50 years of heart transplant
3 December 2017 marked 50 years since the first heart transplant. Thousands of patients have since been saved, but there are still challenges. Sarah Brealey explains how we’re meeting them.
Christiaan Barnard performs the first human heart transplant at Groote Shuur Hospital, Cape Town.
Fifty years ago, history was made with the first human heart transplant. The patient, Louis Washkansky, 53, was terminally ill with heart failure. His surgeon at Groote Schuur Hospital in Cape Town, South Africa was Christiaan Barnard. The donor, Denise Darvall, was just 25. She suffered a fatal brain injury after a car accident in which her mother also died. Her father, Edward, who knew his daughter loved to help others, took the generous decision to donate her organs (one of Denise’s kidneys also saved the life of a 10-year-old boy).
Louis’s first words after the transplant were: “I’m still alive.” But he died of pneumonia 18 days later.
The kidney was the first organ to be successfully transplanted, in 1954
It was a dramatic development built on previous advances. The kidney was the first organ to be successfully transplanted, in 1954, followed by a simultaneous kidney and pancreas transplant in 1966 and a liver transplant in 1967. Unsuccessful human heart transplants had been tried as early as 1905.
The British Heart Foundation played an important role in the development of heart transplant – even if the first application for funding wasn’t taken entirely seriously. Donald Longmore, who was Consultant Surgeon and Clinical Physiologist at the National Heart Hospital from 1963 to 1980, later said: “We applied for a British Heart Foundation grant, Sir Thomas Sellors and me, in 1963, and we were told that the roars of laughter could be heard two or three blocks away...”
But grant-givers soon started to take it more seriously. “In late 1963, we got a [BHF] grant of £6,000, which in those days was a very large sum of money, and I rented a laboratory in the Royal Veterinary College for six old pence a year, and we set about what we thought was a very scientific approach... doing heart-lung transplants [on animals].”
Louis Washkansky recovers from his heart transplant operation in 1967
Early heart transplant controversy
The early years of transplant were difficult. There were questions of ethics. How could you decide that someone was ‘dead’ when their heart was still beating (which is essential for transplant)? At the time, no definition of ‘brain death’ had been established.
In the UK, this would later be addressed by the Report of the Medical Royal Colleges and their Faculties in 1976 which defined a clinical diagnosis of brainstem death and equated this to death of the patient - a very significant advance for heart transplantation because it enabled donor hearts to be removed in good condition from brainstem dead donors while they were still on a ventilator. Sir Terence English, one of the pioneers of UK heart transplant surgery, says: "This, and our research in 1977/78 on how to store hearts for prolonged periods, meant that we could envisage retrieving donor hearts from all over the UK and parts of Europe."
In the early days, finding donors was difficult. There was criticism from the media and the medical profession. In 1968, The Guardian quoted a consultant cardiologist at the London Hospital describing heart transplantation as “almost amounting to cannibalism”.
David Hamilton, a retired transplant surgeon in Glasgow and a medical historian, says: “Right at the beginning, the opinion was that transplantation was not only impossible but unethical, it was intervening in a way that shouldn’t be done. Now when we see heart transplant almost as a routine operation, the resistance to it at the beginning seems quite incredible.”
Now when we see heart transplant almost as a routine operation, the resistance to it at the beginning seems quite incredible
Retired transplant surgeon and medical historian
The first heart transplant in the UK, on 3 May 1968, was the tenth in the world. It was done at the National Heart Hospital in London. It was performed by Donald Ross (who was funded by the BHF for a further 20 years of surgical advances).
The recipient was Fred West, 45, and the donor was Patrick Ryan, a building worker who had suffered a terrible head injury in a workplace accident, which he could not have survived. Even so, there were wild claims (which doctors proved false at an inquest packed with journalists) that Mr Ryan was murdered for his heart.
There was a media frenzy and transplant surgeons found themselves on the front cover of Private Eye in June 1968. Even some of the doctors involved felt uncomfortable about some aspects. Dr Jane Somerville, who was physician for the first transplant operation, later recalled “the absolute horror of seeing a live patient without a heart in their chest... almost a revulsion.”
Donald Ross later said: “We were excited about sewing in the heart, which is in fact, when you think about it technically, quite a simple plumbing job.”
Sir Keith Ross, another of the surgeons involved in that operation, later recalled: “It was an intensely dramatic moment, I think for everybody there, as it [the heart] went pink and began to beat... One was aware, very much I think, that this was an historic moment and slightly unreal in the relative calm of the operating theatre at the National Heart Hospital.”
Fred West survived for 45 days. After a spate of heart transplants in 1968 and 1969, it became obvious that the survival rates were not getting any better. They were stopped in the UK, and for the most part around the world, until 1979.
Press conference after the first UK heart transplant in 1968
Advances in heart transplantation
It was the discovery of ciclosporin, an immunosuppressant that stopped the body rejecting the heart, that helped make heart transplant successful.
Mr Hamilton says: “Ciclosporin revolutionised transplantation, but it was a difficult drug to use. It wasn’t an overnight revolution. It was toxic to kidneys, so it was a balance between poisoning the kidney and stopping the organ from being rejected.”
Contributing to the advances were BHF-funded surgeons including Magdi Yacoub and Terence English in the late 1970s and 1980s. Sir Terence performed the UK’s first transplant with long-term success on August 18 1979. The patient, Keith Castle, lived for more than five years. The BHF-funded Heart Transplant Research Group was established with Sir Terence as Honorary Director in 1980. All this work contributed to making heart transplant a procedure that would extend the lives of more than half of recipients by 10 years.
Ongoing heart transplant challenges
But 50 years on, there are still challenges. Shortages of donor organs remain a problem, in part because fewer people now die in circumstances that would lead to their organs being suitable for transplant, in particular, traffic accidents. In 2015, surgeon Stephen Large at Papworth Hospital carried out Europe’s first transplant from a non-beating heart donor. This technique was used for the first time in Australia the previous year, and uses a machine to supply the heart with warm, oxygenated blood once it is removed from a donor. This is helping to increase supply of organs, but not enough.
For those who receive a heart, the biggest problem remains rejection, and the BHF is funding several research projects in this area, worth millions of pounds.
Gavin Pettigrew, a transplant surgeon at Addenbrooke’s Hospital, has received BHF funding for his research into chronic rejection in heart transplant. He says this has been the crucial issue since the early days of transplant.
For those who receive a heart, the biggest problem remains rejection
“When organ transplant was first developed, it was felt it would only be a matter of time, and probably just a few years, before we could effectively alter the immune response and get the body to accept the transplant without the need for long-term immune suppression,” he says. “That initial optimism has been tempered by lack of impact – this still remains the holy grail of immune suppression.”
Existing anti-rejection drugs come with a number of problems. “They have to be taken for the rest of your life,” says Mr Pettigrew. “They cause side effects. They carry an increased risk of infection. You also increase the risk of cancer, because a lot of cancers are destroyed in the early stages by the immune system.” Immediate rejection is now relatively rare, but as Mr Pettigrew explains: “The problem is a long-term gradual deterioration of function. Most transplants don’t last beyond about 15 years. For most transplant recipients it means the transplant will not last the rest of their life. We think this is caused by the immune response against the organ, even with anti-rejection drugs. If we could change that, we would give patients a better chance.”
His research is looking at the processes in the immune system that cause rejection, specifically how antibodies that target the transplanted organs develop. “If we can find the key pathways involved in producing antibodies, that would help us develop targeted drugs that would have a specific effect on that pathway, without affecting other parts of the immune system,” he says. “That could really improve patient survival.”
BHF transplant research
We are funding heart transplant research projects around the UK, to reduce the risk of rejection and improve long-term outcomes. One project, at King’s College London, is looking at how to give children who have heart transplants the best chance of survival.
Meanwhile, one of our most senior researchers, Professor Federica Marelli-Berg, BHF Professor of Cardiovascular Immunology at Queen Mary University of London, is trying to ‘hijack’ the immune system to stop it attacking the transplanted heart.