March 2000
From a distance, there was something odd about New Zealander Clint Hallam. When he walked towards you it became obvious that one arm was longer than the other. Up close the arm was even more disturbing, verging on the grotesque. Anyone who saw his hand would remember it for ever, perhaps in their nightmares.
Hallam recalls sitting in an aircraft next to a nice old lady. They got talking. The lady recognized Hallam from somewhere, but couldn't quite place him. Then she happened to glance down at his right hand. Recoiling in shock, she pressed the call button to summon the flight attendant and asked to be moved to another seat. The lady turned to Hallam to apologize. She said she had nothing against him personally, only she couldn't bear sitting next to someone who was wearing a dead man's hand.
One of Hallam's close friends made a similar confession. Hallam could never understand why, when they met, his friend would always grasp Hallam's wrist rather than shake his hand. Hallam reckoned it was an act of kindness, to avoid any risk of injury to his limb. When he asked about it, his friend confessed to finding Hallam's hand quite horrific. He wasn't the only one. The recipient of the world's first hand transplant was beginning to realize that many people found his new hand repulsive. Now, eighteen months after the operation, even Hallam was beginning to have some doubts.
From the shoulder down, the upper part of Hallam's right arm was perfectly normal. Its skin tone matched Hallam's dark complexion and was covered in black hairs and dotted with freckles. Then, just beyond the joint of the elbow, there was a sharp division where the skin became pale and practically hairless. It was as if Hallam was wearing a long white glove. There was a bulge – a swelling – where the brown skin met the white. It was a long white glove that didn't quite fit.
The underside of Hallam's lower right arm was bruised and damaged. The skin was inflamed, raw and angry – as if he had been burnt. Beyond the wrist the hands were similarly swollen. The skin was peeling; there were ulcers and the flesh was shiny. It looked like the outer layer of skin had been stripped away. When it came to the fingers, the decay was even more pronounced. The fingertips were crusty and sore, the yellow nails gradually separating from the flaking skin underneath. Small wonder the woman on the plane chose to move to another seat.
Hallam had received his hand transplant on 23 September 1998 at the Edouard Herriot Hospital in Lyon, France. The operation took almost fourteen hours and was a brilliant technical achievement. Earl Owen led a team of some the world's most experienced transplant specialists from Australia, Britain, France and Italy. France was chosen to host the operation because of its laws on organ donation. There you have to opt out of donating your body to medicine, rather than opting in. As a result, almost everyone who dies becomes a potential donor, so many more donors are available – perfect if you are waiting for a new arm and hand.
The donated limb came from that all too frequent source of body parts – a motorcyclist. The limb was matched for blood type and tissue type, but, as it turned out, not appearance.
The surgical technique used to join together Hallam's stump and the dead motorcyclist's lower arm is known as microsurgery and is fantastically intricate. The surgeons wore powerful magnifying lenses and employed precise instruments, tiny needles and the finest of threads.
First they joined together the two bones of the forearm to hold the limb stable. Then they connected the blood supply – the arteries and veins – to keep the tissue alive. Once the blood was flowing, they stitched together the muscles and tendons and reconnected the nerves. Finally, the surgeons were able to join together the skin.
At the inevitable press conference held shortly after the operation, Owen described himself as 'very happy'. It was a moment of surgical glory. 'We all have big smiles,' he said, and gave the operation a fifty-fifty chance of long-term success. Others were equally enthusiastic. Eminent British transplant surgeon Nadey Hakim called it an 'incredibly exciting breakthrough,' adding, 'to see a man restored with an arm is tremendously satisfying'.
The new arm had to be kept immobile for a few weeks while the graft healed, but everyone was optimistic that the patient would develop the full use of his limb. Hallam himself was overjoyed. It was incredible to see fingertips at the end of his arm again. With a new hand, he had been given a new life. It was a surgical miracle.
Hallam had spent years waiting for the operation. He lost his original hand in an accident with a circular saw in 1984 while he was serving time at a prison in New Zealand.* His severed hand had been sewn back on, and although it looked OK, it had little function and was all but useless. A few years later Hallam decided to get rid of the hand altogether and opted instead for a prosthetic limb. This hadn't worked out either, and he told the BBC that he had never been able to accept having a lump of plastic attached to his arm. It was not natural. Perhaps one day the technology would be available for a hand transplant.
* The circumstances of the injury remain somewhat vague. The surgeons who carried out the 1998 transplant operation were unaware that Hallam had sustained the injury in prison. Hallam's somewhat chequered past was revealed by the media following the operation. This did little to endear Hallam to the surgical team. Owen said later that although they had conducted psychiatric tests, they should have looked more closely into Hallam's background.
However, a few months after the 1998 operation Hallam was struggling to overcome his disappointment. It wasn't just the obvious mismatch between his new arm and the old one, so much as the practicalities. The new arm did not work very well. There was only limited movement: Hallam could move the limb and bend his new fingers to a limited extent, but he said he was almost more crippled with the hand than he had been with a stump.
There was a marked contrast between Hallam's experiences and the surgeon's rhetoric. They were claiming the operation as a great success and told the media how Hallam could grab things, pick up a glass and even write with a pen. They were also pleased that he could feel pain and temperature on both sides of the new grafted hand. But they weren't the ones who had to deal with the side effects.
To avoid the transplanted limb being rejected by his body's immune system, Hallam had to take a cocktail of different drugs. There could be eleven tablets to swallow in the morning, four at lunchtime and eleven more in the evening. The exact amount varied from week to week, but Hallam was usually being prescribed some combination of steroids, anti-rejection tablets and immuno-suppressants – drugs that, as the name suggests, suppressed his immune system. He was also taking pills to help his fingernails recover. Every day he had to count out the various tablets to make sure he didn't take too many or too few. The pills were keeping his arm alive, but they were also having other effects. Hallam had started to develop diabetes and needed to take insulin to control his blood sugar. Physically, he was also changing. Hallam was used to keeping fit and had been in reasonably good shape. Now he found he was growing breasts. Worse, the powerful drugs increased his risk of developing cancer.
And it was not just the physical limitations that were taking their toll. Hallam was beginning to realize that there was a psychological price to pay for having a dead man's hand attached to his body. Aside from the mental anguish for any man of growing breasts, the transplant increasingly looked and felt like it did not belong. Other people would comment, saying how white the transplant looked, or how the new hand was smaller than the other one. Hallam realized how angry he was with the doctors for not waiting for a hand that was better matched. It was as if, he said, they were more interested in the transplant than the person. He had dreamt for years of having a new hand, but the reality was proving increasingly uncomfortable. What happened next became inevitable.
By 2001, Hallam had begun to take fewer and fewer of his prescribed drugs. Every time he got sick his immune system struggled to cope, so he decided the answer was to cut down on the immuno-suppressants, but the effect on his hand was hideous. Attacked by his own body's immune system, the limb had all but died; the flesh was rotting away on the end of Hallam's arm. He had lost all feeling; it was a wonder the infection hadn't spread to other parts of his body. Hallam told the BBC he felt 'mentally detached' from the hand. He had had enough and begged the doctors to remove it.
In February 2001 Clint Hallam's hand was amputated by Nadey Hakim, one of the surgeons who had helped attach it in the first place. The procedure, at a private London clinic, took ninety minutes. Hallam was relieved to see it gone. Some of the surgeons who had enjoyed such acclaim only a few years before were angry that their work had been in vain; that their patient had not persisted with his medication.
In retrospect, Clint Hallam was probably the wrong person to receive the world's first hand transplant. If he had done exactly what he was told – had taken his medication, had followed doctor's orders – he might still be walking around with a dead man's hand. Even so, he would have had to cope with the physical symptoms, the strict drug regime and probably a shorter lifespan as a result of diabetes or perhaps cancer. Eight years after his transplant, Hallam was once again fitted with an artificial limb. He claims he has no regrets about having the transplant; his only regret is being the first.
The case of Clint Hallam illustrates the barriers that have to be overcome for successful transplantation – whether it is the transplantation of a hand, finger, kidney or heart. The first barrier is simply one of technique. It has taken more than a century to develop the surgery of transplantation. Stitching together blood vessels is difficult enough, let alone trying to join muscles, tendons and nerves. But the operation itself is only the start. Next there is the enormous problem of rejection. The body's immune system will fight any alien tissue. Even with the latest drugs, rejection is still a major hurdle for transplant surgeons.
The final problem is more subtle, and is downplayed or ignored by surgeons at their peril. Any transplantation involves overcoming a psychological barrier. What is the effect of having a dead man's hand transplanted on to your arm? It certainly bothered that woman on the plane. Did Hallam ever think about the motorcyclist who had died? Before the transplant that hand had been gripping a motorcycle handle – an essential part of a whole different human being. What about the psychological effects of a kidney or heart transplant or even a face?
The surgeons who had operated on Clint Hallam had overcome the technical problems. Until he stopped taking them, the drugs had countered his body's physical rejection. But the surgeons had failed to overcome the final barrier. Consciously or not, it was Hallam himself who had rejected the hand.
THE DEADLY DENTIST
James Spence (and Sons), Soho, London, 1765
James Spence was always very discreet. No one, he assured the young lady, need ever know that she had visited him. Of course, nowadays he rarely conducted these procedures himself. He left most of the day-to-day work to his sons. However, for this fine lady he would make an exception. She was fearful of going to see anyone else (there were so many charlatans about these days). Spence had already established the finest reputation in London for pulling teeth, and was proud to call himself a dentist, even though 'dentistry' was only just starting to establish itself as a respectable profession. There was no one better to go to for a tooth transplant.
Spence preferred to use living donors for his tooth transplants. They were easy to come by and it avoided the repulsion many people felt at the idea of eating food with teeth from the dead. Mind you, teeth taken from cadavers were a lot cheaper, and many dentists did a roaring trade in teeth extracted from the mouths of soldiers killed on the battlefield.
Nevertheless, today Spence needed teeth from the mouths of young women. Earlier that morning he had dispatched a servant to locate suitable donors in the neighbourhood – women who would be willing to give up their front teeth. They would be handsomely rewarded (well, it would be handsome to them; the expense would make only a small dent in Spence's substantial profit margin). By mid-morning, several young women were queueing in the alley behind Spence's offices. He planned to take a few teeth, maybe a couple from each woman, to see which ones produced the best fit.
His patient arrived accompanied by a friend for support. Spence ushered the women into his consulting room. The patient sat down on one of the plush, high-backed leather chairs. At first glance she was something of a beauty and would, he thought, have no shortage of suitors. But when he took a look at her mouth he realized it was little wonder she had come to him for help. Her teeth were in a terrible state. Her mouth stank of decay, with black rotten stumps emerging from raw, inflamed gums. She was worried about the pain she was going to experience. Spence reassured her that she would hardly feel anything; he stopped himself from telling her that most of the pain would be experienced by the donors.
Rotten teeth were the price the wealthy of Georgian England paid for their lifestyle. These days everything seemed to have sugar in it – from tea at breakfast to the sweets many sucked before bedtime. All this sugar was ruining the nation's smiles. If this lady ever hoped to find a husband, something would have to be done. She could have had some false teeth made – carved for her from ivory – but these rarely fitted well. No, thought Spence, in coming to him she had made the best decision.
Across Europe tooth transplants had been carried out for many years. The surgical textbooks gave detailed accounts of how to carry out transplantation operations, with some suggesting the use of animal teeth. Ambroise Paré (see Chapter 1) was one of the many eminent surgeons who wrote about the procedure, describing the case of a noblewoman who received a tooth transplant from one of her ladies-in-waiting. By 1780, transplanting teeth from poor donors to wealthy recipients had become commonplace. There were a few voices claiming that it was morally dubious, and others who came to realize that the transplants were rarely successful, but Spence backed neither of these views.
Spence went to examine the women queuing by the back door. Some of them he dismissed straight away, including one whose face was covered in sores and another who looked like she was in need of a tooth transplant herself (not that she would ever be able to afford it). The remaining three he ushered inside so that he could take a closer look. They all appeared to be in reasonable health – no telltale signs of venereal disease or TB. Spence remained unconvinced that disease could be passed on from the donors to recipients. Still, best to be on the safe side. He explained to the three women what was going to happen and how much they would be paid for their contribution. His servant went to fetch the pliers.
Spence seated his first donor down on a couch in a back room and asked her again if she was willing to go through with the extraction. She nervously agreed. Spence took the pliers and gripped an upper left canine. With his knee placed against the couch for leverage, he pulled sharply on the tooth, twisting it until it came away. The woman screamed as blood poured from her mouth and dribbled down her chin. The servant passed her a handkerchief to plug the wound and Spence headed next door to perform the transplant.
He instructed his patient to open her mouth and try not to make a sound. She grasped her friend's hand as Spence held her jaw steady. With the pliers he extracted one of her rotten teeth and with his lancet made a slit in her gums. He gave the new tooth a quick wipe with a cloth to remove the blood and jammed it into the cavity. The patient was sobbing with the pain but did her best to keep her mouth open. Her friend reassured her that she was being brave. Spence finished off by looping a thread around the new tooth and tying it to the adjacent teeth. The first transplantation completed, Spence went back to his donors for more teeth.
After an hour or so, the donors left with a few shillings and fewer teeth, and the patient nursed a swollen jaw. Nevertheless, she was very pleased with the outcome – a glance in the mirror was all she needed to be convinced that all the pain had been worthwhile. Spence assured his patient that the swelling would soon subside and congratulated himself on another successful operation.
Within a few days the swelling had indeed subsided, although the new teeth felt a little loose. After a fortnight she started to experience sores around her mouth and a rash developed across her body. A physician was sent for, but when a large abscess began to eat away at her nose it was obvious to everyone that she was suffering from syphilis. It could only have come from the teeth; the disease must have been passed on from the donor's blood. Within a few months the whole side of her once beautiful face was horribly disfigured. It wasn't long before the poor young woman was dead. All because she had wanted some nice white teeth.
Spence is said to have infected at least seven of his wealthy patients with syphilis. But it wasn't incidents like this that finally put a stop to tooth transplantation, or the fact that almost all tooth transplants failed through rejection. What brought the practice to an end was the invention of an alternative: ceramic false teeth. However, the idea that living matter could be taken from one person to be transplanted in another was an idea that was far too good to dismiss for long.
Although Spence's forays into transplantation often ended in disaster, his reputation as a dentist attracted the attention of a young surgeon, John Hunter, a man obsessed with understanding what made something alive – the 'living principal'. It is difficult to know how best to describe Hunter. Pioneering surgeon, teacher, naturalist, philosopher – he was to become all these things. His observations and 'scientific' experiments shed new light on biological processes. He advanced the understanding of the human body, both its anatomy and physiology, and devised daring new medical and surgical techniques. His collaboration with Spence not only yielded the first accurate scientific study into teeth, it also gave Hunter far more ambitious ideas.
After witnessing tooth transplants, Hunter started dabbling with other transplantation experiments. He cut the spur from the foot of a cockerel and grafted it on to its head; he took a human tooth and transplanted it on to a cockerel's comb; he even transplanted the testes from a cockerel and attached them to a hen. In a few cases his transplantation operations appeared to be completely successful, but most of them failed. It is thought that the transplants between animals succeeded only because, through inbreeding, the chickens were genetically very similar.
Hunter showed that transplantation was possible – albeit a little hit or miss – and made the first tentative steps towards understanding it. Future generations of dentists, surgeons and scientists, including Charles Darwin and Joseph Lister, would owe Hunter an immense debt of gratitude. People would visit the museum he founded and marvel at his scientific discoveries. But while Hunter would be commemorated as a great pioneer, other surgeons who pushed the limits of science would not be so lucky.
A CAREER THAT STARTS WITH MURDER
Lyon, 25 June 1894
French president Sadi Carnot had rarely received such a rapturous welcome – not only from the mayor and city officials of Lyon (which was only to be expected), but from the exuberant crowds that filled the streets everywhere he went. During the last few days, horses draped with the flag of the republic had led his carriage to banquets held in his honour, and from a balcony he had watched a torchlight procession and a display of fireworks and illuminations. He had marvelled at the wonderful exhibits on view at the Exhibition of Arts, Sciences and Industries. Finally, after all the excitement, he was looking forward to an evening at the theatre, where a gala performance had been arranged.
The president left the Lyon Chamber of Commerce, where he was guest of honour at yet another banquet, a few minutes after nine o'clock. Thousands of spectators cheered as he crossed the short distance to his open carriage waiting outside. Everyone was trying to get close, pressing to catch a glimpse of the French leader. The president didn't mind – it was wonderful to be greeted in such a way.
As he settled into his seat and the carriage started to move off, a young man in a light brown suit and peaked cap was pressing his way through the crowd. He was clutching a newspaper in his hand, but no one took much notice of him; he was just another person jostling for the best view. Suddenly, the man jumped on to the carriage step and flung aside the newspaper to reveal a dagger. The president barely had time to react before the knife was plunged into the left side of his chest and he slumped back against the seat.
President Sadi Carnot was still alive, but unconscious. The assassin had hardly withdrawn the dagger before he was seized by the crowd, their cheers having turned within seconds to screams of horror. The man was punched to the ground amid cries that he should be killed there and then. As the police did their best to protect him from the fury of what had now become an angry mob, the carriage containing the dying president was rushing towards the hospital.
As the assassin was bundled off to the police station, protected by police and mounted guards, the president was laid on a bed. His condition was worsening. A crimson stain on his shirt was spreading as blood seeped from the wound and dripped on to the sheets. Lyon's finest surgeon was summoned. At the police station the assassin gave his name as Cesare Giovanni Santo, a twenty-two-year-old Italian anarchist with a poor grasp of French and, as one reporter put it, 'a very small moustache'.
The doctors who had now gathered around the president concluded that the dagger had missed his heart, but one of his major blood vessels 'in the region of the liver' had been punctured. The blood pouring from his wound told only part of the story: most of the blood was being lost inside the president's body.
They did their best to stem the flow with towels and bandages, and at 11.30 the surgeons issued an optimistic statement in which they stated that the condition of the president was 'alarming but not hopeless'. The bulletin went on to suggest that the haemorrhage had ceased. The surgeons were wrong. The president was bleeding to death and there was nothing anyone could do. At 12.45 the president of France was declared dead.
French justice was swift. A little over a month after the assassination the president's murderer was tried, convicted and executed. The Lyon surgeons concluded that Carnot had died from blood loss caused by a wound to the portal vein – the major blood vessel from the intestines to the liver. Even if they had attempted to operate on him, they would have had little chance of success. No one had managed to mend a broken blood vessel before; the only option open to surgeons was to tie off blood vessels completely. This was fine in a limb, although cutting off the blood supply inevitably ended in amputation. When it came to a major internal vein or artery, the procedure was out of the question.
The whole affair was deeply shocking, particularly for a young doctor at the hospital, Alexis Carrel. In his autobiography Carrel wrote how the president's life 'left him with his blood, in the midst of the holiday crowd. I can still hear it flowing drop by drop fifty years later.'* Carrel was appalled that the surgeons had been unable to save the president. The death set him on a path that would lay the foundations for modern transplant surgery. It would lead Carrel to a Nobel prize, a partnership with the world's most famous aviator, and into collaboration with the Nazis.
* It is very unlikely that Carrel was at the bedside of the dying president, but in later years he seems to have convinced himself – and everyone else – that he was. There is also some debate over exactly where the president died. Some historians claim it was at the hospital, whereas reports in newspapers of the time say it was in the city préfecture.
Alexis Carrel was an odd-looking young man. He had the countenance of someone who thought about things a lot, whether it was the death of a president, the latest surgical advances or the future of humanity. Carrel was intense, self-absorbed and somewhat distant. It was as if he were observing the world from a higher intellectual plain. Physically, he was also quite unusual. Anyone meeting him for the first time found it difficult to identify what it was about his appearance that was so unsettling, until they peered into his tiny eyes. Behind his pince-nez, which he wore for his chronic short-sightedness, you could see that one of his eyes was brown and the other one blue.
Throughout his life Carrel collected enemies, usually power ful ones. And where better to start his collection than with his superiors at the hospital in Lyon – those surgical butchers who considered themselves such experts, but who had so impotently failed to save the life of the president. They said saving him had been impossible; Carrel thought they were wrong, said as much and set out to prove it.
First he needed to develop his sewing skills, but not the brutal, clumsy sewing he was used to seeing during operations in the hospital (he sometimes wondered if surgeons took pride in the grotesque size of the scars they left behind). If Carrel wanted to sew together delicate blood vessels, he needed to learn how to do minute, delicate, precise stitching. So he headed to Lyon's silk district and acquired the services of the city's finest embroiderer, Madame Leroudier.
Carrel was a driven and conscientious pupil and, with the smallest of needles and finest silk thread, he worked tirelessly to perfect his technique. Just trying to thread the microscopic eye of an embroidery needle takes considerable patience and determination but Carrel worked night after night, much to the derision of his macho medical colleagues. Within months, he had not only mastered the stitches, but was almost as good as Madame Leroudier herself. It was said that Carrel was so proficient that he could place five hundred tiny stitches in a single piece of cigarette paper. Now all he had to do was apply his beautiful embroidery technique to some veins.
Blood vessels are circular, slippery and easily damaged. Cut one and it resembles a damp, floppy drinking straw. Clamp a vein or artery with forceps and it is left crushed and bruised; sew a vein back together again and it will almost certainly leak or clot – either way, it will be all but useless. Carrel had to overcome all these problems if he was to sew blood vessels together successfully, so he headed back to the laboratory with his tiny curved embroidery needles and fine silk thread and set to work.
The first thing he worked out was how to stop the flow of blood without damaging the vessel. Using bands of cloth, he would gently squeeze vessels shut and successfully hold back the blood. If he rolled back the edges of a cut vessels so that they resembled cuffs, he could sew the cuffs together without the usual leaks or damage that led to clots. But it was Carrel's final discovery that was his most masterful. He called it the 'triangulation method' of suture.
First, he joined the ends of the blood vessel together by placing three stitches equal distances apart around its edge. For each stitch he left a short piece of silk thread attached. The blood vessel was thus joined at three points. Now here's the clever bit: when he pulled tight on all the threads at the same time he created a straight line between each one. He had turned the circular vessel into a triangle. He could then sew along the straight lines between the threads. It was a remarkably simple idea, but extremely effective. He had overcome the problem of trying to sew around a circular vessel by doing away with the circle. Once he had sewn along the first line, he moved on to the second and the third. When he released the threads, he was left with a neat sutured join in the blood vessel. It was such a simple technique that even the surgeons he held in contempt would be able to manage it.
It was no great surprise to anyone when Carrel failed to receive promotion at the hospital in Lyon, and it was probably best for all concerned when he left for the United States to pursue his research. In Chicago he teamed up with Charles Guthrie, a similarly obsessed medical researcher, and together they improved Carrel's technique with ever finer needles and thread. They stitched severed veins and arteries, and joined the two together. Usually the veins and arteries belonged to a dog, sometimes a cat, or occasionally a guinea pig. Some animals survived the procedures, some didn't. Carrel was unsentimental about any creatures that might suffer in the name of medical progress.* Armed with his new surgical techniques, he had a much greater purpose in mind: transplantation.
* The animals would have been anaesthetized, and there is no evidence that they were mistreated. Whether the experiments themselves amounted to mistreatment is a matter for debate.
INSIDE THE LABORATORY OF ALEXIS CARREL
Rockefeller Institute for Medical Research,New York, June 1938
Dr Alexis Carrel was now considered one of the world's most eminent and famous scientists. Surgeons, politicians and celebrities came to seek his advice or expert opinion. This month he was even on the front page of Timemagazine. The reporter had been lucky to secure an interview – Carrel was usually hidden away in his laboratory, guarded by his protective secretary, as devoted to his work as ever. Since winning a Nobel prize in 1912 for his work on 'Suture of Blood Vessels and Transplantation of Organs', Carrel had conducted thousands of transplantation experiments. He had transplanted limbs from dogs, kidneys from cats and testicles from rabbits. He had taken lungs from guinea pigs, heads from dogs, ovaries from cats and thyroids from kittens (the attrition rate of kittens was particularly high). He had swapped the leg of a black dog with the leg of a white dog and replaced the head of one dog with the head of another.* He had grafted kidneys, livers and lungs; he had transplanted organs, glands and legs. He had swapped skin, rearranged veins and added hearts. No animal, it seemed, was safe from Carrel's increasingly bizarre research.
* Carrel wasn't alone. In 1954 a Russian transplant surgeon, V.P. Demikhov, went even further, transplanting the head of one dog on to the back of another to create a monstrous twoheaded creature. This disturbing experiment was brought to an end after the two heads started fighting each other.
Carrel's laboratories were every bit as sinister as the experiments. Built on the top floor of the Rockefeller Institute, they were reached from an anteroom by a narrow spiral staircase. Here Carrel's fanatical team of researchers worked in sterile windowless labs. They were lit by roof lights and electric bulbs in the plainest of shades. Everything else was in varying tones of black – from the matt black floors to the bare grey walls. Even the cloths on the operating tables were black. There was no colour, no dust and no reflections. Dracula couldn't have conceived a more suitable lair.
The outfit the scientists wore might have been designed by a fetishist. The researchers were known as the Black Gang. They worked in black gowns and black trousers. Their heads were covered in black linen balaclavas. The headgear was square in shape – like a welder's helmet – with only a narrow slit for the eyes. On their hands the scientists wore thick, black rubber gloves. These shadowy, featureless men would be the last thing most of their experimental animals ever saw.
There was a good reason for all the black. Carrel had designed the labs to minimize reflection and glare from the lights – vital, he believed, to help the researchers see what they were doing, particularly when they were working on such tiny bodies (such as those of kittens, rabbits and guinea pigs). The all-enveloping outfits were designed to minimize infection. Joseph Lister would have been proud of the lengths to which Carrel had gone to keep the place aseptically clean (see Chapter 1), although Lister might have preferred a cheerier colour. The odd thing was that the only one who wasn't dressed entirely in black was Carrel himself. He had taken to wearing a peculiar white hat that resembled a bandage stretched over his bald head.
In the late 1930s most of Carrel's laboratory was devoted to his 'perfusion' experiments. He had gone beyond simply transplanting organs to removing them altogether. His aim was to keep organs – eventually human ones – alive and functioning in a totally artificial environment. For the last three years he had been working with his close friend, Charles A. Lindbergh, the first man to fly across the Atlantic. Although it might seem an odd partnership, the celebrity aviator and eccentric French scientist had much in common. Lindbergh shared many of Carrel's political views, they were similarly driven, and both were ambitious to advance medical science.
In 1938 Carrel and Lindbergh were celebrating the publication of a book they had written together, The Culture of Organs. In it they outlined the 'cultivation' of organs using the Lindbergh pump. The pump was designed to bathe living tissue in nutrients to keep it alive, and looked exactly like the sort of thing a scientist working in a sinister black laboratory would devise. The contraption consisted of a series of pumps, bottles, gauges, valves and odd-shaped glass flasks all connected with lengths of rubber tubing.
The pump, the culmination of years of effort, was really an early type of heart-lung machine – it kept organs alive, nourishing them and providing them with oxygen. At around the same time, surgeon John Gibbon (see Chapter 2) was also developing a heart-lung machine, only his aim was to keep entire organisms alive – eventually humans – while life-saving surgery was carried out. By the late 1930s Gibbon could sustain the life of a cat. In comparison, Carrel's motives were far more scientifically detached. He was able to sustain the life of a disembodied cat's heart. Improving treatments or saving people's lives wasn't enough for him. He had far loftier ambitions.
For a start, the Lindbergh pump was to be used to study organs outside the body. It allowed Carrel to examine the nutritional requirements of a particular organ, or study the chemical processes taking place. He could assess the production of insulin in the pancreas, urine excretion in the kidneys or the life cycle of cells. With the techniques he developed, Carrel took the creation of 'cultures' of living tissue to a whole new level. On one bench in his black laboratories he grew cells taken from the heart of a chicken embryo. So far he had managed to keep successive generations of these cells alive for twenty-six years.
This was all very well, but it was only incidental to his life's work on transplants. Carrel planned to remove damaged organs from a patient's body – a diseased kidney, for instance – place the organ in the pump apparatus and treat it in this artificial medium until it healed. Once the organ had been cured, he would replace it in the patient using the techniques he had first developed in Lyon. It didn't even need to be a kidney – it could be a leg, an arm or even a brain. If Carrel's laboratory was nightmarish now, imagine what it would be like lined with bottles of bubbling glass jars filled with dismembered limbs, diseased hearts and cancerous lungs.
But even this wasn't enough for Carrel. In what he called his 'new era' of surgery he foresaw a time when human organs could be grown in the lab and used to manufacture drugs such as insulin. He never made it clear who might provide these organs, but the ethics of his work always came second to scientific progress. As the reporter from Time magazine suggested, Dr Carrel was 'looking for the fountain of abundant, replaceable age'. But probably not for everyone.
Carrel's collaboration with Lindbergh underlay a much deeper moral purpose. The two men were out to change the human race. Three years before, in 1935, Carrel had published his philosophical treatise Man, the Unknown. It was widely read and drew acclaim from scientists, statesmen and intellectuals around the world. In it Carrel outlines his views on everything from future scientific progress to the role of women in society. He was convinced that man was in a state of physical, mental and moral decline and needed to be 'remade'.
'For the first time in the history of humanity, a crumbling civilization is capable of discerning the causes of its decay,' Carrel wrote. 'For the first time, it has at its disposal the gigantic strength of science.' The recent political and economic turmoil had demonstrated the failings of democracy; he wanted to see a new social order. Countries should be run by a ruling elite, their standing in society determined by biological worth. Man had the power to transform himself, to control his genetic destiny. Only the strong should be genetically perpetuated.
The irony that a short, balding, myopic Frenchman (with different-coloured eyes) should be calling for the creation of a master race was lost on Carrel. But his call for the introduction of eugenics was well received. The idea that only the genetically 'superior' should be allowed to breed (or encouraged to breed) was something that many in power had been thinking for some years. At various times everyone from Winston Churchill to George Bernard Shaw and H.G. Wells had flirted with the philosophy of eugenics. In six American states laws had been in place for decades to allow the forced sterilization of the insane and 'mentally deficient', and in Germany Carrel's scientific standing added credibility to the philosophy of the Nazi government. In the German edition of his book, he even went so far as to endorse Nazi policies.
Carrel probably had little knowledge of what was really going on in Nazi Germany, despite having travelled and lectured there in 1936. By the mid-1930s eugenics was at the heart of German government policy. Hitler was oppressing opposition groups, people of Jewish faith, ethnic minorities, homosexuals and gypsies (among others). The government had set up concentration camps, as well as secret extermination centres where the mentally and physically disabled were being killed. At the same time women of Aryan descent were being encouraged to have as many children as possible.
However, while Carrel advocated preventing the criminal or insane from breeding, he shied away from destroying 'sickly or defective children as we do the weaklings in a litter of puppies'. Instead he felt the only way to 'obviate the disastrous predominance of the weak is to develop the strong'. Among his suggestions was the proposal to remove the sons of rich men from their families so that they could 'manifest their hereditary strength'. And although he believed childless women were 'not so well balanced', unlike many misogynists he was a firm believer that women should be highly educated, 'not in order to become doctors, lawyers or professors, but to rear their offspring to be valuable human beings'. As for his treatment of criminals, those who couldn't be conditioned with a whip should be 'humanely and economically disposed of in small euthanasic institutions supplied with proper gases'. You can see why the Nazis were so taken with his views.
Not everyone was impressed. There were rumours that 'occult practices' were taking place in Carrel's black laboratories. Even that Lindbergh was planning to have his heart removed so that it could be replaced by a mechanical device of Carrel's creation. This wasn't so far from the truth: the two men were operating in a scientific hinterland. Lindbergh was fascinated by questions of life and death, and had contemplated immortality. Carrel was a believer in clairvoyance and telepathy, and an advocate of the power of prayer (he even wrote an article about it for the Reader's Digest).
On 28 June 1938 Carrel was sixty-five years old and the strict rules of the Rockefeller Institute meant that he was forced to retire. For someone so passionate about his work, this was incredibly frustrating, but perhaps now was the time to realize his life's ambition and set up his own institute devoted to the study of man. An institute that would build on his theories outlined in Man, the Unknown. An establishment that would set mankind on a triumphant path to the future.
Carrel's opportunity came in February 1941 (some ten months before the United States entered the Second World War) when he joined a relief mission to take food and medical aid to occupied France. Quite what Carrel's motives were for joining such an endeavour is unclear, but it wasn't long before he'd offered his services to the Vichy government. He saw the downfall of France as evidence for his theories on society. France had been 'crushed because of our corruption, vanity and weakness'. Now he had the opportunity to help in 'remaking' the country.
On 17 November, despite the fact that the French economy was crippled by the German occupation and most ordinary people were on a starvation diet, Carrel was awarded a generous budget to set up his new institution. His foundation would study measures to 'safeguard, improve and develop the French population'. Offices were commandeered at the Rockefeller Foundation in Paris and, seemingly oblivious to the suffering taking place around him, the selfabsorbed little Frenchman resumed his experiments.
After Paris was liberated by the Allied forces in August 1944, no one was sure whether or not Carrel should be arrested as a collaborator. Although his work was backed by the hated Vichy authorities and endorsed by the Nazi leadership, Carrel had merely been getting on with his research. During the war he had even spoken out against the inadequate rationing imposed by the Germans, and counted members of the Resistance among his friends. Some efforts were made to detain him, following press accusations that he was a pro-Nazi racist (which was, strictly speaking, true). The American ambassador was even asked to intervene on his behalf. In the end Carrel died before anyone could decide what to do with him. Sympathetic biographers have claimed that he died of sorrow, devastated that people thought so ill of him. Within a few years his public image had gone from scientific hero to Nazi villain.*
* Charles Lindbergh almost suffered a similar fate. In 1941 he gave a speech in Iowa, during which he called for appeasement with Germany. His anti-British and anti-Semitic views were widely vilified, and many people, including Lindbergh's own mother-in-law, distanced themselves from him. After Japan attacked Pearl Harbor in December that year, Lindbergh returned to aviation, flying more than fifty combat missions in the Pacific and instructing many young pilots. However, it was several years before his reputation was sufficiently rehabilitated for him to once again be considered an American hero.
Alexis Carrel could have been a great medical hero; instead his name has been all but erased from the history books. His enormously popular text Man, the Unknown was removed from most libraries, his perfusion experiments abandoned, his laboratories shut down. Scientists and surgeons were embarrassed to have been associated with him. The press that once sang his praises no longer mentioned him. Everyone conveniently forgot that they had once thought eugenics was a good idea. It was left to a few loyal colleagues (including Charles Lindbergh) to try to put Carrel's side of the story. As a result, the biographies are deeply divided. Some are damning in their condemnation, others are obsequious in their praise. But if you try to look beyond the man to his many achievements, they are quite remarkable.
Carrel was the first doctor to work out how to sew blood vessels together. This discovery alone helped save countless lives. When arteries or veins were damaged, his efforts meant that they could be successfully repaired. His technique made transplants possible and opened up a whole new area of surgery. His pioneering experiments with tissue culture gave scientists a much greater understanding of organ and cell function. They also allowed the investigation of conditions such as diabetes. His idea that limbs and organs might be grown or repaired in the laboratory was decades ahead of its time. Advances in stem cell research might one day make this possible. As for his views on eugenics, it is hardly fair to single out Carrel as a villain. In the first half of the twentieth century his views on the future of humanity were shared by many other influential people.
However, for all his achievements and technical advances, Carrel kept coming up against a major problem. Transplants of an organ between different parts of the same animal were invariably successful, but almost every one of his hundreds of transplants between different animals ultimately ended in failure. The operations had gone well, the organs would function for a while and then, within days (or occasionally weeks), they would fail. Carrel concluded he was coming up against a biological force that he was powerless to counteract. Despite fifty years of experiments, he failed to overcome a major obstacle to successful transplantation: rejection – the body's reaction to foreign tissue. In his battle with the body's immune system, he was defeated time and time again.
The immune system is in a constant state of war and, as Carrel discovered, a transplanted organ provides an easy target. Everything alien to the body comes under attack, from transplanted tissue to bacteria, fungi and viruses. The human body employs a whole range of different cells and techniques to repel invaders, and the immune system is continuously evolving to adapt to new threats. Transplant an organ and the body will rapidly set to work to try and eliminate the foreign tissue. The immune system even has its own distribution network – the lymphatic system – and a series of lymph nodes where the various immune system cells congregate.
The white blood cells form the core of the body's immune response. Although they are called white blood cells, they are actually transparent. Every single millimetre of blood has some ten thousand white blood cells, all poised to take on invaders. The first line of defence is made up of neutrophils, which can swallow up and kill bacteria. These are backed up by the even more fearsome lymphocytes, which come in two main forms: B and T.
B and T cells are manufactured in the bone marrow, found in the long, flat bones of the body, such as the pelvis. B cells produce fragments of protein called antibodies, which bind to the surface of foreign invaders. These antibodies either disable the invader or mark them out for destruction. T cells come in two different varieties – helper T cells and killer T cells. The helpers work with the B cells to produce antibodies and also assist the development of the killer T cells. It is these killer T cells that are the really nasty ones. They target anything identified by the B cells as alien, ambush the invaders and destroy them.
Doctors know all this now, but fifty years ago the body's immune response was still shrouded in mystery. For transplant surgery to be successful, the formidable barriers of the body's own defences would have to be studied, analysed and overcome. In the meantime, some surgeons were prepared to carry on regardless.
LIFE AFTER DEATH IN FRANCE
Paris, 12 January 1951
Seven years after Alexis Carrel's death another Frenchman was about to die. He was scheduled to be executed by guillotine within the walls of the Santé prison in Paris. Not that many people cared. Ever since the abolition of public executions in 1939, interest in the death sentence had waned considerably. This was merely another routine execution of a criminal that society could probably do without.
It was a bitterly cold morning. The executioner's breath mingled with the icy morning mist and choking smog of the city. The guillotine stood in the courtyard, blocked in by the towering brick walls of the prison. What a place to die.
The killing machine itself was once considered the height of technology – a machine to end life efficiently and humanely. These days it was beginning to show its age. The plank where prisoners rested their bodies for the last time was worn, the high wooden gantry was discoloured from age, and even the bucket for catching the disembodied head was looking battered. The only part that still appeared as good as new was the glistening steel blade, sharpened the previous day.
The executioner examined the ropes on the machine and checked the straps on the plank. He positioned the bucket of sawdust where he judged the severed head would fall. With public executions it used to be embarrassing to see a head bounce from the basket and roll towards the crowd. It wasn't dignified. The least an executioner could be was professional. He pulled on the rope and hauled the heavy blade to the top of the gantry, then fastened it before releasing a lever to let it go. Satisfied that it was working properly, he hauled it up again. Now went to see how the prisoner was getting on.
The condemned man had been given the last rites. The irony of the situation sometimes made the executioner smile. It crossed his mind that if the man – this criminal – had really believed in God, he wouldn't have committed the crime in the first place. Still, who was he to judge? He was only doing his job and the priest was only doing his. It was best not to think about it too much, particularly in this profession.
A guard tied the prisoner's hands together behind his back and led him from the cell. The man shivered slightly as he was taken into the courtyard. Some prisoners struggled, but this one seemed as calm as could be. There was no point resisting the inevitable; it achieved nothing and only made the whole thing more unpleasant for everyone.
The prisoner was pushed forward on to the plank and his head placed in the semicircular groove of the 'lunette'. The executioner fastened the straps around him and instructed him to lie still. Two men standing over by the wall turned their heads away, slightly embarrassed witnesses. They had other thoughts on their minds. The executioner checked once again that the bucket was in place and the prisoner was positioned correctly. He told his colleague to stand clear and moved towards the lever. Everyone was silent.
There was a click. The blade dropped so rapidly that its movement was barely perceptible. The head dropped into the bucket with a soft thud – eleven pounds of brain, bone, muscle and skin gently oozing into the sawdust. It steamed in the cold air. Where the neck had been severed a great arc of blood spurted out. The fountain gradually subsided to a gentle trickle, congealing on the frosty ground.
The two men who had been waiting and trying not to look (although in truth it was almost impossible not to) took this as their cue. The headless corpse was carried inside to a table and its clothes cut off. The men put on their masks and gloves and, working quickly, sliced open the warm body. They weren't too careful with their incisions – the prison would clear up the mess afterwards. However, they needed to be sure not to damage the kidneys they were trying to remove. Within minutes, they had what they wanted. Dousing the organs in fluid designed to keep them alive (similar to the fluids Carrel used in his experiments), they wrapped them in towels and headed for the hospital. These two men – surgeons Charles Dubost and Marcel Servelle – planned to make transplant history.
In the operating room their first patient was being prepared for surgery. The forty-four-year-old woman was lying anaesthetized on the operating table, cloths draped across her, nurses ready with trays of instruments. The bright light and pristine surfaces were in marked contrast to the shabby conditions at the prison. When the surgeons arrived with the dead man's kidneys the organs were doused in more fluid to wash them and prevent them deteriorating. While Dubost and Servelle scrubbed for surgery, one of the kidneys was brought to the operating theatre for transplant.
The surgeons implanted the kidney into a cavity in the woman's pelvis – connecting it into the pelvic blood vessels. The ureter – the tube leaving the kidney, which normally carried urine to the bladder – was passed through a hole in the skin. On the same day, they carried out an identical operation on a twenty-two-year-old woman using the other kidney from the executed prisoner.
At first both operations appeared to have been successful. Within two hours of receiving the transplant, the older woman began to excrete urine from her new kidney. Over the next few days the volume of urine increased. The second patient seemed to be recovering equally well. Perhaps Carrel was wrong; perhaps they could overcome the body's defences? The surgical team was cautiously optimistic, even allowing themselves a low-key celebration.
The forty-four-year-old woman died seventeen days after the operation. The younger woman died suddenly after nineteen days. In both cases the transplanted kidneys had been destroyed by the immune system. The Paris surgeons went on to perform a total of eight transplant operations. They used kidneys from living donors; they washed the kidneys before transplant; they used the best available medication and provided round-the-clock intensive care. Despite all their efforts, every one of the eight patients died (although one lasted more than a month). In each case the new organs seemed to be incompatible. The biological force Carrel had warned about continued to defeat them. But there was every reason to keep trying. The patients the Parisian surgeons operated on were all in the final stages of kidney, or renal, failure. Without functioning kidneys they would certainly die slow, unpleasant deaths.
Kidneys act as filters to the blood. They remove waste products from the body to produce urine. They also help to maintain the right balance of fluids and regulate blood pressure, hormones, minerals and red blood cells (among other functions). The first symptoms of kidney failure include lethargy, nausea and swelling of the ankles as a result of a build-up of fluid. Without treatment, symptoms progress through nausea and breathlessness to confusion, seizures, blindness and eventually coma. It's not called 'end stage' renal failure for nothing.
Unfortunately, there were few effective treatments for acute renal failure in the 1950s. The only alternative to transplants was dialysis, but few hospitals offered it at that time. Dialysis used an artificial membrane to filter waste products from the blood. The process had been invented in the 1920s and developed by a Dutch physician, Willem Kolff, during the Second World War. Kolff's machine consisted of a large tank, cellophane tubing (made from sausage casing) and a rotating drum that resembled a paddle from an old steamboat. This artificial kidney was hooked up to the patient with rubber tubing and the motor switched on.
Kolff's first patient, a twenty-nine-year-old woman, showed dramatic improvements in her condition following dialysis. When she had been admitted to the hospital her eyesight was failing, her heart was enlarged and her breathing was laboured. After dialysis her vision and breathing returned to normal and, reported Kolff, 'her mind was perfectly clear'.
The problem was that every time the doctor needed to use the artificial kidney, he had to cut into major arteries and veins where the blood pressure was strong. He could insert glass tubes into a patient's arms, upper legs, even neck, but each time he did so the blood vessels were irreparably damaged (doctors use the word 'exhausted'). Each site on the body could be used only once, so patients could be attached to the artificial kidney only so many times. Eventually, Kolff ran out of suitable blood vessels. His first patient underwent twelve treatments, but despite his best efforts, she eventually died. Although he had proved that dialysis worked, he had merely prolonged the life of his patients for a few weeks or months, not cured them.
After the war, a few hospitals in Europe and the United States adopted Kolff's technology or built new types of dialysis machine. However, they all ran up against the same problem. Dialysis was difficult, cumbersome and often dangerous. It was a last resort to keep people alive.* Surgeons needed an alternative, and kidney transplants still looked like the best bet. But with only a limited understanding of the immune system, how could they overcome the problems of rejection?
* The problems of dialysis were not solved until the 1960s, when a device made of new types of artificial tubing (a combination of Teflon and plastic) was developed. This 'shunt' was permanently connected to the patient's blood vessels so that they could be easily and repeatedly attached to the dialysis machine.
Surgeons tried everything they could think of. One surgeon had the idea of transplanting a kidney wrapped in a plastic bag. The theory was that the bag would create a barrier against the immune system. The patient survived for six months, but the relative success of the operation was thought to have little to do with the plastic bag. Surgeons suspected that the reason the kidney had lasted so long was that the patient was reasonably well matched to the donor. This seemed to be the key – if the donor and recipient could be matched for blood, tissue type and immunity, the transplant would probably be successful.
In Boston, Massachusetts, the surgeons at Peter Bent Brigham Hospital had been working on the problems of kidney transplants for many years and were becoming increasingly disheartened. Would they ever manage a successful transplant? Finally, in 1954, they hit on some extraordinary good luck.
THE IMPORTANCE OF SHARING
Boston, Massachusetts, October 1954
Richard Herrick was in a terrible state. Since the twenty-three-year-old had been admitted on 26 October he had caused nothing but problems for the staff. He had knocked over equipment and pulled out his catheter. He had cursed doctors and accused them of sexual assault. He had even bitten one poor nurse on the hand while she was trying to change his bedclothes. In the end he was moved to a side room to keep him from disturbing the other patients.
None of this was Richard's fault. He was in the advanced stages of kidney failure, and his psychotic behaviour was its most pronounced symptom. He was only dimly aware of his surroundings, he could no longer recognize people, had little idea where he was and only a tenuous grasp on who he was.
Richard had been referred to the Peter Bent Brigham Hospital as a last resort. If anyone could save his life, it was the surgeons here – the most experienced transplant surgeons in the world. That said, they had yet to perform a single kidney transplant operation with any long-term success. However, Richard hadn't been admitted just because of kidney failure – there was no shortage of equally deserving cases – but because he had an unusual biological quirk. He had a twin brother, Ronald, who was willing to donate one of his own kidneys.
The surgeons knew from previous experiments that transplants could be carried out between identical twins. They had tried transplanting small skin grafts with some success. Identical twins seemed to share the same immune system. Now they had the perfect opportunity to try it out with a kidney. This was a case of the right patient in the right place at the right time. Transplant surgeon Dr Joseph Murray called it 'happenstance favouring a prepared mind'. However, before making the decision to go ahead with the operation the doctors wanted to be doubly sure that the brothers were indeed completely identical twins.
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 future 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.
Kostakis was a visiting research fellow from Greece, but his mother was worried. She was particularly worried about English food, and with good reason. In 1976 English cuisine was, as a rule, lurid, processed and bland. Even the blandest of English foods, the potato, now came in freeze-dried granules; green vegetables were boiled to slime; and Angel Delight – a mousse-like substance with an indeterminate flavour – was considered a sophisticated dessert. Orange juice (in bottles) was a once-a-week treat and bread (white, sliced) had all the nutrients baked out of it as a matter of course. No wonder Mrs Kostakis was worried.
She sent her son a bottle of finest Greek extra virgin olive oil. But before Alkis could drip it on to his salad (iceberg lettuce was probably the best he could hope for), he took the oil into the lab. More in hope than expectation, he decided to try mixing it with the cyclosporine. He had nothing to lose, so he carefully measured out the oil and ladled it over the precious fungus powder. The drug dissolved. He tried out his combination of olive oil and cyclosporine on a series of animal patients. The results were spectacular. They were so spectacular that Calne didn't believe him, so he sent Kostakis back to repeat them. But he got the same results again – cyclosporine mixed with olive oil worked wonders. Soon Calne could start trials in human patients; he would transform the world of transplant surgery. All he had to do was lay his hands on more cyclosporine.
But Sandoz, the company that had discovered cyclosporine, was not convinced. The way things had been going with transplant surgery in recent years, they saw no future in cyclosporine. As far as they were concerned, it would only lose them money. Calne flew out to see them. He talked to their financial people, he argued, he cajoled, he badgered. He told them this was the best thing he had seen in all his years of transplantation. Finally, Sandoz gave in and agreed to conduct a limited drugs trial. They were still reluctant. It would, they warned, almost certainly lose them money.
Surgeons began testing the drug on transplant patients in 1978. With the introduction of cyclosporine, survival rates rocketed. One year after their liver transplant operations some 70 per cent of patients were alive, and almost 80 per cent after kidney transplants. Cyclosporine wasn't without its own side effects, and the risk of infection was still a major problem, but it looked like the immune system had finally been overcome.
In 1990 Joseph Murray was awarded a Nobel prize for his work on organ and cell transplantation (he shared the award with E. Donnall Thomas, who had developed drugs to minimize rejection). Roy Calne was knighted for his transplant research in 1986 and is one of the few surgeons to be elected a fellow of the Royal Society.
In the bloodstained history of surgery, transplants stand out as an area where even the best surgeons have been defeated time and time again. From Spence's disastrous tooth transplants to Carrel's sinister laboratories, experiments with decapitated French criminals and total body irradiation, transplantation surgery is littered with illconceived ideas, gruesome experiments and procedures bordering on the unethical. It took until the mid-1980s for transplant surgery to become a safe, routine surgical treatment. After more than two hundred years the battle with the body's own defences had been won. Now anything was possible. Hearts, livers, lungs, kidneys; surgeons could even transplant a dead man's hand.