A history of transplantation

Modern medicine has made transplant surgery much more successful now than it once was. Cambridge University transplant surgeon, Chris Watson, joins Adam Murphy to discuss the history of transplantation starting in the early 20th century...

Adam -  Let's take you right back to 1902. Hungarian Emerich Ullmann transplants the kidney of a dog into another dog. He later repeats the process and places the kidney of a goat into a dog - the first record of xeno transplantation; cross-species transplantation.

Chris W - They didn't get very good results from this. One of the problems was the technique of joining blood vessels hadn't really been sorted out. Carrel in France pioneered that.

Adam - 31 years later, Yurii Voronoy from Ukraine took what was learned and carried out the first human transplant. However, having used a cadaver that had been deceased for a few days prior to the procedure, the patient soon ran into complications, which we have learned from since then.

Chris W - Nowadays, when we take organs out, we flush them with an ice-cold preservation solution, then we can keep kidneys for 24-36 hours and get good results. We can keep livers for 12 hours. Hearts are even more sensitive - we can keep hearts for probably four hours.

Adam - Back then, it wasn't really clear where a renal transplant should go.

Chris W - When Ullmann did his goat into dog, he put it into the scruff of the neck of a dog, as there is lot of spare flesh there. He could put a kidney in. Voronoy put it into the thigh of a patient.The benefit of the thigh was the blood vessels are very superficial and you can watch how much urine it produces, because you can bring the urine to the tube that drains urine from the kidney out onto the surface of the leg, and you can watch the urine drip down. Of course, that's not a very long-lasting solution because you get infection going back up into the kidney.

Adam - Yurii's patient only survived two days and it wouldn't be until the early 1950s when Rene Kuss, Charles Dubost and Marceau Servelle carried out a series of renal transplants that some components of the procedure we know today would begin to fall into place.

Chris W - At that time, the French were using kidneys from donors that had been guillotined, and these were criminals who had been sentenced to death and then their kidneys were removed. Having got fresh kidneys and implanted them, they still had a problem that the kidneys didn't work. They worked for a few hours and then they failed. What they hadn't appreciated was this process that we call rejection. This is something that had been identified as a possible problem back during the war years by a scientist called Peter Medawar. So rejection was clearly a problem that had to be overcome. But rather overcome it, the next pioneer was a gentleman called Joseph Murray working in Boston in the States and he had some identical twins - one of whom had kidney failure, one of whom was fit and well. Given that they're identical, there was no immunological difference between them, so he was able to take a kidney from one twin and put it into the next twin. That continued until the sixties, where chemical immunosuppression was started to be used, pioneered by a surgeon in my own hospital here, Sir Roy Calne, who's long since retired, but he developed both azathioprine and cyclosporine as immunosuppressants, which is what allowed transplantation to take off and allowed us to do successful livers, hearts, lungs, as well as getting good results from kidneys.

Adam - So success. But then as now, Sir Roy Calne couldn't find enough donors for the number of patients sitting on that waiting list.

Chris W - Currently, we've got around about 6,000 people waiting for an organ of some type in the UK. Four and a half thousand adults are waiting for a kidney. There are 100 children waiting for kidney, 250 waiting for a lung, 300 waiting for a heart, and about 600 waiting for a liver transplant. We do about 4,000 transplants a year. If you're waiting for kidney, then you can wait and be kept reasonably healthy on dialysis. If you are waiting for a liver, or a heart, or a lung, then you don't have long to wait before you become too sick. So there is a significant mortality, a significant rate of dying, in patients while they're waiting. That's about 10% if you're on the liver transplant waiting list, and as high 25% if you're waiting for a lung transplant.

Adam - If you do receive your transplant, your life is still dictated by your new organ.

Chris W - On immunosuppression, you need to take tablets daily for as long as the transplants last or in the case of a heart, lung or liver, for the rest of your life. Those tablets have their own side effects and they also have adverse effects. So being immunosuppressed puts you more at risk of infections and being immunosuppressed also makes you more at risk of certain sorts of cancer, particularly cancers where there may be a viral aetiology.

Adam - As you can imagine for those with vulnerable immune systems, the last two years have caused even more disruption, having to shield consistently from the coronavirus. On top of this, both the number of donors and transplantations carried out have decreased by a third as a result of the pandemic.

Chris W - If you remember, most of the ICU beds were full of patients with COVID. We weren't sure whether COVID would be spread to patients having a transplant - the likelihood is we thought it could be. And therefore, the last thing we want to do is to give a viral infection to someone and then start them on immunosuppression. The other problem was many of these transplants require patients to go into an intensive care unit for a short period afterwards - livers, hearts or lungs do for example - and there were no intensive care unit beds. So of the 23 kidney transplant programs in the UK, 21 closed for a period of time during that first lockdown, when COVID was really severe.

Chris S - Chris Watson and interestingly, before the turn of the century, traffic accidents accounted for the majority of donors. But with improved road safety, these days donors are increasingly middle aged individuals who have died of other common conditions.