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 ab
out 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 f
or 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.
Blood and Guts Page 16