TOM LEONARD: A pig’s heart and a human life saved…is this the op that’ll change transplants for ever?
Stricken by terminal heart disease, David Bennett had only one chance left. He had been bedridden in hospital for months with an irregular heartbeat and was connected to a heart-lung machine keeping him alive.
He was deemed too ill for a human transplant — but there was another option, and the 57-year-old grabbed it.
‘I know it’s a shot in the dark but it’s my last choice,’ he said after making the decision.
Dr. Bartley Griffith takes a selfie photo with patient David Bennett in Baltimore in January 2022. Mr Bennett has had a genetically modified pig’s heart transplanted into his body as he was deemed as too ill to have a human organ
Last Friday, the handyman from Baltimore, Maryland, made history as the first person to successfully receive a genetically modified pig’s heart. Delighted doctors say the patient is doing well
The genetically modified pig was specifically bred so it could be used as an organ donor
Last Friday, the handyman from Baltimore, Maryland, made history as the first person to successfully receive a genetically modified pig’s heart. Delighted doctors say the patient is doing well.
They and other medical experts have hailed this groundbreaking procedure as the dawn of an astonishing new era of transplantation. It will give hope to thousands of people with failing organs who have been frustrated by the chronic shortage of human ones.
Researchers have also been studying how to transplant pigs’ lungs, livers and kidneys into humans. All these could now be possible thanks to the most recent procedure.
More than 100,000 people are waiting for organ transplants in the U.S., of whom 1,700 need a heart. In the UK, about 7,000 people are on the transplant waiting list (at least 300 of whom need a heart).
Last year, in Britain, more than 470 people died while waiting for an organ transplant.
However, many will be deeply alarmed, fearing science is once more trampling over basic notions of ethical behaviour towards animals and, indeed, may now be poised to disturb the ‘natural order’ by merging man and other animals.
The potential perils of doing this were most famously — and terrifyingly — explored by H.G. Wells in his novel The Island Of Doctor Moreau.
Researchers have also been studying how to transplant pigs’ lungs, livers and kidneys into humans. All these could now be possible thanks to the most recent procedure
Mr Bennett’s operation was foreshadowed in the novel Pig Heart Boy, by British author Malorie Blackman, in which the transplant proves so divisive that the teenage recipient has a bucket of pig blood poured over him by an outraged animal rights protester.
The animal used in the six-hour operation at the University of Maryland Medical Centre was no ordinary pig. It had been genetically modified, essentially ‘created’ in the laboratory to overcome the problem that has long bedevilled so-called ‘xenotransplants’ — in which the cells, tissues or organs of other species are transplanted into humans — namely the rejection of the foreign body by the human recipient.
In the most famous example of a xenotransplant, dying American infant Stephanie Fae Beauclair — known as Baby Fae — was given a baboon heart in 1984 but lived only 21 days before it was rejected.
In the case of Mr Bennett’s new heart, it was removed from the pig on the morning of surgery and stored in a special preservation chamber. This XVIVO Heart Box, the size of a microwave oven, preserves the heart at 8c (46f) while supplying it with a nutrient-rich oxygenated solution. It was wheeled on a trolley into the operating room where Mr Bennett’s body was waiting to receive it.
The surgery was fairly straightforward compared with the science that had gone into preparing the pig.
Pigs have a gene that produces a molecule, not found in humans, that triggers an immediate and aggressive immune response in humans, called hyperacute rejection. Within minutes, the body attacks the foreign organ.
With Mr Bennett’s porcine heart donor, three of the genes that would have caused the organ to be rejected had been deactivated using a pioneering DNA-editing technique known as CRISPR.
With Mr Bennett’s porcine heart donor, three of the genes that would have caused the organ to be rejected had been deactivated using a pioneering DNA-editing technique known as CRISPR
Another gene, which would have caused the pig heart to grow drastically, was also ‘knocked out’. In addition, six human genes that would dramatically increase the chances of the heart being accepted were inserted into the pig.
Mr Bennett also received an experimental anti-rejection drug. To go ahead with the pig-heart transplant in Maryland, the university had obtained an emergency authorisation from the U.S. Food and Drug Administration on New Year’s Eve through its ‘compassionate use’ programme, which allows risky experimental procedures on people who have no other treatment options.
Pigs have long been an attractive source of potential transplants because their organs are so similar to those of humans and — unlike primates such as chimpanzees and baboons — can be bred in large numbers. A pig heart at the time of slaughter is about the size of an adult human one.
Pig heart valves have been used successfully for decades in humans. Indeed, Mr Bennett himself received one about ten years ago.
Dr Bartley Griffith, the director of the university’s cardiac transplant programme, who performed the operation on Mr Bennett, had transplanted pig hearts into 50 baboons over five years before offering the option to his newest patient.
He said of the transplanted organ: ‘It creates the pulse, it creates the pressure, it is his heart. It’s working and it looks normal. We are thrilled, but we don’t know what tomorrow will bring us. This has never been done before.’
On Monday, the patient was reported to be breathing on his own while still hooked up to a heart-lung machine to help his new organ.
He said he was ‘looking forward to getting out of bed’, although his son acknowledged the family were ‘in the unknown at this point’.
Medical experts hailed the operation as a watershed but, given animal-human transplant history, some were cautious in their response.
On Monday, the patient was reported to be breathing on his own while still hooked up to a heart-lung machine to help his new organ
Sir Terence English, who carried out the UK’s first successful heart transplant in 1979, said: ‘This is a marvellous advance which has enormous potential for the future.
‘With pigs’ hearts, we would no longer have patients on the waiting list, dying, because surgeons cannot get a heart of the right size with the right blood type for them. There would be an off-the-shelf heart available whenever one was needed.’
The ‘major sticking point’, he said, had been eradicating those genes in pigs which are responsible for their organs being rejected in humans. He added: ‘Having mainly achieved this, and with pig organs lasting several months in primates, now was the time to start trying in humans.’
A spokesman for NHS Blood and Transplant said: ‘We have been watching this particular field of research for many years — the possibility of transplant between animals and humans.
‘However, there is still some way to go before transplants of this kind become an everyday reality.’
Francis Wells, consultant cardiac surgeon at the Royal Papworth Hospital near Cambridge, suggested it was too early to declare the operation a success.
‘Although the early function of the heart is vital, it is the mid- and long-term that matters the most,’ he said.
‘As yet, there is no data on this and we wait with interest to learn how this courageous patient progresses.’
The hurdles ahead aren’t only scientific, of course. Animal rights group Peta (People for the Ethical Treatment of Animals) immediately condemned the transplant. ‘Animal-to-human transplants are unethical, dangerous, and a tremendous waste of resources that could be used to fund research that might actually help humans,’ it said in a statement.
‘Animals aren’t toolsheds to be raided but complex, intelligent beings. It would be better for them and healthier for humans to leave them alone and seek cures using modern science.’
Yet xenotransplantation from animals to humans has a surprisingly long history. Throughout the 19th century, doctors treated wounds with skin grafts from various animals, often frogs.
In the 1920s, French surgeon Serge Voronoff developed a procedure for transplanting slices of chimpanzee testicles into older men whose ‘zest for life’ was deteriorating.
He claimed that the hormones produced by the testes would rejuvenate his patients, enhancing not only libido but eyesight and memory. His transplant became enormously popular among millionaires, prompting Voronoff to set up a monkey farm to keep up with demand and develop a monkey ovary transplant after women requested their own version of the treatment.
In the 1960s, scientists transplanted chimpanzee kidneys into 13 patients, one of whom returned to work for almost nine months before suddenly dying from what was believed to be an ‘electrolyte disturbance’.
In 1964, the first heart transplant in a human was performed using a chimpanzee heart, but the patient died within two hours. In October 2021, surgeons notched up a ‘first’ when they attached a kidney grown in a genetically modified pig to a brain-dead human patient. The kidney functioned properly for a 54-hour observation period.
Countries such as the UK and U.S. tightly regulate xenotransplants but other countries do not, a fact that has already prompted researchers to conduct trials in places such as Mexico.
The World Health Organisation has expressed fears of so-called ‘xenotourism’, in which desperate transplant patients resort to going to countries that impose no limits on operations.
A new era may have dawned but, as with other scientific breakthroughs, the future may not be entirely rosy.