Another surgeon and researcher, Gilbert Campbell, tried a similar experiment with the lungs of a dog. After a successful trial during a routine operation (not on the heart) he recruited Lillehei as lead surgeon to give it a go during a tetralogy of Fallot case. The patient died shortly after the operation, but later attempts were more successful, most famously in an operation on Calvin Richmond, a thirteen-year-old Afro-American boy from Arkansas who had been badly injured in a road accident and was seriously ill. Doctors concluded that he was suffering from a hole in the heart, but there was little they could do. His only hope lay in the miracle surgery being conducted by Walter Lillehei at University Hospital, Minneapolis.
A fund-raising campaign involving a Little Rock newspaper and TV station raised enough money to send Calvin to Minnesota for treatment and he was flown north courtesy of the Arkansas Air National Guard. However, on learning of cross-circulation, the boy's mother declined to participate in the operation. A volunteer was sought from the local prison instead. When none came forward – for fear of their 'white' blood and Calvin's 'black' blood mixing – Lillehei decided to use the dog-lung method. The operation went without a hitch, the animal lung oxygenated Calvin's blood while the boy's damaged heart was repaired. The success was widely reported, although most correspondents skated over the bit about the lungs from the dead dog.
If cross-circulation had its faults – and its potential to leave both participants dead was a downright terrifying one – then employing monkey and dog lungs was hardly any better. Lillehei used the dog-lung technique a few times more, but concluded that it was far from ideal. At least Lillehei knew when to stop. As for the monkey lungs, you can only have great sympathy for the desperate parents who put their trust in William T. Mustard. Something better was needed. And while the surgeons in Minneapolis were using other humans or animals to oxygenate the blood, surgeons elsewhere were turning to machines.
DR GIBBON'S REMARKABLE INVENTION
Philadelphia Jefferson Hospital, 6 May 1953
* * *
The operation was going well. Eighteen-year-old Cecelia Bavolek lay on the table, her chest cut open to expose her beating heart. Dr John H. Gibbon Jr was relieved that the diagnosis had proved correct – Cecelia was suffering from an atrial septal defect – a hole in the heart between the two atria. His blood-splattered hands began to stitch the two sides of the one-inch hole together. For Gibbon this was a well-practised procedure, though all his previous successes had been on cats and dogs. His first, and until now only, attempt on a human patient had ended in death on the operating table.
Gibbon worked slowly, methodically and precisely. As usual, the operating theatre was crowded. There were other surgeons huddled around the table, plus assistants and scrub nurses to pass instruments. The anaesthetist monitored the girl's blood pressure; an assistant passed the surgeon some scissors. Gibbon was not relying on hypothermia to cool his patient; neither was he using cross-circulation or some other animal's lungs to pump and oxygenate the girl's blood. He was trying out the latest version of his great invention – the heart-lung machine – which was gurgling, humming and clunking beside him.
Gibbon's heart-lung machine looked (and sounded) like something out of a 1950s B movie, where the unhinged scientist meddles with forces he doesn't fully understand. But, on the face of it, there was nothing even slightly eccentric about Gibbon. He had a reputation for calm professionalism; he was well respected by his colleagues and, remarkably for a heart surgeon, was shy and selfeffacing. Colleagues described him as a 'perfect gentleman', kind and considerate. If there was anything eccentric about Gibbon, it was his obsession with developing a machine to keep a human being alive during major surgery.
Gibbon had been working on the project since the 1930s. The early attempts were crude mechanical affairs, the size of a grand piano. Visitors invited to his lab to see the machine in action were issued with wellington boots. The giant machine needed buckets of blood to get it started, but once under way could sustain the life of a very small cat. Pretty soon the visitors would notice that the floor was getting wet and that they were walking around in blood. 'Uh oh,' said Gibbon, as pints of cats' blood sloshed across the floor. 'We've got a leak again this morning.'
Emulating the human heart and lungs within a machine proved to be a tough challenge. Replacing the heart itself was relatively simple: this could be done with a pump. As long as the circuit had some pressure controls and there was a safeguard against air getting into the system, an artificial heart pump could employ off-the-shelf technology (such as the dairy pump Lillehei used for his crosscirculation operations). The problem was the lungs.
Human lungs consist of a branched network of tubes, where gases are exchanged between the air and the blood. Oxygen from the air passes into the blood, and carbon dioxide passes from the blood into the air. The total surface area available for this exchange is an astounding 84 square yards – about the same area as a tennis court. Any machine needed either to include a similarly massive surface area (much bigger than your average operating theatre) or find some other way of getting oxygen into the blood. The obvious way was to bubble the oxygen into the liquid, but this was fraught with difficulties. If even the slightest single tiny bubble remained and was allowed to pass back into the patient's bloodstream, it could kill them. Gibbon favoured pumping the blood over a flat surface – a plate or screen – to expose a film of blood to oxygen. As long as he could keep the blood flowing, this method seemed to work. The trouble came when the blood started to clot.
Over the years Gibbon's heart-lung machine became more refined. After the war the International Business Machine Corporation (IBM) offered its support and an engineer. Electronics were introduced to control the flow of blood and monitor the pressure and oxygenation process. The experimental animals got bigger and bigger, while the machine became smaller and more efficient. Even so, the heart-lung machine was still bulky and incredibly complex. Around the size and shape of two large top-loading washing machines bolted together, the contraption was so big that when it arrived at the hospital it had to be winched in through a window. But with IBM's help, it no longer resembled a crude Heath Robinson affair. Now it looked more like cutting-edge technology.
The machine was covered in switches, pipes and dials. Dials to measure acidity and pressure; electronics to monitor and control the flow of blood; even a back-up battery should there be a power failure. The top was a mass of plastic tubing, the sides hung with glass bottles. Rising from the upper surface was a rack of screens down which the film of blood would cascade to be exposed to oxygen. Snaking from it were two tubes – an input tube that would take blood from the patient's veins, and an output tube that would return oxygenated blood to the patient's body. Once it was hooked up, the machine would take the place of the patient's heart and lungs.
It is twenty-six minutes into the operation and Cecelia Bavolek is doing well. Blood that would normally pass through her heart and lungs is being diverted into the machine. It is being oxygenated and returned to her body. But something has gone wrong. The blood on the oxygenator screens is no longer running freely. It has started to clot. The pumps keep working and the pressure in the machine starts to build. On the operating table Cecelia is no longer receiving enough oxygen. The machine begins to foam. It is going to explode.
Vic Greco is responsible for the machine.* He has been working in the research lab with Gibbon and guesses what has gone wrong. Before it is hooked up to the patient the machine has to be 'primed' with blood. When they had done this earlier in the day, they had probably not added enough of the blood-thinning chemical heparin. But there is no time to analyse why it has gone wrong. They have to solve what is rapidly turning into a very messy crisis. Unless they can fix the machine, Cecelia Bavolek is going to die.
* The machine was usually the responsibility of Jo-Anne Corothers, but it had been decided that it would be 'better for the historical record' if a doctor ran the machine that day.
At
the operating table Gibbon tries his best not to get too distracted. He works as quickly as he can, but the foaming is getting worse. The blood is beginning to back up around Cecelia's body, and her circulation is coming to a halt. Greco climbs up a stepladder to hold down the lid of the oxygenator to prevent Cecelia's blood from spraying around the room. Then Bernard Miller, who has been intimately involved in the technical development of the machine, starts rerouting the pipes. He figures that the only chance they have is to bypass the now useless oxygenating screens and turn the heart-lung machine into just a heart machine. This will at least get the blood moving and restart Cecelia's circulation.
The blood starts to flow again, only this time it is not getting any oxygen. This is circulation of sorts, but what hope does Cecelia have without any means of getting oxygen into her system? Gibbon carries on anyway. Cecelia's heart loses its rhythm and goes into fibrillation. Gibbon begins to stitch together the incision he has made. He uses an electric shock to get her heart beating again and it goes into a normal rhythm. She could yet live. At least nothing else can go wrong. But it isn't Gibbon's day. As the surgeon continues to work, Cecelia starts to come round from the anaesthetic. She struggles on the operating table. Gibbon closes her chest and puts the final stitches in her skin. Remarkably, her heart continues to beat; her breathing is normal. Within a fortnight, Cecelia Bavolek is discharged from hospital, the hole in her heart successfully closed.
The operation had lasted forty-five minutes. For twenty-six of those minutes her life had been sustained by a machine. It was proclaimed an 'historic operation'; the twenty-six minutes 'the most significant in the history of surgery'. Gibbon shied away from the publicity the operation generated, shunned the press and only grudgingly gave a few quotes to Time magazine (although he declined to be photographed with the machine). As far as Gibbon was concerned, the successful operation was the result of more than twenty years of research, and he had proved that a heart-lung machine could work.
Nevertheless, Cecelia's operation was a close-run thing – she was lucky to be alive. Just how lucky would soon become clear. Gibbon attempted two more operations using the heart-lung machine. Both operations were carried out on five-year-old girls. Each of them died in the operating theatre. Gibbon had had enough. He did not have the resilience of some of his colleagues to carry on regardless. Three of his four patients had died while connected to the machine. The surgeon decided not to operate with his machine again, and ordered a year-long moratorium on its use. Gibbon never returned to cardiac surgery.
But others believed that Gibbon was on to something. At the Mayo Clinic in Rochester, less than an hour and a half's drive away from where Lillehei was developing cross-circulation, another surgeon began work on refining Gibbon's machine. After two years of research, on 22 March 1955, John W. Kirklin was ready to operate. He decided to test the machine on eight patients – no more, no less. During the first operation on a five-year-old girl, the machine practically exploded. There was blood everywhere, but the patient survived. By May Kirklin had operated on his target of eight patients. Four survived. The odds were improving, although patients still had only a fifty-fifty chance of coming out of the operating theatre alive.
DR LILLEHEI RISES TO THE CHALLENGE
Minneapolis, 1955
* * *
Back in Minneapolis, Walter Lillehei was also working on a heartlung machine, only his was a good deal simpler. Lillehei decided to try just the sort of system that everyone else had warned against – one that bubbled oxygen into the blood. He assigned the task of designing the new machine to Dick DeWall, a young doctor who had come to Lillehei with a design for an artificial heart valve – something DeWall had been working on in the evenings at home (as you do). Lillehei decided not to mention to DeWall that everyone else believed that a 'bubble oxygenator' was impossible, if not downright dangerous. But then they had said the same about cross-circulation.
Bubbling oxygen into the blood is relatively easy. The problem comes with getting the bubbles out again. DeWall set to work with a couple of pumps (the same sort of dairy pumps that were being used for cross-circulation) and some plastic tubing, all held together with a few bits of tape and some metal hose-clips. The resulting machine looked too simple to be effective, but that simplicity was the beauty of the system. The blood from the patient's veins was pumped into a mixing chamber, where oxygen was bubbled through a large rubber stopper with hypodermic needles sticking out of it. The newly oxygenated bright red blood then passed through what DeWall termed a 'de-bubbler tube' – a diagonal piece of pipe filled with an anti-foam chemical to break up the surface of any bubbles. It was the same chemical used in factories to make mayonnaise. Finally, the blood flowed down a helical spiral. This was probably the cleverest bit and was designed to defeat any lingering bubbles. The heavier blood that was free of bubbles rolled downwards with gravity, while the lighter blood, containing bubbles of air, was forced back to the top. Finally, the blood flowed out of the helix through another dairy pump and back into the patient's arteries. The whole arrangement of pumps, bottles and tubes sat on a trolley beside the operating table. When the operation was finished the plastic tubes could be thrown away – no need for the complicated cleaning or difficult preparation of the Gibbon machine.
The Lillehei-DeWall bubble oxygenator was first put to the test on 13 May 1955. Unfortunately, the patient later died, but this did not appear to be down to any fault in the machine. There were so many other things that could go wrong with this pioneering surgery. By December one hundred operations had been performed using the machine. Most of the patients survived. The odds of open-heart surgery were improving. The machine was refined, improved and commercialized. Soon any hospital in the world could purchase one.
With the heart-lung machine, surgeons were able to operate on an open heart free of blood. They could take their time and see exactly what they were doing. However, one last problem remained: even with the heart-lung machine connected, the patient's heart kept beating. Placing precise stitches into a beating heart was difficult, and the slightest slip could end in disaster. What surgeons needed was some way to stop the heart beating altogether. Of course, the other thing surgeons had to be able to do was start it up again.
The answer came from a British surgeon, Denis Melrose,* who published his research in the Lancet in 1955. He devised an injection of potassium citrate. He later changed this to potassium chloride, a compound that disrupts the electrical signals in the heart. It's the same chemical that forms the basis of the 'lethal injection' used to administer the death penalty in some US states. When it was first tried out in Britain on a patient at Hammersmith Hospital in London, they had to consult a coroner and church leaders because technically, for the duration of the operation, the patient was dead. As for starting the heart again, this was done with electricity applied directly to the heart muscle.
* Melrose was a remarkable surgeon. As well as his work on stopping the heart, he also developed a heart-lung machine, which was adopted by hospitals all over the world.
Within the space of a few years, cardiac surgery had been transformed. From Harken's first quick incision into a beating human heart to remove a bullet, surgeons such as Melrose and Lillehei were stopping hearts altogether to open them up and correct major defects. With the ability to stop the heart came even more daring and intricate procedures. Patches were stitched across large holes; artificial heart valves were grafted on; arteries were replaced with synthetic tubing. Every year more and more patients were undergoing openheart surgery, and every year more and more were surviving.
In 1958 the personable young Melrose made history by conducting open-heart surgery live on Californian television. The broadcast started at 7 p.m. when Melrose began operating on 'Tommy', the seven-year-old son of an American war veteran. For over four hours viewers were glued to their small black and white TVs as Melrose cut open the boy's heart. It was the highest-rated programme that night – real life drama with the genuine risk
that the boy might die on live television. Tommy survived, but his heart was repairable. What about those hearts that were so badly damaged that no amount of surgery could fix them? Could the heart – the centre of the soul, the very core of the body – be replaced with another one?
THE NIGHT OF THE PIGS
National Heart Hospital, London, 1969
* * *
It was a desperate, last-ditch attempt to save a life. An experimental procedure to keep a dying patient alive.
One of the UK's leading cardiac surgeons, Donald Longmore, had put in the call. The farmer assured him that the pigs were on their way. He would deliver them himself in his Land Rover. It wouldn't take long. Everything else was ready.
In the operating theatre the male patient lay on the operating table, his chest open and tubes snaking across to the bulky heartlung machine. Dark red blood flowed one way, bright crimson blood flowed back. The machine's regular beating rhythm was keeping the man alive. The anaesthetist, sitting beside a complex rack of gas canisters, calmly monitored the patient. A nurse placed some freshly sterilized instruments on the trolley; another kept an eye on the machine. All the lights and dials seemed to be indicating everything was OK. There was little else for the surgeons to do than wait. For the pigs.
They had decided to call this the 'piggyback' operation. The surgeons' plan was to graft a pig's heart and lungs into a patient so that the animal's organs would help keep the man alive. The operation had been conceived to help someone with serious heart disease. The pig's heart and lungs would work – or piggyback – alongside the patient's own heart and lungs to relieve some of the strain. At the very least it might keep this seriously ill man going for a few more months before the heart transplants pioneered in 1967 and 1968 were perfected and a suitable donor found. It might last even longer. It could even be another 'miracle breakthrough' the newspapers were so fond of reporting. As usual, the procedure had been tried on other animals and it seemed to work. The patient was seriously ill, his heart ailing. This experimental operation offered the only chance of survival.
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