How pigs became the ‘beacon of hope’ to solve human organ donation shortages
When surgeons in the United States transplanted a kidney from a genetically modified pig into a living human in March, it was seen as a major milestone in the quest to solve organ shortages across the world.
The lead surgeon was optimistic, saying he believed the kidney could survive for two years.
But nearly two months after he underwent the procedure, 62-year-old Richard “Rick” Slayman has died.
The Massachusetts General Hospital surgical team released a statement this week saying there was “no indication that it was the result of his recent transplant”.
And leaders in xenotransplantation — the transplant of animal organs into humans — remain hopeful that pigs, in particular, are the answer.
So how did pigs become the focus of future organ donation?
Desperate need for non-human alternatives
As of May 1, about 1,400 Australians were waiting for a kidney transplant, the most in-demand organ in the country.
In the US, there are more than 96,500 patients on waitlists.
People are given transplants when their kidney is no longer working and they have been living on dialysis.
Studies show that people with kidney transplants live longer than those who stay on dialysis, according to the National Kidney Foundation.
Wayne Hawthorne, professor of transplantation, and immediate past president of the International Xenotransplantation Association, said it’s not possible for donation rates to meet demands.
At the Westmead National Pancreas and Islet Transplant unit, they have 10 times more patients on the waitlist than they can ever offer a transplant, he said.
“We have been trying for decades to develop, and improve on organ donation from human to human,” Professor Hawthorne told the ABC.
But even with changes to hospital systems and improvements to organ donor rates, organs such as kidneys and hearts remain in short supply as they need to come from “brain-dead donors”.
And these aren’t easy to come across.
“Once your heart stops, you stop breathing and your circulation stops, and your organs are no good,” Professor Hawthorne said.
“That’s the problem, you have to have this circulation.
“So it means we have very, very few organ donors … we’re talking only a few 100 donors per year in Australia, compared to many thousands of patients.”
Why pigs?
For decades, researchers have been exploring the use of transplanted animal organs and tissues in humans.
In 1984, “Baby Fae” became the first infant to undergo a xenotransplant procedure, receiving the heart of a baboon.
The 14-day-old baby from California survived for 21 days.
But although non-human primate organs would be the best match, Professor Hawthorne says there are issues around ethics and supply.
“People don’t like these sorts of animals being used in research, let alone as donors to humans,” he said.
“The other big problem is trying to breed them … like humans, they take a very long time to generate and have single offspring, usually.
“So they’re very, very difficult to generate as organ donors.”
Pig parts are already widely used in human medicine, for things like diabetes insulin and tissue for heart valves.
And, given they have similar organ sizes, it makes pigs the next ideal option.
Gene editing a ‘beacon of hope’
Entire organ transplants have failed over the decades due to people’s immune systems attacking the foreign tissue.
But researchers are now utilising advancements in gene editing to better match animal organs to human bodies.
Mr Slayman became the first living person to receive a modified pig kidney after his human transplant in 2018 failed.
Kidneys from similarly edited pigs had successfully been transplanted into monkeys that were kept alive for an average of 176 days, and in one case for more than two years, researchers reported in October in the journal Nature.
Tatsuo Kawai, who helped lead the transplant team for the procedure, described the pig organ as “truly the most beautiful kidney I have ever seen”.
“The success of this transplant is the culmination of efforts by thousands of scientists and physicians over several decades,” Dr Kawai said in March.
“Our hope is that this transplant approach will offer a lifeline to millions of patients worldwide who are suffering from kidney failure.”
The surgical team is not yet linking Mr Slayman’s death to the transplant and still sees the procedure as “a beacon of hope”.
And Mr Slayman’s family said they are grateful he was given the opportunity for a second chance.
“We felt – and still feel – comforted by the optimism he provided patients desperately waiting for a transplant,” the family said in a statement.
When he was discharged from hospital in early April, Mr Slayman said he was “leaving the hospital today with one of the cleanest bills of health I’ve had in a long time … one I wished would come for many years”.
Toby Coates, the director of transplantation at the Royal Adelaide Hospital, said Mr Slayman’s death is a tragedy, but by no means a setback for xenotransplantation.
“It’s an absolute tragedy, but this has moved the field forward,” he told the ABC.
“It’s quite extraordinary, really, that there’s now been three of these done and this will be the the beginning of a whole lot more.”
Lessons from pig heart transplants
Two men from the US have received genetically-edited pig heart transplants since early 2022.
Fifty-seven-year-old David Bennett was the first person in the world to undergo the procedure. He survived for two months.
While 58-year-old Lawrence Faucette died nearly six weeks after his transplant.
Both men had underlying health issues, but Mr Bennett was found to have a pig-derived infection, which may have contributed to transplant complications.
“Transplant recipients regularly die after a transplant, they’re just so unwell,” Professor Hawthorne said.
“These people were not suitable for human transplants, which means they were even sicker than people that get human transplants.”
Professor Coates said his “gut feeling” is that the poor health of patients before the xenotransplant procedures was a main factor in their deaths.
He added that the use of medications, which lower the body’s ability to reject transplants, can also weaken immune systems.
In all cases, the men were able to live longer than they would have otherwise.
And Professor Hawthorne expects the outcomes to significantly improve over time.
“We didn’t just magically have people surviving with human kidneys for years … The first human kidneys only survived weeks,” he said.
“We’ve been building on the science and the medicine for a long time to get it right, and are very, very slowly, systematically and safely implementing it into patients.”
Where is Australia at?
Australia is leading the world in islet cell transplantation and has been working in parallel with researchers in the US and Europe to enhance xenotransplantation.
But Australia faces restrictions getting the pigs needed for trials into the country, because “we didn’t just start with this magic pig,” Professor Hawthorne said.
And developing local porcine colonies for xenotransplantation would require large financial backing.
“We have spent decades developing our own transgenic pigs for clinical transplants here in Australia and require more support to take these to the clinic,” Professor Hawthorne said.
They have also been working closely with the World Health Organization to ensure strict guidance and ethics.
“The reason we haven’t done these transplants earlier is not just because we didn’t have the transgenic pig,” he said.
“We didn’t want to make any mistakes … we wanted to get the ethics and all of our background research right to the point where we can provide safe and efficacious xenotransplants.”
SOURCE: ABCNEWS