Richard was given dialysis to stabilize his condition, and the surgeons performed every test they could think of. They drew samples of blood to check the blood groups matched. They did. They rang up the brothers' family doctor to see if they had shared the same placenta in the womb. They had. The surgeons examined their eyes to see if they were exactly the same colour. They were. Murray even took the brothers down to the local police station to have the detectives check whether their fingerprints were identical.
In all, the surgeons carried out some seventeen tests and the brothers passed every one, but they would have to wait a month for the results of the most crucial test. Murray had transplanted a small piece of skin from Ronald to Richard. If the graft were successful, the surgeons would be in a position to make the final decision as to whether to go ahead with a kidney transplant.
The pressure on the surgeons to operate was building. The press had got wind of the transplant operation. When the brothers had been fingerprinted, crime reporters hanging around the police station had started asking questions. Soon the news was all over the newspapers. But the surgeons could deal with the media; the bigger problem came from Richard himself. After more than a month in hospital his condition was, once again, deteriorating. Despite the dialysis, Richard's heart was starting to fail. His death would be only a matter of time.
Ronald visited him every day at the hospital. The family knew that Richard wasn't going to make it. The surgeons were certain that his death was imminent. If the operation went ahead, there was every chance that Richard could die on the operating table. Even Ronald started to have second thoughts. He was young and healthy – what were his own chances in life if he gave up a kidney? Ronald loved his brother more than anyone else in the world (both their parents were dead), but what if they both died during the operation? Having a kidney removed was in itself a major operation. Would the surgeon who operated on him be competent and experienced? After a lot of soul-searching, Ronald came to the conclusion that he would go ahead and donate his kidney. Then, despite knowing he would definitely die without the operation, Richard tried to persuade his brother to pull out. He even wrote a note telling him to get out of the hospital and go home. But Ronald had made up his mind.
Even the surgeons were beginning to wonder if this was the right thing to do. They had been assured that removing a kidney from a healthy adult had no adverse long-term effect on health or life expectancy. Nevertheless, they consulted psychiatrists, lawyers and even local clergy. Was it morally and ethically right to remove a perfectly healthy kidney from a living donor? Richard was becoming sicker by the day and time was running out. With the skin graft showing no signs of rejection and with Ronald's full consent the surgeons eventually reached a decision.
JOINED AT THE HIP
Peter Bent Brigham Hospital, 23 December 1954
* * *
The two operating theatres are next door to each other. Ronald and Richard Herrick both lie unconscious, shrouded in linen sheets, their bodies illuminated by the bright operating-theatre lights. Each of the twins is surrounded by a team of masked surgeons, nurses and anaesthetists. Every conceivable instrument that might be required is laid out ready. Drips are set up for blood and plasma transfusions; there are swabs, needles, knives and tweezers. The surgeons have practised on cadavers. Joseph Murray has worked through the operation a thousand times in his head. At 8.15 a.m. he is ready to start.
The surgeons removing the kidney from Ronald feel the strain as much as Murray. This is the only compatible kidney on the planet. If they mess it up, Richard will die and they could put Ronald's life at risk. Each team works slowly and carefully, Dr J. Hartwell Harrison on Ronald, Dr Murray on Richard. By 9.50, Harrison has exposed the blood vessels leading to Ronald's kidney. He is ready to sever the blood supply and remove the organ. In the operating theatre next door Murray has prepared the site in Richard's pelvis where the kidney will be reconnected. Everyone pauses. Murray takes a deep breath and gives the instruction to remove Ronald's kidney.
At exactly 9.53 a.m. the surgeons wrap the donated kidney in a cold wet towel and carry it through to Murray's operating theatre. Murray knows he has to reattach the severed kidney as quickly as possible to re-establish the blood supply. The fist-sized organ is sitting in a stainless-steel bowl. Who knows how long it will last?
The clock is running.
Murray has already clamped off the iliac artery in Richard's pelvis at the very top of his right leg. Now he begins to sew. As Carrel had discovered, joining together blood vessels is a slow and precise procedure, but half an hour later the surgeon has successfully connected the artery of Ronald's donor kidney to the artery in Richard's leg.
Murray works methodically and precisely. Everyone is anxious. Is he taking too long? He tries not to look up at the clock. It is 10.40 a.m.
Now he needs to connect the vein from the kidney to the vein in Richard's leg. It is slow work but he can't get distracted by the clock. After thirty-five minutes the veins are joined.
Murray makes a final check to see if everything is OK. Ronald's donated kidney has been out of his body – and without a blood supply – for a total of one hour and twenty-two minutes. Will it still work?
Everyone goes quiet; they can hardly breathe with the tension. The surgeons gently loosen the clamps around the blood vessels. The blood begins to flow. The transplanted kidney becomes engorged. It turns pink, pulsing with blood.
There is a collective sigh of relief; Murray even allows himself a smile. Within minutes, urine starts spurting from a catheter on to the floor. They mop it up and connect the ureter to Richard's bladder. The transplanted kidney is working perfectly.
The next day Richard is feeling better than he has for months. His eyes are bright, he is alert and hungry. Richard and Ronald are discharged from hospital in February. They are both fit and healthy. X-rays confirm that Richard's new kidney is functioning well. As the newspapers put it, this surgery was truly a 'medical miracle'.
Richard went on to marry his nurse and father two children (not identical twins). He lived for another eight years, eventually dying of a recurrence of kidney disease. The surgeons had proved that with identical twins the immune system could be beaten. Over the next few years they tried the procedure on several more sets of twins with equal success.
The surgical techniques developed by the Boston team continue to be used to this day in the tens of thousands of kidney transplant operations that take place every year. But twins represented only a tiny proportion of the people who needed kidney transplants. Understandably, Murray wanted to treat all his patients. He wanted to be able to offer a kidney transplant to anyone in need. The only way to do this was to take on the immune system, and he believed he had just the thing.
THE NUCLEAR OPTION
United States, 1957
* * *
Welcome to the atomic age, where nuclear energy makes everything possible. Why not vacation in Las Vegas – the 'Atomic City' – to see the awesome power of the atom for yourself? While you're there, you could get yourself an atomic hairdo and head off to a 'Dawn Bomb Party' in the desert to witness the latest nuclear test. You could take an atomic box lunch before heading back to the city to sip an atomic cocktail while watching the Miss Atomic Bomb contest. You might even get to see the lucky winner posing in her dazzling white mushroom cloud outfit.
Nuclear tests were the biggest thing that had ever happened to tourism in Nevada, and the crowds flocked from all parts of the USA to see the flash, feel the heat and witness the cloud. But it wasn't just in the desert that the atomic age was capturing the imagination. Right across America there was talk of nuclear-powered rockets and cars. Every home would soon have its own nuclear reactor; housewives would preserve and cook food with the wonders of atomic rays. The US military was spending some $70 million a year on a nuclear-powered aeroplane (although it still had to overcome a few issues with safety). The dream of cheap, clean, nuclear energy was being realized. Nuclear was the f
uture and the future was now!
Medicine was no stranger to the wonders of the atom. X-rays had revolutionized diagnosis and allowed surgeons to see moving images of the inside of the body (see Chapter 2). Radiation was also being used to treat cancer, helping to save many thousands of lives a year. Other doctors were studying the biological effects of radiation – vital to refine treatments, ensure people's safety and, of course, plan for the aftermath of a Third World War.
Ever since the first atomic bombs were dropped on Japan in 1945, scientists had been building up a better understanding of the effects of radiation on the human body. Doctors had been able to examine victims of radiation sickness as their symptoms progressed from vomiting, diarrhoea and fatigue to the full-blown and invariably terminal signs – hair loss, uncontrolled bleeding and heart failure. They found that some parts of the body were affected more than others, and when scientists started to look at individual cells (often during post-mortems) they concluded that some cells were more sensitive to radiation than others. The most vulnerable cells turned out to be those that line the intestine (hence the vomiting and diarrhoea) and also the cells of the immune system – the white blood cells. Enough radiation and the immune system could be completely wiped out. This discovery got the transplant surgeons thinking. Could radiation be used to overcome the body's defences and break down the barrier to successful organ transplants?
A few experiments were tried on animals with varying degrees of success, but despite some misgivings, the surgeons at Peter Bent Brigham Hospital in Boston decided to go ahead and treat their transplant patients with radiation. Joseph Murray planned to use Xrays to suppress his patients' immune system before conducting a transplant. This would, in theory, avoid rejection and allow the transplant to 'take'. Their patients had nothing to lose – they were going to die anyway – so any new idea was worth a try.
The first patient was thirty-one-year-old Gladys Loman. A mother of two, she had been born with only one kidney. When it became infected it was accidentally removed in an emergency operation. The surgeon responsible thought he was removing a diseased appendix. This left Loman with no kidney at all and only weeks to live. She was referred to Joseph Murray, who gave her dialysis to keep her alive. This, he warned her, could be used only a few times. After that she would either die or he could attempt his experimental new procedure.
Gladys Loman lay on a mattress beneath the X-ray machine. She was curled up in a foetal position to expose her immune system to the radiation. The X-rays would destroy the white cells in her spleen, lymph nodes and bone marrow. Radiation would wipe out her body's defences and leave her completely vulnerable to the slightest infection. The surgeons turned on the machine and left the room for their own safety. Gladys lay on the mattress for three hours trying not to move. Above her the X-ray tubes bombarded her with massive amounts of radiation.
Following the procedure he had adopted with Richard and Ronald Herrick, Murray transplanted a healthy kidney into Gladys. The kidney had been taken from a stranger and would normally have been used by researchers at the hospital who were studying polio. Gladys's new kidney was completely alien to her body. The question was, now that her immune system had been destroyed, would she accept the new organ?
To avoid the risk of infection, Gladys was housed in a completely clean room – actually a converted operating theatre. When anyone came to see her they had to scrub their hands and wear operating gowns, hats, masks and gloves. She couldn't leave – she was trapped in this sterile hospital prison.
At first the new kidney failed to work, but eventually, after two weeks, it started to produce urine. It looked like the operation had been a success, so the surgeons gave Gladys a bone marrow transplant to try to give her immune system a boost. But her body had had enough. Thirty days after the transplant operation she was dead.
Gladys had endured dialysis, major surgery and massive doses of radiation. She had coped with pain and discomfort, and spent a month isolated from the world in an operating theatre. All that for a few extra days of life. You have to wonder whether it was worth it.
Staff at the hospital were becoming more and more despondent, and one surgeon quit altogether. Despite his own misgivings, Murray still believed the immune system could be overcome, and pressed on with the total irradiation procedure for eleven more patients.
By the third patient, twenty-six-year-old John Riteris, the surgical team had refined the procedure. Instead of administering the radiation in a single large dose, they used the X-ray treatments in shorter bursts. They studied cases of people involved in nuclear accidents and looked again at data from animal experiments. With Riteris, it helped that the kidney donor was the patient's brother; they were twins, but not identical twins. Their differences were revealed when a skin graft between them was rejected. Nevertheless, the surgeons reckoned that they still might have a better chance of success.
Riteris's new kidney worked almost immediately. Although his white blood cell count was alarmingly low, he managed to remain free of infection. Better still, it looked like the organ wasn't being rejected. Over the next few months he was given further doses of radiation, as well as anti-inflammatory drugs. Eventually, he left hospital with a working kidney and went on to lead a normal, healthy life. At last the surgeons had broken another barrier – they had shown it was possible to transplant organs between non-identical brothers.
But any triumph was short-lived. All the remaining transplant patients who received total body irradiation treatments at the hospital died. Radiation suppressed the immune system, but in doing so it laid the patients wide open to infection. It was the infection that killed them. The atomic dream was over. Surgeons needed to look for something else.
THE MAGIC MUSHROOM
Cambridge, England, 1976
* * *
The odds on surviving a transplant operation were improving every year, but they still weren't great. By 1965 around four out of five transplant operations were successful if the donor and recipient were related. If they weren't related, the odds fell to around one in two. In the UK in the early 1960s one of the world's most experienced transplant surgeons had conducted a series of fourteen kidney transplant operations. Only one patient survived.
There had, however, been a number of innovations during the 1960s that made transplants more likely to succeed. Surgeons were now able to match the immune systems of the donor and recipient more closely. This process, known as tissue typing, greatly improved the odds on the transplanted organ being accepted. And, with total body irradiation abandoned, scientists had developed new drugs to help combat the immune system's defences. Still, going into hospital for a transplant operation could be a grim experience, especially for children. A nine-year-old girl admitted to the Royal Infirmary in Edinburgh in 1967 later described how she was kept in isolation to avoid the risk of infection. For the five weeks following her kidney transplant operation, the only people she came into contact with were masked nurses and doctors, who had to scrub and shower before entering and leaving her room. The girl's parents were barred from entering, and could only communicate with her through a window.*
* Fortunately, the discomfort was worth it. The girl's kidney was still working more than thirty years later.
As for the new drugs, they came with a substantial health warning and a list of side effects that ran to a small dictionary. They might suppress the immune system, but the A–Z of nasty things these drugs could also do to the body ranged from the inconvenient to the fatal: from alopecia to tremor, anaemia to ulcers, cancer (through heart disease and nausea) to osteoporosis. A common side effect of, for instance, the steroids being prescribed, was facial swelling – a syndrome known as 'moon face'.
Even with the drugs and the tough procedures to keep patients isolated from infection, too many transplant patients were dying. But this didn't stop surgeons trying new and daring operations. By 1970 they had moved on from transplanting kidneys to livers and the pancreas. They had even transplanted a
human heart (see Chapter 2). But organ transplants were increasingly perceived as the last desperate measure of an increasingly desperate branch of surgery. Many hospitals refused to carry out transplants – it hardly helped their mortality figures. Murray later described the period at the end of the 1960s as 'transplantation's darkest hour'.
Then surgeons had a stroke of luck. Jean Borel, a young researcher at the Swiss drug company Sandoz, was given the task of examining a bag of Norwegian soil. The soil had been gathered during an expedition to a bleak highland plateau, and it was Borel's job to see if he could find anything useful in it. After careful analysis he was rewarded with the discovery of a new type of fungus from which he extracted a chemical. They called it cyclosporine A. This was no new penicillin – cyclosporine A was useless at killing bacteria – but it did appear to have a dramatic effect on the immune system. Borel found that cyclosporine suppressed the function of the T cells (specifically the helper T cells), preventing the immune system from attacking alien tissue.
In 1976 Borel attended an English surgical conference to report his findings. When the transplant surgeon Roy Calne heard about the remarkable new substance Borel had discovered, he couldn't wait to get his hands on it. Calne had been one of the pioneers of transplant surgery, and among the first to use drugs to suppress the immune system. He had teamed up with Murray in the 1960s and had been instrumental in improving the success of organ transplants. Now Calne wanted the opportunity to try cyclosporine. Could this drug finally provide the breakthrough surgeons so desperately needed?
Calne persuaded Sandoz to send him a sample of cyclosporine so that he could try some experiments for himself. But when the sample turned up there was a major snag: it was in its purest form – as a white powder – and the researchers in Calne's Cambridge laboratory couldn't get it to dissolve. Neither water nor any of the other common solvents they had lying around the lab worked. This meant that if cyclosporine was made into a pill, it wouldn't be absorbed in the gut. As a drug, it was all but useless. Sprinkling some white powder on the transplanted tissue to see what happened wasn't really an option. In the end the future of transplantation surgery was saved by a protective mother. Alkis Kostakis's mother to be precise.
Blood and Guts Page 17
