jr. said in a statement released by the school. 

‘We hope this story can be the beginning of hope and not the end.’

David Bennett (left), died on Wednesday, the University of Maryland Medical Center announced. He received a first of its kind pig heart transplant in January. Doctors did not reveal how he died, but did say his condition deteriorated over the course of several days

A pig heart was gathered for a terminal heart disease patient who was ineligible for a human heart transplant. Scientists inserted six human genes into the genome of the donor pig — modifications designed to make the organ more tolerable to the human immune system. They inactivated four genes, including sugar in its cells that is responsible for that hyper-fast organ rejection and a growth gene to prevent the pig’s heart, which weighs around 267g compared to the average human heart which weighs 303g, from continuing to expand. Surgeons at the University of Maryland Medical Center performed a nine-hour surgery to remove the patient’s heart and insert the altered pig heart

How was the surgery possible? 

David Bennett, a 57-year-old handyman from Baltimore, Maryland, was the first person in the world to receive a pig heart transplant.

The operation was performed as Bennett did not meet the criteria for a human heart transplant and faced dying from heart disease if he did not undergo the operation.

‘It was either die or do this transplant,’ he said. 

He died on March 9, though no cause of death was revealed by doctors 

Have animal organs been transplanted to humans before?

Scientists have been toying with animal-to-human organ donation, known as xenotransplantation, for decades.  

Skin grafts were carried out in the 1800s from a variety of animals to treat wounds, with frogs being the most popular. 

In the 1960s, 13 patients were given chimpanzee kidneys, one of whom returned to work for almost 9 months before suddenly dying. The rest passed away within weeks.

At that time human organ transplants were not available and chronic dialysis was not yet in use. 

In 1983, doctors at Loma Linda University Medical Center in California transplanted a baboon heart into a premature baby born with a fatal heart defect.

Baby Fae lived for just 21 days. The case was controversial months later when it emerged the surgeons did not try to acquire a human heart.

More recently, waiting lists for transplants from dead, or allogenic, donors is growing as life expectancy rises around the world and demand increases. 

In October 2021, surgeons at NYU Langone Health in New York successfully transplanted a pig kidney into a human for the first time.

It started working as it was supposed to, filtering waste and producing urine without triggering a rejection by the recipient’s immune system. 

The recipient was a brain-dead patient in New York with signs of kidney dysfunction whose family agreed to the experiment before she was taken off life support. 

Why would his body not reject the animal organ?

Earlier attempts to insert animal organs into human hearts have largely failed because patients’ bodies rapidly rejected them.

Rejection is caused by the immune system identifying the transplant as a foreign object, triggering a response that will ultimately destroy the transplanted organ or tissue.

Roughly 50 percent of all transplanted human organs are rejected within 10 to 12 years, for comparison.

To give the experimental operation the best chance of success, scientists genetically modified the pig heart to make it more compatible with the human body.

This involved removing a certain sugar in the cells that is known to cause rapid rejection.

A pig heart was used over other animals because pigs are easier to raise and achieve adult human size in six months. Several biotech companies are developing pig organs for human transplant.

After a nine-hour procedure, Mr Bennett is said to be recovering and doing well.

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.

But they warned Mr Bennett’s prognosis is ‘unknown at this point’ and he may only live for days with the pig heart.

What did they do to make sure the pig heart could be used?

Revivicor, a subsidiary of US biotech company United Therapeutics, genetically modified the pig heart that was implanted in Mr Bennett.

Scientists inactivated four genes, including sugar in its cells that is responsible for that hyper-fast organ rejection.

A growth gene was also inactivated to prevent the pig’s heart from continuing to grow after it was implanted.

In addition, six human genes were inserted into the genome of the donor pig — modifications designed to make the organ more tolerable to the human immune system. 

Doctors for decades have sought to one day use animal organs for life-saving transplants. 

Bennett was a candidate for this newest attempt only because he otherwise faced certain death – ineligible for a human heart transplant, bedridden and on life support, and out of other options.

After the January 7 operation, Bennett’s son told The Associated Press his father knew there was no guarantee it would work.

Prior attempts at such transplants — or xenotransplantation — have failed largely because patients´ bodies rapidly rejected the animal organ. 

This time, the Maryland surgeons used a heart from a gene-edited pig: Scientists had modified the animal to remove pig genes that trigger the hyper-fast rejection and add human genes to help the body accept the organ.

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.

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.

Doctors didn’t reveal the exact cause of Bennett’s death. Rejection, infection and other complications are risks for transplant recipients.

But 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 whether scientists have learned enough from Bennett’s experience and some other recent experiments with gene-edited pig organs to 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, surgeons at New York University 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. 

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.

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.

Bennet served a prison sentence 34 years ago for stabbing Edward Shumaker, a Fredrick, Maryland, resident, seven times.

Shumaker’s older sister told the Washington Post that her brother spent the next 19 years wheelchair bound because of the attack.

He died in 2007 as a result of a stroke he suffered in 2005 at the age of 40.

Bennet’s questionable past has opened questions on whether he is deserving of a ‘second chance’ at life. 

There were also concerns raised by some experts at the time that the operation was unethical and was akin to performing a human experiment.

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