How Death Becomes Life

by Joshua Mezrich

  It is truly a miserable process. In addition to being confined to a chair for four hours three times a week, many patients feel lousy during and after the sessions, with symptoms that include fatigue, coldness, headache, and muscle cramps. After dialysis, patients will often spend the rest of that day lying in bed. As many patients have described it to me, dialysis keeps you alive but is no way to live. But then again, what’s the alternative?

  When dialysis was first introduced, the man responsible would never in a million years have considered it an option for long-term treatment. At the time, Willem Kolff was building his dialysis machine in secret in Nazi-occupied Holland, using sausage casings and the motor of a sewing machine, all the while helping the Dutch resistance against the Germans.

  Kolff was born in Leiden, in the Netherlands, in 1911. His father, who started as a family physician, ultimately settled on running a tuberculosis sanatorium. Kolff had significant exposure to his father’s practice, and he became fascinated with medicine. He also had a knack for woodworking and mechanical fixes. What he enjoyed most about the prospect of a career in medicine was the opportunity to solve problems, particularly by building something with his hands.

  Kolff finished medical school in 1938 and began his practice. There are numerous examples of him inventing things to help his patients, including an early version of a sequential-compression device—“squeezy boots,” as we call them, which strap around patients’ legs and periodically inflate and deflate to prevent blood clots. Kolff’s first real exposure to renal failure and the helplessness associated with caring for patients with this disease was with a patient named Jan Bruning, twenty-seven, who died before his eyes. Bruning had Bright’s disease, a historical term for many different causes of kidney disease, some of which can recover and some of which cannot. Back in the 1930s, there were all kinds of useless treatments for Bright’s, including dietary changes, bloodletting (rarely a good option), and baths (which sounds nice, at least). Yet this didn’t sit right with Kolff. He hadn’t become a doctor to watch some young man die in front of him while giving him a bath. He figured it this way: kidneys are just filters that clean waste products from the blood, and he knew one of the key toxins was urea. How hard could it be, then, to filter the blood? If he could just clean out the blood for a short period, perhaps he could give the kidneys some time to rest and recover.

  This idea had been tried a couple of times prior to World War I, but with little success. At that time, the type of membrane that would allow molecules of certain sizes to flow across a gradient, but that would be impermeable to bigger molecules, including blood cells and important proteins, didn’t yet exist. In addition, any blood placed in a container for exposure to such a membrane would clot. Kolff knew he could get over both these barriers because . . . he liked sausages—or, at least, he was aware that sausages were encased in cellophane, an edible artificial membrane made from regenerated cellulose that allows sausages to keep their shape and allows flavors to diffuse across the membrane. He also was aware that cellophane was already being used as a filter for purifying fruit juice. It seemed to Kolff and a few of his colleagues that if he could expose blood to a cellophane barrier with a lot of surface area, and have, on the other side of the membrane, a fluid bath without urea (and without any other protein or electrolyte he wanted to remove), he could cleanse (or dialyze) the blood. He drew off enough of his own blood to fill a sausage casing and mixed this with urea at a concentration he estimated would be found in the blood of a patient in renal failure. He then poured this into the casing and placed it on a board floating in a bath of water. He added a small motor to the board, so it would rock back and forth, sloshing the blood around and thus allowing it to come in contact with the cellophane membrane. Five minutes later, he retrieved the blood sample and, to his surprise, found that almost all the urea had been transferred over to the bath! Thus, dialysis was invented.

  There were still challenges, though: having enough surface area for blood to contact the cellophane, avoiding clots while the blood was being filtered, figuring out how to get the blood from the patient into the filter system and back, not to mention knowing how much blood to pull out and then put back in without killing the patient. Yet, as with so many pioneers, the right combination of intelligence, vision, conviction, an ability to ignore the naysayers, and near obsession regardless of these barriers made Kolff the man for the job. Still, in addition to the technical challenges, Kolff had to deal with one other major impediment: the Nazis.

  The Netherlands was invaded on May 10, 1940, and the Dutch army defeated in less than a week. This was devastating for Kolff, who despised Nazi policies. He had many Jewish friends and colleagues and had witnessed their deportation, murder, and, sadly, many suicides among them. Perhaps most impactful for him had been the death of his boss and mentor, Leonard Polak Daniels, one of the few established physicians who believed in Kolff’s visionary medical inventions. After the Germans invaded and conquered the Netherlands, Daniels killed himself rather than be taken by Hitler’s army. His replacement at the large university hospital in Groningen was a staunch supporter of Hitler, a fact that prompted Kolff to secure an appointment in a small hospital in the town of Kampen, effective in July 1941. This move proved to be fortuitous, as it gave Kolff the chance to move forward with his plans without much scrutiny.

  Kolff had two main goals when he went to Kampen. The first was to treat as many patients as possible, including those with renal failure. The second was to save as many people as possible from the Germans. To prevent the deportation of suspected members of the resistance, he made up fake illnesses for them, shielded others who were being investigated by hiring them, became involved in an aborted assassination plot to kill the Nazi head of police—he was to have driven the getaway car—and even agreed (though was not in the end required) to cut up and dispose of the body of a Jewish woman who had died while friends were hiding her from the Nazis. He also administered medicine to people that made their skin turn yellow, so the Nazis would think they had jaundice and couldn’t work in their camps.

  Amid all this, Kolff also found time to build the first dialysis machine. After the success of his original experiment using his own blood, he let his mind wander regarding how to increase the exposure of blood to the cellophane and how to get blood to flow out of the patient, through the cellophane casing, and back into the patient. In 1942, he thought he had the answer. Early one morning, he walked over to an enamel works owned by Hendrik Berk, and together, Kolff, Berk, and Berk’s engineer E. C. van Dijk came up with a plan for a machine.

  It really was quite simple. Blood was drawn from a patient and flowed into a central shaft within a large cylinder. The shaft had multiple spokes that connected out to cellophane tubing. This tubing, which was long and thin, wrapped in spirals around the big cylinder. The cylinder was suspended horizontally in the dialysate (the fluid that would serve to pull the toxins out of the blood) and attached to a motor that allowed it to spin. With each turn, the blood, obeying the laws of gravity, flowed into the cellophane, which became immersed in the dialysate as the cylinder spun. The toxins and electrolytes flowed across the permeable membrane and into the dialysate bath (which was made up of a low concentration of sodium chloride, sodium bicarbonate, and potassium chloride mixed in a large quantity of tap water. Kolff was constantly monitoring electrolytes and urea in the patients’ blood, and would make adjustments to the bath depending on these levels and how fast he wanted to correct imbalances. Eventually he added glucose to the bath as well, to help pull water from the patients’ blood and prevent disequilibrium of electrolytes. Although Kolff always described dialysis as simple, it is actually quite complex, and his constant attention and analysis during sessions was as important as any of his innovations in the ultimate success of his machines). It was a closed circuit that allowed the blood to progress from the patient through the rotating loops of cellophane while being exposed to the dialysate, and then back into the patient.

/>   The first dialysis machine had been built. Now all Kolff had to do was see if it worked. For this, he went straight to human patients, choosing those who clearly were going to die without any intervention. His first attempt was less than stellar. He tried the machine on an elderly Jewish patient who was so ill the Germans didn’t bother to deport him to a concentration camp with the rest of his family. Kolff initially had trouble getting blood out of the man’s brittle arteries, and in the end was able to inject a mere fifty milliliters of blood through the machine. Then the cellophane sprang a leak, causing the bath to become foamy red and spill all over the floor. His second patient was a much better candidate—a twenty-eight-year-old woman who had been previously healthy but who, for unknown reasons, had developed kidney failure, presenting with high blood pressure, confusion, loss of vision, and palpitations. She was found to be in renal failure with an extremely high level of urea in her blood. Kolff thought there was a chance that if he cleansed her blood for a few days, her kidneys could recover. For the first session, he removed half a liter of blood from an artery in the patient’s wrist, ran it through his machine, and returned it to her through a needle in a vein in her arm. She regained consciousness and seemed better. Kolff watched her for a day, and when nothing bad happened, he decided to resume dialysis. By this time, he had designed a pulley system whereby he could lower portions of the contraption to allow blood to come into the machine and raise different parts when he wanted the blood to return to the patient. The patient underwent twelve sessions of dialysis in all, the tenth session lasting six hours. Throughout the process, Kolff carefully followed the woman’s lab results, including electrolyte and urea levels, and everything was correcting nicely. By the end, he ran twenty liters of blood through his machine during a single session, as much as four times the patient’s blood volume. Her blood pressure normalized, and her mental status had improved. By the end, Kolff was hooking her directly to the machine and letting her blood flow through the dialyzer and back into her body—truly the first case of continuous dialysis ever performed. This was 1943. By the twenty-sixth day, Kolff finally had to stop. The dialyzer was still working, but the woman’s kidneys had not recovered, and he couldn’t find any more blood vessels. The needles Kolff had access to were very primitive, and each vessel could only be punctured once. With every new session he had to find a new artery and vein to access. She died shortly thereafter from renal failure.

  Kolff immediately got to work on building a second, even bigger machine, this time constructed out of wood; with the war raging, aluminum was no longer available in the Netherlands. He moved his first machine over to a hospital in The Hague and set up his new one in Kampen. Then he got the word out that he was looking for patients. He even tried to hold weekly conferences to discuss his capabilities. Somehow, despite the worsening conditions in the war, he managed to build a third machine, which he placed in Amsterdam.

  Over a two-year period, Willem Kolff dialyzed sixteen patients secretly at night. Only one patient survived, but Kolff was the first to admit that it wasn’t from his dialysis. Even so, he knew he had made great progress. He had made many improvements to his machines, and was now able to achieve a flow rate of 150 milliliters of blood per minute through his tubing, which was, all told, about 45 meters long. He was convinced that if he could just get the right patient, someone who wasn’t so far along in his kidney disease that it was too late and whose native kidney function could recover, his machine would work.

  He finally got his chance in 1945, when peace returned to the Netherlands. Ironically, that first successful patient would be an imprisoned Nazi sympathizer. Her name was Sofia Schafstadt, a sixty-seven-year-old with an inflamed gall bladder. Her illness and the antibiotics she was taking to treat her infected gall bladder had caused her kidneys to fail. Over an eight-day period she had made almost no urine, her urea levels were dangerously high, and she was slipping in and out of a coma. Kolff finally convinced her team to let him dialyze her, and because they figured she was going to die anyway (and because she was a Nazi sympathizer and they didn’t really care), they let him.

  The first session lasted more than eleven hours, and by the end the patient was awake, the urea level in her blood had normalized, and her blood pressure had come down to a safe level. Kolff watched her closely over the next day, and when he was getting ready to hook her up to the machine again, she started to make urine on her own. Kolff was sure that without the dialysis session, she would have died.

  How remarkable that Kolff was able to accomplish all that he did in the environment in which he worked. But he didn’t stop there. After the war, he and his assistants traveled the world, telling anyone who would listen about his invention. He gave away his beloved dialysis machines and, once he ran out of the machines, provided blueprints for constructing them. It probably never occurred to him that dialysis would be used as a chronic treatment for kidney disease. I imagine he would have been as shocked as I was the first time I walked into a dialysis unit as a medical student and saw countless people sitting in lounge chairs, large tubing filled with blood running from needles in their extended arms into mysterious whirring machines that would periodically emit shrill alarms that everyone but I seemed to ignore. The machines look so complicated and industrial now that I had never realized how simple the concept and early design for them was until I started researching this book.

  Kolff saw dialysis as a temporary measure, something that would give the patients’ native kidneys time to recover. When it became clear that the majority of his patients would not see such a recovery, he turned his attention to the next step on the road to curing them: kidney transplantation. He ultimately made his way to the Cleveland Clinic, where he became involved in its kidney transplant program, and he remained active in the transplant community throughout his career. He was also one of the innovators in the development of the membrane oxygenator for cardiac bypass, and ended up at the University of Utah, where he was one of the inventors of the most famous version of the artificial heart. Kolff’s contributions to the field of organ replacement are truly legendary, and his persistence in establishing dialysis allowed others to take the next step in achieving success in organ transplantation. It was the advent of dialysis that allowed a few premier hospitals to become destination centers for patients in renal failure, and that bought their physicians time to think about more permanent ways to treat their disease. Yet before this could be a possibility, before someone could build on the advances of Alexis Carrel and Willem Kolff, someone had to crack the barrier of the immune system.

  4

  Skin Harvest

  I cannot give any scientist of any age better advice than this: the intensity of the conviction that a hypothesis is true has no bearing on whether it is true or not.

  — PETER MEDAWAR, ADVICE TO A YOUNG SCIENTIST

  The first time I ever took from death was on a crisp October evening during my second year of medical school and a full year before I witnessed my first kidney transplant. Of all the ghoulish things I have been involved with during my career as a transplant surgeon, what happened that evening has to be the most bizarre.

  I had just started working for the New York Firefighters Skin Bank, an organization set up by the burn center at New York Hospital in 1978 to recover and store skin from recently deceased donors. A couple of medical students from each class were handpicked to work for the skin bank, to join an “elite” group that would head out in the middle of the night to skin dead people. Of course, there was a purpose to it: the skin would be used as temporary grafts for burn victims, to give them coverage while they healed enough to undergo grafts with skin from their own bodies.

  Picture the case of a factory worker who falls backward into a vat of boiling oil, or a young man who gets caught in a house fire when his meth lab explodes—these are two actual patients I took care of years later, in my residency. Both these men came in with more than 80 percent of their bodies covered in full-thickness burns. With the los
s of that much skin, our barrier to the outside world, both men were losing fluids and electrolytes through their open wounds, couldn’t maintain their body temperatures, and were at high risk of infection from the bacteria we encounter every day. In addition to resuscitating them with aggressive IV fluid infusion, it is critical to get some sort of coverage over their wounds, ideally by taking skin from preserved (that is, unburned) sites on their own bodies, so that the grafts take and are not rejected. But given the extensive nature of these two patients’ burns, it would take months and countless trips to the operating room to harvest enough skin to cover the open areas. So, in their case, we had to use someone else’s skin.

  We know that using a graft from someone else will surely end in rejection, but we also know that patients who have suffered serious burns generally have a poor immune response—which, ironically, allows a skin graft from a donor to last for weeks, much longer than it would in a healthy recipient. And this temporary coverage can buy enough time for these very ill patients to be stabilized.

  Nowadays, skin substitutes compete with cadaveric skin, but back in the 1990s, when I was working at the skin bank, no other substitute had been approved, so donors had to be used.

  At the time I was chosen to harvest donor skin, I didn’t have any concept of who had figured out how to do it, how skin grafts related to the field of organ transplantation, or how relevant this work would eventually become to my life. As a second-year medical student, I hadn’t yet started my clinical rotations where we see patients, had never actually taken care of a patient with an illness, and still had it in my head that I would become a pediatric oncologist. I just thought it would be fun to be part of this team and was intrigued by the idea of learning new skills and spending some time in an operating room.