Saturday, January 22

Why Pig-to-Human Heart Transplantation Is Only The Last Resort For Now | Medical Investigation

The world’s first transplant of a genetically altered pig heart into a diseased human is a milestone for medical science, but the operation, and the overall approach, raises substantial safety and ethical concerns.

Surgeons at the University of Maryland Medical Center spent eight hours Friday night transplanting a heart from the pig to David Bennett, 57, who had been in the hospital for more than a month with end-stage heart failure.

It was an exceptional procedure. Doctors deemed Bennett facing near certain death and deemed him too ill to qualify for a routine human heart transplant. As a last resort, the medical team sought emergency clearance from the Food and Drug Administration (FDA) to transplant a heart from a genetically altered pig.

The heart came from a pig created by Revivicor, a spin-out of PPL Therapeutics, the UK company that created Dolly the Sheep in 1996. Now under US ownership, Revivicor pigs are designed to prevent immune rejection. Among the genetic alterations made are adjustments that eliminate a sugar molecule from the tissues that causes the rejection of the organ. The FDA approved the operation, along with the team’s proposal to use an experimental drug to prevent Bennett’s body from rejecting the organ.

Dr. Bartley Griffith takes a selfie photo with David Bennett in Baltimore in January 2022.
Dr. Bartley Griffith with David Bennett, the world’s first human to receive a pig heart. Photograph: Bartley Griffith / AP

On Monday, doctors at the hospital said Bennett was awake and breathing alone, but that it was too early to say the operation had been a success. Doctors are waiting to see how Bennett does in the days, weeks, and hopefully months to come.

The prospect of removing organs from animals to save human lives has a long and checkered history. Advocates see the approach as a way to reduce waiting lists for desperately ill patients, while animal rights activists see it as dangerous and ethically abhorrent. In the 1960s, American doctors transplanted chimpanzee kidneys in more than a dozen patients, all but one of whom died within weeks. In the 1980s, a premature baby in California received a baboon heart but died three weeks later.

The main risk is immune rejection: even with human donor organs, recipients need constant immunosuppression to prevent their bodies from attacking transplants. While Revivicor’s pig heart is designed to be less prone to immune rejection than standard animal organs, it is unclear how well it will be tolerated by the body. Because the organ comes from another species, Bennett will need stronger immunosuppression than usual, which carries its own medical risks.

Recent work on such donor animals has focused on pigs because, although they have different immune systems than humans, the animals’ organs are very similar. While much of the effort has gone into making pig organs invisible to the human immune system, it is far from the only challenge. In the 1990s, scientists practically abandoned their work with donor pigs when they realized that the retroviruses lurking in the DNA of animals could potentially infect human cells. That raised the worrying prospect that transplanted organs will spread infections to vulnerable patients who received them.

Research has been done to overcome the problem, taking genome editing to another level. After modifying pig DNA to remove molecules that trigger immune rejection, scientists have made precision alterations that remove dozens of retroviruses from pig tissues in the hope that organs will be safer when they are finally transplanted. .

How well animal organs function will be up to clinical trials, rather than one-time operations. Many biotech companies are moving cautiously, setting up trials to see if organs are safe and effective, first in other animals and then in humans. For those with defective organs, hope for now remains in the generosity of human donors.

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