Vain, some might even say reckless, surgeon Christiaan Barnard took a buccaneering approach to organ transplantation. In 1960, he added a second head to a dog. But just seven years later, he achieved global celebrity by performing the world’s first successful human heart transplant.
Now, 20 years after Barnard’s death, another medical milestone has been crossed, with the first successful transplantation of a pig’s heart into a human – David Bennett, 57, a man so sick that regulators granted exceptional approval to doctors attempting to save his life with the procedure.
The news came as no surprise to Prof Bruno Reichart, who, in 1984, succeeded Barnard as professor of surgery at Groote Schuur Hospital in Cape Town. Four decades ago, Prof Reichart, now 78, performed Germany’s first heart transplant. In recent years, however, he has become a staunch advocate of “xenotransplantation” – the use of animal organs in people. It is, he argues, the only way to cut transplant waiting lists, estimated to stand at more than 7,000 in the UK, with almost 500 dying each year while they wait. At Reichart’s 75th birthday party in 2018, he predicted it would be three years until the first pig-human transplant. He was right.
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“It’s great news,” he says of Bennett’s operation, performed by a team at the University of Maryland in America. News that might, according to Prof Gabriel Oniscu, director of the Edinburgh Transplant Centre, enable xenotransplants to happen on the NHS in “about five to 10 years”.
David Bennett, 57, was the successful recipient of a pig's heart Credit: University of Maryland School of Medicine (UMSOM)/Handout via REUTERS
For those who feel squeamish at the idea of implanting animal organs in humans, Reichart offers reassurance: “There’s no stigma. There should be no ethical concerns.” And in any case, he adds, the heart in question is not really just a pig’s heart, which would be recognised and rejected “within an hour”. “You need to humanise a porcine heart,” he says, talking with the enthusiasm and energy of a man still fascinated and invigorated by his field of expertise. “Which means it’s a half-pig, half-human heart.”
That process of humanisation involved 10 genetic modifications of the pig heart, nine of which tweaked it to make it more acceptable to the human body. The last kept the heart small – just the right size for a person. “You don’t want a 1kg heart in your chest – you’d die,” says Reichart. “You need to mitigate growth, my team found that out. So you need small pigs” – ones that weigh between 70 and 90kg, not the huge 300kg porkers bred for bacon.
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The company breeding that special pig has a connection even closer to home. Revivicor, which provided the genetically modified pig to the Maryland team, is a spin-off from PPL Therapeutics, the British company which, in 1996, bred the world’s first cloned animal – Dolly the Sheep.
And Revivicor’s parent company, United Therapeutics, doesn’t just have pigs’ hearts on its human transplant menu. Genetically tweaked pig kidneys are also in the works, for patients with late-stage renal disease. Indeed, a pig kidney was first attached (and I do mean attached, being strapped on outside the body) to a 66-year-old brain-dead woman in a two-hour operation last October.
It doesn’t stop there. Researchers are working on pig skin for human burn victims. At the University of Alabama in Birmginhman’s xenotransplantation centre, experts suggest genetically modified pigs could even produce blood suitable for human transfusion, or dopamine for Parkinson’s sufferers. The first pigs bred to produce islet cells, which fail in diabetes patients, were born in 2013 and transplanted pig corneas were last year shown to offer significant improvement in patients with keratoconus, which can cause severe loss of vision.
Pigs have become the donor animal of choice, and the subject of decades of research, which only entrenches their use in future xenotransplantation study Credit: dusanpetkovic
The latter was a throwback to the very dawn of the xenotransplant era itself – 1838, when Dr Richard Kissam, an ophthalmologist in New York, cut out the opaque cornea from a sensationally brave Irishman and replaced it with one from a six-month- old pig, attached with two stitches. Immediate results were encouraging. Within two weeks, though, the new cornea clouded over.
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That was 67 years before the first human cornea transplant, performed by Dr Eduard Zirm on a labourer blinded in an accident. This time, as if by magic, the patient fully regained – and kept – his sight. But xenotransplant fans had not given up. In the same year, 1905, slices of rabbit kidney were implanted into a severely ill patient. Remarkably, the patient survived for 16 days.
It wasn’t until 1954 that the first major human organ transplant – of the kidneys – took place. But animal transplants had still not disappeared. In 1963, a patient survived for nine months after receiving chimpanzee kidneys. And in 1964, as Barnard closed in on his world first, Dr James Hardy performed the first chimpanzee-human heart transplant. (His patient lasted just two hours.)
Indeed, the apes which most resemble us remain the most suitable animal organ donors. “Non-human primates are the best,” says Reichart, “but, of course, there is a major ethical constraint. Some are endangered, and even if you discount that, they have long pregnancies, and have only one or two offspring.” Pigs, by contrast, have shorter pregnancies and produce around a dozen piglets.
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And, of course, we already eat them: “I’m not saying there are no ethical barriers, but it’s easier.” Hence pigs have become the donor animal of choice, and the subject of decades of research, which only entrenches their use in future xenotransplantation study. Ultimately, however, animals may no longer be required, as technology matures that allows scientists to grow organs (or, indeed, meat) in the lab. At the Crick Institute in London, Dr Paola Bonfanti leads a team building a thymus, a mini-organ which is vital for the development of T-lymphocytes, which fight infections and cancerous cells. There are, she says, “intrinsic biological complexities” in building organs. Scaffolds are required on which to mount the vast numbers of cells required, and then there is the challenge of plugging them into the circulatory system to keep them alive.
“It’s hard for small organs,” she says. For larger organs – the heart, the lungs – it will be much harder still. The first step, she says, will be to build something big enough to replace at least part of the function of the failing organ.
Then there is the law. Bonfanti hopes to have her thymus ready in the lab in five years and is already designing a clinical trial. But it may take much longer to win regulatory approval. And that is where the Maryland breakthrough has given xenotransplantation a big advantage in what can sometimes feel like a race between lab-grown and animal transplants. “I’m curious to see how this is going to work,” she says of the pig transplant. “If the pig organ is fully invisible [to the immune response], it may be an alternative. But we do not yet know the long-term immunological complications. We need to wait.”
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Back in Germany, Reichart dismisses such uncertainty. He talks wistfully, perhaps even with a touch of the envy that drives many vastly ambitious researchers, about the Maryland operation. In the distant past, he acknowledges, corners were cut in the desperate quest to forge ahead. “Barnard,” he concedes, “needed to ask more questions.”
But when it comes to pig transplants, he thinks, a frontier has now irrevocably been crossed. There’s no going back. “It’s done. I think we can all now proceed,” he says. “People should be excited.”
