Blood and Guts

by Richard Hollingham

  A small amount of the substance was extracted and injected into some guinea pigs. The animals were then cooled down to low temperatures – much lower than they had previously been able to endure. There were no ill effects. This could finally be it. There was great excitement among the team. A vial of the new chemical was personally delivered to the National Research Council in Ottawa for further tests. It was even given a name: Hibernin.*

  * Its full chemical name was 1-butyl, 2-butoxy-carbonyl-methyl-phthalate.

  The hospital appointed the finest patent lawyer, and Bigelow filed a patent (no Minnesota surgeon was going to get his hands on the product of his research this time). NASA made enquiries – perhaps they could use this substance for astronauts on long-duration space missions? A few journalists got wind that something was going on, but the researchers kept their silence. One of them even delayed a promising job offer so that he could spend more time with groundhogs.

  They decided to try out Hibernin on patients. After all, the guinea pigs had survived. The surgeons operated on two people suffering from holes in the heart. The human guinea pigs were hooked up to some tubing to enable Hibernin to be injected. Bigelow found he could cool the patients down to around 18°C – four degrees lower than anything they had achieved before – which bought the surgeons much more time. Both operations were successful. The only peculiar thing they noticed happened after the operation: the patients were sleeping for much longer than usual. They seemed groggy. It was strange, but the nurses in the recovery room said it was almost as if they were drunk.

  Now that Hibernin had been proved to work there was immense pressure to publish the results of the trial. Everyone was lined up for a major media event to make the big announcement. This would be a significant achievement for Canadian science. Then Bigelow received a letter from the patent office in Washington DC. The letter said that the chemical had already been patented. 'Hibernin' had been used for some twenty years as a plasticizer – employed to make intravenous plastic tubes pliable. Bigelow was incensed. How annoying that a biological extract from groundhogs turned out to be the same stuff as an industrial chemical. Still, the team had better do one final check as a scientific formality. Some clean plastic tubing was cut up and placed in water. A few hours later the scientists analysed the water. They extracted Hibernin.

  Rather than having extracted a miracle substance from groundhog fat, the surgeons had simply flushed out the plasticizer from the tubing used in their research. The plasticizer was a potent form of alcohol. This explained why the patients acted as if they were drunk – they were. It says a lot about Bigelow and his management style that he and his team were able to laugh about it. Ten years of visiting the groundhog farm in the bitter winter. Ten years of groundhog bites. Ten years of hard research work. Thank heavens they had held back on the publication.

  They never did find the secret of hibernation. The groundhog farm was shut down and the researchers moved on to other things. Bigelow would often cite the experience as a humbling example of 'intellectual humility'. However, the research did not go completely to waste. It opened up a whole new area of study into the use of alcohol in hypothermia. It turns out that alcohol dilates the blood vessels, allowing smoother cooling and causing less long-term damage. A refinement of Bigelow's hypothermia technique is still being used in operating theatres today.

  DR LILLEHEI HAS AN INTERESTING PROPOSAL

  * * *

  'Breakthrough' is one of the most overused words in science and medicine. Most progress is incremental – small changes in procedures or techniques, refinements of treatments and technologies. However, when it came to surgery of the heart, the only way to progress was through daring new breakthroughs: Hill sewed up a wounded heart; Harken cut into a beating heart; now Lewis had performed the first successful open-heart surgery. These surgeons had the courage to try completely new ideas on real living patients.

  Hypothermia was undoubtedly a major breakthrough, allowing surgeons genuinely to cure some of the worst heart defects. But hypothermia was severely limited by time. Doctors had only a few minutes to clamp off the heart, open it up, fix the defect, close the heart and restart the circulation. Hypothermia increased the time they had, but it could not stop the clock altogether. And when it came to open-heart surgery, there were so many things that could go wrong. There could be a problem with the anaesthetic, or a difficulty during the cooling of the patient. The surgeon might accidentally sew through a hidden nerve, interrupting the heartbeat or even stopping it altogether (this was known as 'heart-block').

  What these pioneering surgeons feared most was a misdiagnosis. Jacqueline Johnson, the first open-heart patient, was suffering from an ASD (atrial septal defect). This was a hole between the upper two chambers of the heart, the atria. Patients could also have holes between the two ventricles – a much more serious condition – or worse. There could be defects in valves, in muscle or nerves. There were some heart defects that many surgeons thought might never be conquered, not least the sinister-sounding tetralogy of Fallot.* This disorder involves not only a hole between the ventricles, but obstructions between the right ventricle and the lungs, a thickening of the right side of the heart and a distortion in the aorta, the main artery from the heart.

  * The peculiar name for this congenital condition comes from Etienne-Louis Fallot, a Marseilles surgeon who first described it in 1884.

  In the 1950s surgeons had a limited number of tools at their disposal to work out what was wrong. They could X-ray the heart, listen to the heartbeat and study the rhythm on an electrocardiograph. Usually they got the diagnosis right, but sometimes it was wrong. They would open up the heart to find a larger hole than they expected, two holes instead of one, or multiple problems. And however quickly they worked and however brilliant their technique, the surgeons would run out of time. If that happened, the patients – invariably children – died on the operating table.

  Hypothermia slowed the clock down, but surgeons now wanted to stop it altogether. To fix some of these more complex problems they needed to be able to isolate the heart completely. They needed some way of clamping off the circulation without jeopardizing the rest of the body by shutting off its blood (and hence oxygen) supply. Back at the University of Minnesota, surgeon, and now associate professor, Walter Lillehei had a brilliantly simple, if somewhat bizarre, idea. Why not keep the patient's blood circulating with someone else's heart?

  The theory went like this: as well as the patient, a healthy person would be brought into the operating theatre. Arterial blood from the healthy person's body would be pumped across to the patient. This oxygenated blood would be passed directly into the patient's arteries to circulate around his body. Then, instead of returning the blood to the patient's heart, deoxygenated blood would be returned to the donor. The concept became known as cross-circulation and held enormous promise. During the period the two people were connected, their blood mingling together, surgeons would be free to open up the patient's heart. They then had plenty of time to fix any major defect.

  The healthy donor would obviously need to have a matching blood group. But as the donor would usually be a close family member – ideally a parent – this would not be a problem. And what parent wouldn't do all they could to help their dying child? Yes, OK, it was risky taking a perfectly healthy adult into an operating theatre, sedating them and hooking them up to someone else, but wasn't it a risk worth taking? What could possibly go wrong?

  Lillehei was not one to shy away from risk – particularly when the reward was so great. If this worked, he would be able to save any number of children from an early death. He began experimenting on animals to refine the technique. He acquired a pump – normally used in the dairy industry to move milk – and some plastic tubing designed for beer taps. He had to work out the layout of the operating theatre, the staffing and procedures for two patients. Above all, he had to make sure that the system he devised to connect the two patients was airtight. Any foaming from the pump, in fac
t just one tiny bubble, was enough to induce a stroke. It could leave the patient or the donor with permanent brain damage. If something went awry during the operation, one or both of them could be killed. Lillehei had invented the first surgical procedure with the potential for 200 per cent mortality.

  SO MUCH FOR THE THEORY

  University Hospital, Minneapolis, 31 August 1954

  * * *

  Howard Holtz was an ordinary man with an ordinary job. He spent most of his working life outside, maintaining the Minnesota highways. The twenty-nine-year-old was married with three perfectly healthy children, and another on the way. There was nothing particularly unusual about Howard Holtz. Except his blood. He had AB negative blood – the rarest of blood groups, found in only 1 per cent of the population. The blood was on a donor register. Of course, it's one thing to donate blood, quite another to donate your entire circulation, but this is precisely what Howard was asked to do when he was approached to act as a donor for one of Lillehei's operations.

  Lillehei had been performing cross-circulation operations since March, and the procedure was reasonably well established, even though the risk was still considerable. The first operation on a sickly one-year-old baby boy had been successful. The patient and donor were connected for some nineteen minutes. Unfortunately, the boy died eleven days later from another complication.

  In April the surgeon had operated on a three-year-old boy and four-year-old girl. Both operations were successful – successes that the proud showman Lillehei revealed to a press conference a week or so later. He even wheeled out the cute little girl so that she could be photographed with her parents, and her father, the donor, could be questioned by the pressmen. They were told how close the poor girl was to dying, the pneumonia she suffered from, and the oxygen tent she once had to live in. Now she could grow up to lead a normal and healthy life (and she would).

  The papers described cross-circulation variously as 'miraculous', 'daring' or even 'impossible'. Some patients died, but those cases didn't get reported. There were no official mortality figures. In 1954 cross-circulation was the best chance many extremely sick children had of surviving into adulthood. Whether to go ahead with the operation was an awful decision for parents to make, but, after careful consideration, most decided it was their child's best hope. As Minneapolis was the only place in the world where this operation was being performed, most parents considered themselves lucky even to have the opportunity.

  For Mike Shaw's parents, Lillehei offered the chance of a miracle cure. Ten-year-old Mike was seriously ill. He had been diagnosed as suffering from tetralogy of Fallot and had been in and out of hospital since birth. You could tell he was sick just by looking at him. The boy was thin and pale, his skin so tinged with blue that he was practically translucent. His ears stuck out from his wan face, giving him an emaciated appearance. Mike could walk only a few paces before becoming breathless. Without surgery he had only months to live. Lillehei might be able to save his life.

  Mike's parents agreed that Lillehei should go ahead with a cross-circulation operation. They were aware of the risks, but trusted the surgeon, who was at least honest about their son's chances (although as this was the first attempt to correct tetralogy of Fallot, no one really knew for sure). The boy's blood was tested so that they could decide which family member would make the best donor, but then they hit the snag. With AB negative blood, neither Mike's parents, nor seemingly any other relatives, matched. Would a complete stranger be prepared to help?

  When Lillehei explained the situation to Howard Holtz, the highway worker agreed to lend his body to the procedure. A complete stranger to Mike Shaw, Howard figured that if his own kids were sick, someone would do the same thing for him. A child's life was at stake, and Howard realized that a 'no' from him amounted to a death sentence for Mike. As far as the safety of the operation was concerned, none of the previous donors appeared to have suffered any ill effects. Any risks (and Lillehei had explained clearly that there were risks) were surely worth taking. Howard met Mike and the boy's family. The operation was scheduled.

  Because cross-circulation involved two patients, it required two teams of surgeons. It is incredible that so many could fit into the small operating theatre. The room seems to be teeming with people, with little space between them. Everyone is gowned and masked, all slightly anxious. On the left lies the heart patient. At his head the anaesthetist and his assistant. They need to keep the patient's lungs replenished with air until the cross-circulation is connected; after that they are unusually powerless. A low curtain separates the anaesthetist from Lillehei and his assistants.

  Even with his hat and mask on, it is easy to spot Lillehei. A long scar runs down his neck and disappears beneath his gown. The scar is evidence of major surgery to remove a tumour, and gives his head a lopsided appearance. Above the table a set of lights is angled downwards, but Lillehei also wears a head lamp on his forehead so that he can see clearly into the bloody hole in the boy's chest. The lamp, which is plugged into a socket in the floor, looks like it has been cobbled together from an old desk light, and becomes uncomfortably hot above the surgeon's face.

  To the right of the main operating table lies Howard. He has also been put to sleep. This is not strictly necessary for the operation, but avoids any distress (or even boredom) on the donor's part. It is important to keep the anaesthetic as light as possible – any drug circulating in Howard's body will also circulate in Mike's. The anaesthetist also makes sure the donor's breathing is regular. As long as the two patients are connected, Howard is breathing for two. A surgeon has made an incision in Howard's right leg (left as you look at him) and inserted a tube into his femoral artery. Another tube enters the main vein in the leg – the great saphenous vein.

  Between the two operating tables snake the beer tubes full of blood. Brightly coloured oxygenated blood flows one way across the operating theatre and darker venous blood flows back the other. The blood passes through the dairy pumps to regulate the pressure and make sure the boy's fragile circulation is not overloaded. The pumps make a smooth, rhythmic sound as a line of small mechanical fingers press the blood along the tubes. Nurses move between the two patients, a surgeon monitors the flow of blood, Lillehei cuts away at Mike Shaw's heart.

  For those observing through the windows of the gallery above – even the most experienced of surgeons – this is a remarkable operation to witness. Probably the most daring, ambitious and perhaps downright foolhardy they have ever seen undertaken. As Lillehei cuts and sews slowly, methodically beneath them, some of those watching are mentally calculating the odds on Mike Shaw and Howard Holtz both coming out of the operating theatre alive.

  The pump is switched off. Mike's heart takes up the strain. Howard is disconnected. The donor leaves hospital after a few days. Not long after, so does Mike Shaw – he is cured. It is another miracle for Lillehei's revolutionary and 'impossible' surgery.

  The operation had transformed Mike Shaw from a sickly patient to a healthy, active boy. At the time of writing, Mike and Howard are still very much alive. Mike grew up to become a musician – a bass guitarist – and, thanks to Lillehei's operation, has lived life to the full. At eighty-two, Howard is also fit and healthy, and regularly goes line dancing. Several years after leaving hospital, Mike's mother complained to Lillehei that her son was now playing in a band, staying out late at night and dating a lot of girls. Before the operation she had been worried that he couldn't do anything; now she worried he was doing too much!

  Lillehei was a hero to the patients he saved, but unfortunately not every case was so successful. Later that year he had a series of failures – complications arose or a misplaced stitch resulted in heart-block. Sitting with parents telling them the worst news possible is something few surgeons get used to but, unlike some, rather than delegate the responsibility Lillehei made it his job to talk to the parents himself. Despite his self-belief and bravado, Lillehei shared their grief. But somehow he was able to recover, ready to attemp
t another operation the following day. At one point he was close to abandoning the procedure altogether, until persuaded by his boss to keep going. In the end he performed cross-circulation operations on a total of forty-five sick children. Twenty-eight survived surgery and most went on to lead normal, healthy lives.

  It was the welfare of donors that finally brought an end to the operations. On 5 October 1954 Geraldine Thompson was hooked up to her daughter and the pump between them switched on. Lillehei began to operate, concentrating on the girl's heart. However, someone else in the operating theatre was not doing his job properly. A bubble of air had got into the system. The operation was halted, but it was too late. Mrs Thompson was left severely brain damaged. The observation that this was an operation with the potential for 200 per cent mortality had almost come true.*

  * Lillehei told Mr Thompson that the failure of the operation was due to an error. He clearly felt terrible about it and, as he held liability insurance, suggested that he sue on his wife's behalf for a reasonable amount. Unfortunately, once the lawyers got involved, a reasonable amount became millions of dollars, and the case ended up in court. The court ruled that Mrs Thompson had been fully aware of the risks, so the family ended up with nothing.

  No other surgeon in the world dared to attempt cross-circulation, although some tried ideas that seem even more absurd. At the Hospital for Sick Children in Toronto, surgeon William T. Mustard was experimenting with monkey lungs. Just before the operation, he would anaesthetize and kill several monkeys, remove their lungs and clean out the disembodied organs with antibiotics. The lungs would then be suspended in jars of pure oxygen and connected to the patient. During a series of operations on twenty-one children, only three of Mustard's patients survived.