THE SUNDAY TELEGRAPH – 17 September 1995
Behind the hype: monkeys die and the mysteries remain
Transgenic transplants mean grappling with the fundamentals of biology – and success is still a long way off.
MY first kidney transplant operation was on a builder in his early 30s whose kidneys had packed up three years previously, and who had been kept going with dialysis three times a week.
Having removed the now defunct kidneys, the operation then proceeded in two stages. First, the transplant was hitched up to a blood supply, and then the ureter, the thin tube down which the urine travels, was hitched to the bladder.
To our wonder and delight, even before we had got to the second stage. a few precious drops of the golden liquid were already dripping out of the end of the ureter. The patient, when he came round from the anaesthetic, was even more thrilled and in the next few days would inform everyone in earshot of the unbelievable ecstasy at being able to urinate normally again.
Anything that allows as large a number of kidney patients as possible to benefit from this miracle of modern medicine is to be welcomed, and if the transplantable kidneys are to come from pigs, the philosophical problems seem no more profound than whether or not to have bacon for breakfast. Regrettably, despite the promise this week from scientists in Cambridge that the first pig-to-human transplants will start next spring, the full results on which this prediction is based as published in the Lancet on Friday suggests this is a gross example of scientists’ hype. They are appalling.
The experiments involved transplanting the hearts of transgenically altered pigs into the abdomens of 10 monkeys, so though beating as well as the monkeys’ own hearts, they were not actually supporting life.
But despite the fact that these transplanted hearts were not even keeping the monkeys alive, eight had died within two months, leaving just two survivors. These results are actually no better than the first monkey-to-man kidney transplants performed over 30 years ago – long before it was envisaged they might be genetically altered to be more compatible with humans – where one man lived for 63 days and a woman for almost a year.
The dreadful carnage in this series of experiments with an 80 per cent mortality rate at two months compares with the current survival rate of 80 per cent at two years in human-to-human heart transplants, and therein lies a crucial problem. Transgenic pig-to-human transplants must be at least comparably successful to ordinary transplantation if they are to be considered an alternative – and at the moment they are not even past the starting mark. Put another way, no one in his right mind would willingly volunteer for a transgenic transplant on the basis of these results, as long as there remained at least the option of having an ordinary transplant.
The success rate of heart transplants has certainly improved markedly over the past two decades and thus it might be reasonable to infer that the same will be true in the future for transgenic transplants. But this is to underestimate what the scientists are trying to achieve. Heart transplantation is now more successful because, though it seems clever, it is really little more than sophisticated plumbing – taking out a defective heart and plumbing in a new one. And like any technical procedure the more it is done, the easier it becomes.
But trying to create a transgenic pig whose tissues are compatible with humans involves grappling with the fundamental mysteries of biology. The immune system has to be astonishingly complcated just because it needs to differentiate between foreign cells – such as bacteria or transplanted organs – whose purpose it is to destroy and the body’s own cells that it must leave alone.
But despite 40 years of intensive research, the mechanism by which the immune system does discriminate between "self" and "non-self" is still not understood. Perhaps when it is transgenic transplants may be in with a chance, but that prospect is still a long way off.
In the meantime, perhaps we should spare some sympathy for the unfortunate monkeys whose sacrifice at the moment seems so purposeless.
Copyright: Telegraph Group Ltd