An American company that successfully transplanted a pig kidney into a man has revealed an ambitious plan to place pig hearts into the bodies of babies with life-threatening defects from later this year.
In a tour of their plant in Cambridge, Massachusetts, the biotech company eGenesis said it offered hope to millions of people on organ donor lists worldwide.
Mike Curtis, its chief executive and president, believes animal-to-human transplants, known as xenotransplantation, will not only one day eliminate kidney waiting lists but also remove the need for dialysis entirely, while helping thousands of babies who die each year due to critical congenital heart failure.
“It’s a scale which we think is achievable, but it won’t happen overnight,” Curtis said. The company is conducting live trials of genetically modified pig heart and liver transplants with primates.
Last year, paediatric surgeons at the University of Southern California began transplanting pig hearts developed by eGenesis into baby baboons. The goal is to be able to use the organs to replace the hearts of human babies born with serious defects, creating a “bridge” of about 100 days until a human donor becomes available.
At present about half of the 7,200 babies born each year in the US with critical congenital heart disease will die waiting for a transplant.
Curtis said they were seeing promising results, with one baboon surviving 240 days. “So far, it looks really good,” Curtis said.
eGenesis plans to request permission from the US Food and Drug Administration to attempt its first pig-to-human heart transplants later this year.
In the US alone, more than 100,000 people are waiting for a kidney, liver or heart to become available from a human donor. In the UK, 430 people died waiting for such a transplant last year.
Another half a million people in the US receive dialysis, a debilitating treatment that erodes the health of patients who do not yet qualify for a kidney transplant.
With a potentially endless supply of genetically modified pigs, Curtis believes that adverse perceptions about animal organs will soon fade away as more successful transplants are carried out. “People who haven’t faced dialysis or end-stage renal failure don’t really know what they’re talking about,” he said. “When you find yourself in that situation, your willingness to explore options that might have seemed strange before is totally different.”
On March 16 Rick Slayman, a 62-year-old Department of Transportation systems manager from Weymouth, Massachusetts, became the first patient to receive a kidney from a Yucatan miniature pig. The donation from the pig named Patrick came after a human transplant failed in 2018 and Slayman was left with a 1 per cent chance of finding another human match.
So far, Slayman’s new kidney has behaved exactly like a human’s would, regulating his water and mineral balance and excreting waste in the urine. “Everyone was on their A game because there’s so many things that can go wrong,” Curtis said. “Once we said go, it went incredibly smoothly.”
Slayman said he agreed to the transplant not just as a way to help himself, but to provide hope for the “thousands of people who need a transplant to survive”.
However, other pig transplant cases have not been so successful.
In 2022, doctors at the University of Maryland Medical Center (UMMC) performed the first transplant of a genetically altered pig heart into a human. David Bennett Sr, 57, had end-stage heart failure, and did not qualify for a traditional heart transplant. He survived for two months before his new heart gave out.
David Bennett Jr, his son, said his father had an “insatiable will to live” and the family were grateful for “every innovative moment, every crazy dream, every sleepless night that went into this historic effort”.
A study published in The Lancet found that Bennett’s body had not rejected the heart, but that his poor health and severely immuno-compromised condition led to the organ failing.
In September last year, Lawrence Faucette became the second patient to receive a pig’s heart. Faucette, a navy veteran and father of two, initially seemed to be recovering well from the operation at UMMC. About six weeks later, however, his body began showing signs of rejecting the new organ, and he died on October 30.
Bartley P Griffith, a UMMC surgeon who performed both heart transplants, said he was optimistic the knowledge gained from recent surgeries would “up the odds” of survival for the next pig organ recipients. He said Slayman’s recovery was highly encouraging, and that more studies were needed.
“The demand is huge if we can establish effectiveness,” he added. “Even smaller successes drive the imagination, attract research and corporate funding for drugs and engineered pigs, and make the field compelling for our best and brightest physicians and scientists.”
David Klassen, chief medical officer at the non-profit United Network for Organ Sharing, which manages procurement and transplants, said that careful testing under clinical trials was still needed. “Xenotransplantation has the potential to eventually help people in need, but there is much left to learn before xenotransplantation could be offered on a wider scale,” he said.
Wenning Qin, who is in charge of the gene-editing process, took The Times on a tour of the eGenesis facility, explaining how scientists take a piece of skin from the ear of the pig before using enzymes to break the sample down into single cells.
Pigs were chosen over primates for their organ size, large litters and relative ease to breed.
In the case of Rick Slayman, who successfully received a pig kidney in March, Patrick the Yucatan’s cells were edited 69 times over the course of a month, the most carried out on a living animal. This crucial step allows scientists to remove harmful HIV-like pathogens known as porcine endogenous retroviruses, along with the antigens that can trigger rejection by the human immune system.
In 1997, a global moratorium was declared on animal-to-human transplants due to fears that the retroviruses could be transmitted to humans. The global ban was only lifted after the emergence of new technologies — in particular the Crispr gene-editing tool — that allowed scientists to remove the problematic genes.
Porcine genes are knocked out, and replaced with human genes, and the cells are fed nutrients such as protein, sugar and fatty acids, and fused with a donor egg cell. To turn the cells into a living animal, they are cloned using a similar technique to Dolly the sheep.
The resulting embryo is implanted in a sow at eGenesis’s research facility in Wisconsin, and the genetically altered piglets are born by C-section about four months later. The environment is kept as sterile as a hospital operating theatre, to keep the animals free from infection.
And much like the bloodlines of thoroughbred horses, a stable cell line from a pedigree pig can produce thousands of donors.
