How Death Becomes Life

by Joshua Mezrich

  This was the first time anyone had ever been able to transplant tissue between any living creatures and have the graft survive.

  Of course, I didn’t know anything about Medawar as I drove around New York in the middle of the night skinning dead people. But when I did get the chance to scrub in with those organ procurement teams—and watched as the organs were wheeled out in their separate coolers to be flown off into the night, temporarily sleeping before they would be filled again with the warm blood of a new owner and jump back to life as if nothing had happened—I wondered how anyone could possibly have thought this would work. It would never have crossed my mind that it all started with a British zoologist doing skin grafts on mice.

  The effect Peter Medawar’s finding had on the small numbers of surgeons and researchers who were dabbling in the field cannot be overstated. The first three pieces of the puzzle were in place: the technical proof that an organ could be taken from one animal and sewn into another and start working, demonstrated by Carrel; Kolff’s mechanical method of keeping patients in renal failure alive long enough to develop realistic strategies for transplantation in humans; and Medawar’s immunologic proof that there could be strategies to overcome the “biological force” leading to rejection of these organs. With his elegance, honesty, and optimism, Medawar gave hope to those who would follow him that clinical transplantation could become a reality, and inspired a whole generation of investigators to dive headfirst into the game.

  5

  Kidney Beans

  Making Kidney Transplant a Reality

  I have not failed. I’ve just found 10,000 ways that won’t work.

  — THOMAS A. EDISON

  Success is not final, failure is not fatal: it is the courage to continue that counts.

  — WINSTON CHURCHILL

  My path from that operating room on Long Island for my first skin harvest to an operating room in Madison, Wisconsin, transplanting my first kidney as an attending surgeon was anything but straight and easy. It spanned more than thirteen years, four cities, and many all-nighters taking care of patients and needy attending surgeons. In that time, I flirted with the idea of becoming a heart surgeon, a laparoscopic surgeon, and a barista—sometimes I still wish I had—but the excitement of watching a donated kidney make urine in the recipient’s body never left my mind. Throughout my early training, I still wondered whether I could ever actually be the one responsible for making the gift of a transplant happen. Yet as my training progressed, I started to think I was ready. I had scrubbed in on hundreds of kidney transplants during my fellowship, performed all the operations (at least in my mind), taken care of the patients day and night, week after week, and always seemed to know what to do. But of course, there always was an attending present who was ultimately responsible and whom I could silently blame if something went wrong.

  All that changed on my first day as an attending surgeon. Suddenly, almost any decision seemed too difficult. For the first time in my life, no one else would have to double-check my judgment or sign off on my assessment. I could take a patient to the operating room, cut him up, and pull something out, and no one would ask me if I was sure, what my reasoning was, and if I had considered other options. It was terrifying!

  My first kidney transplant was between a wife, a living donor, and her husband, the recipient. He was a redo; it was his second transplant. I met the couple a few days before the surgery. The wife was a nurse, which added to my stress—I was sure she could smell my fear and lack of experience. I examined the recipient. He was a pretty big guy, and I thought the surgery was going to be tough. (It’s always harder to operate on bigger, obese patients. The vessels are deeper and surrounded by fat, making the operation take place in a deep hole. It has always amazed me that people outside of surgery are surprised by this; I suppose they want to believe that all surgeries are the same and predictable.) I started talking to them about the operation, the risks, the recovery, and at some point, the wife interrupted me and asked, “So, how many of these have you done yourself?”

  I wondered if something in my shaking voice had given me away. I wasn’t sure of the best way to handle this and finally said, “Well, this is my first as staff, but I did a couple hundred as a fellow and feel very comfortable with it.”

  I hoped they would ask for a different surgeon. They were both quiet for a minute, and then the husband said, “I think God wants you to do it.”

  I felt like saying, “No, trust me. God does not want me to do it.”

  Thankfully, the recipient’s wife had kept her wits about her. “I think you should get someone else. Nothing personal to you.”

  But the husband said, “No. I really think I want him to do it.”

  “Okay, great,” I stammered. “I’ll take good care of you.”

  “Damn, why is this so freaking tough?” I later said to my fellow as we sewed the vein in. I had opened the recipient on the left side and exposed his iliac artery and vein. The vein was so deep, his abdomen so thick, and the space so small that I could barely see anything. I probably should have made a bigger incision, done something different with my retractors, but at this point I wasn’t going to turn back. I was sweating profusely, my hands were shaking, and I even had them turn down the music in the OR. Where was God?

  Once the vein was done, which took twice as long as I thought it would, we moved on to the artery, and I managed to sew it in. Now came the moment of truth.

  “Reperfusion,” I told anesthesia. “Give my creation life!” I released the clamp on the vein, and then the two clamps on the artery, distal and proximal, and then stared at the pale, flaccid kidney, waiting for it to turn pink and firm.

  Nothing. Nada.

  I felt the artery. No pulse. My heart started to race. Had I “back-walled” the artery—meaning, had I caught the back wall of it while sewing the front? Or had I raised a flap of the intima (the inner layer of the artery, which has three layers), causing a dissection that was now blocking flow into the kidney? Should I take the donor kidney out, flush it, and repeat the whole thing?

  Then I remembered the retractors. Sometimes when they are in deep (as they were with this recipient), they compress the iliac vessels, preventing blood from flowing through them and into the kidney. I pulled the retractors partway up and out of the wound and—voilà! The kidney filled with blood and turned a beautiful pink. Shortly thereafter, urine started to squirt out of the ureter. I was overwhelmed by a feeling of joyful satisfaction.

  Since then, I have done hundreds of kidney transplants, and I promise much more smoothly than that first one. To this day, though, I experience the same feeling of amazement when the organ pinks up and urine squirts out. To this day, I still can’t believe it works—and not just for a few days or a few months. With a little luck, the little beans I successfully transplant into patients should keep pumping out urine for years.

  How did we get to this point, where surgeons can take a kidney out of someone, alive or dead, and successfully put it into someone else? Was it always this easy?

  Boston, Massachusetts, Just Before Midnight, Unspecified Date in 1947

  How must David Hume have felt as he ran to the inpatient ward holding a most unusual package in a sterile pan, hoping no one would see him? The fact that it was midnight, that he was bringing the item to a back room with almost no permanent lighting (rather than the operating room), suggests that he knew very well that what he was about to take part in was not entirely kosher. The patient was a twenty-nine-year-old housewife who had been admitted to the then-named Peter Bent Brigham Hospital after undergoing an illegal, unsterile abortion in her fourth or fifth month of pregnancy. The procedure had led to sepsis, blood hemolysis, and ultimately renal failure. She was treated with antibiotics, and overall, she responded, but she was making no urine. It became obvious to every one involved that she would soon die. If this were to happen today, she would be placed on temporary dialysis until her kidneys recovered. But in 1947 in Boston, dialysis was not yet avail
able. So, what to do?

  Hume and another surgeon, Charles Hufnagel, had been on the lookout for a possible kidney donor. They had both done numerous experiments in dogs by this point, and they knew that a transplanted kidney would last a week at most before it ceased to function. Perhaps a few days of function would give this young woman’s kidneys enough time to kick in. What did they have to lose?

  On this fateful night, there was a stroke of luck. A surgical patient at the hospital died during surgery. A relative of the deceased who happened to be a hospital employee agreed to let Hume take one of the now-useless kidneys to save the life of the young woman. Hume opened the dead donor and removed one of the kidneys carefully and placed it in a basin. How much time had passed from death to procurement is unknown. Without a doubt, enough time had passed that the donor was truly a corpse, not a warm, fresh donor we are used to nowadays.

  Hume and his team would have liked to sew this kidney in place in an OR, where they would have had good lighting, sterile equipment, nursing assistance, and the space to work. But apparently there was “administrative objection to bringing the patient to the operating room. ” Whether this was because of the critical nature of her illness, the illegal abortion she’d undergone, the low likelihood that this surgery would work, or the general resistance to desecrating a dead patient for such a desperate and futile experiment, the decision was made to do the surgery in a side room off the inpatient ward.

  Two gooseneck lamps were pulled into the room. The woman’s arm was placed on a table and prepared sterilely with alcohol. An incision was made in the anterior surface of her elbow. Hume and Hufnagel dissected out the brachial artery and a large vein nearby. Then they sewed the brachial artery to the renal artery, and a vein in the arm to the renal vein. The clamps were released, and the kidney pinked up before their eyes. According to their reports, it also immediately began to produce urine. They tried to tuck it beneath a pocket in the patient’s skin, but there was no space. Instead, they wrapped it in sterile sponges and covered it with rubber sheeting, leaving the tip of the ureter exposed.

  Exactly how much urine the kidney made overnight is unclear. The day after the transplant, Hume and Hufnagel did have to cut back the ureter, as the tip was swelling and obstructing urine flow. This seemed to work. The young woman began to wake up, and two days after the transplant, she was fully alert.

  At that point, Hume and his team noted, the transplanted kidney was petering out, and was removed. Remarkably, the patient’s own kidneys began to recover—she was out of the woods. (Sadly, she died months later from an acute case of hepatitis she acquired from blood transfusions given prior to the kidney transplant.)

  That same year, word was spreading around the world about Kolff’s dialysis machines. George Thorn, the chief of medicine at Peter Brent Brigham Hospital, invited Kolff to visit. Although he didn’t have any spare machines to give Thorn’s team, Kolff did share the blueprints and drawings and presented his experiences with the devices to hospital faculty. Thorn assigned John Merrill, a young but aggressive medical doctor, to work on refining the plans for and building a dialysis machine to be used at “the Brigham,” as the hospital was called. With some modifications, Merrill and his team constructed and tested their own version of Kolff’s machine, and by 1950, they had performed thirty-three dialysis procedures in twenty-six patients. Hume was tasked with obtaining vascular access for these patients—for each run on the machine, he would have to identify an appropriate artery and vein for cannulation (i.e., the insertion of a needle into the vessel), which was no easy job. It wasn’t until 1960 that more permanent techniques for dialysis were developed. Before this, doctors would search the patients’ arms and legs to identify large veins and arteries they could cannulate with the big dialysis needles, sometimes cutting through the skin to get to them. After a few weeks the patients would run out of appropriate vessels, and dialysis would be discontinued. If their kidneys hadn’t recovered, they would simply die.

  Because of Hume’s and Merrill’s successes with hemodialysis, the number of young patients with renal failure seeking treatment increased dramatically. But other than a few sessions of dialysis, there was nothing to offer them. In 1948, Francis (Franny) D. Moore, at the age of thirty-five, became the chairman of surgery at the Brigham. Moore was already a famous surgeon, having conducted practice-changing research on burns and electrolyte management at the larger and more reputable Massachusetts General Hospital. He was a firm believer in applying science to clinical practice and was not afraid to offer risky surgeries or other treatments to improve patient care. Moore was also a key member of the maverick group being assembled to treat patients with end-stage renal disease.

  In 1951 David Hume finished his training and was appointed by Moore, the head of the kidney transplant group at the Brigham, where he began his kidney transplant efforts in humans in earnest. For the medical community, David Hume was a surgeon in the mold of a James Dean, a sort of cultural icon who inspired a generation of transplant surgeons and whose personality remained electrifying despite horrible odds and public dissent about what he was trying to do. Hume couldn’t accept that there were barriers to the things he wanted to accomplish. He was known to spend his daytime hours operating on patients and his nights working on animals in the lab, resembling a “human buzz saw.”

  Shortly after Hume’s appointment as head of kidney transplant, Joseph Murray came on board and took over the efforts in animal experimentation, while Hume remained in charge of human transplantation. By this point, the Brigham had the key pieces in place for success. It had strong department heads in Thorn and Moore. It also had a functioning dialysis machine with an expert in dealing with the medical aspects of kidney failure in John Merrill. But the Brigham wasn’t the only hospital that was getting into the game of kidney transplantation.

  Most notably, two groups in France had embarked on their own transplant programs. One was run by the elegant and cultured urologist René Küss, and another by nephrologist Jean Hamburger. Getting kidneys for donation was no easy task. Brain death had not yet been defined. Nor was the practice of using kidneys from live donors a reality, given that there was virtually no reason to believe the transplant would work. Doctors would have to wait around for a patient to die in the hospital, and then quickly get consent and take the kidneys out, hoping they had a patient nearby to put them into.

  For early transplants in France, these two groups decided to use kidneys from patients who had been sentenced to death and were to be decapitated by the guillotine. The donors gave consent, but this didn’t make the surgeons or anyone else involved any more comfortable. In the words of Küss, “Despite the discomfort of the ‘operation,’ performed on the ground by torchlight, these kidneys were removed with great care and most of them were washed and perfused with Ringer’s solution [i.e., a solution similar to saline] during transport in boxes especially designed for this purpose.” Living donors were typically patients undergoing nephrectomy for some reason.

  The French teams didn’t have much success with these transplants. Most of the transplanted kidneys made urine for some time but ultimately stopped, and the patients succumbed to renal failure and death. Still, some important advances were made. First, Küss and the other French surgeons placed the kidney extraperitoneally (i.e., outside the bag in the abdomen), in the right side, sewing the renal artery and vein to the iliac vessels and plugging the ureter into the bladder, much as we do today. This was much easier than trying to place the kidney in the same spot where the old kidney sat, and much more practical than placing the kidney in the arm or the leg.

  Another advance came from a transplant done by Hamburger’s group. It was December 1952. A sixteen-year-old carpenter named Marius fell off a ladder, landing on his right side. He ended up in a small hospital outside Paris, where his injured right kidney was removed. Shortly after surgery, he was no longer making urine. He was transferred to the care of Hamburger at Necker Hospital in Paris, where it was quick
ly confirmed that he had been born without a left kidney. He was as good as dead. Marius’s mother pleaded with the doctors to take one of her kidneys and place it in her young son. This was a radical request at the time—never before had a kidney been taken from a healthy donor, who would get no medical benefit from the operation, to be used in a transplant that had virtually no chance of lasting long term. Hamburger’s team did ensure that mother and son shared a compatible blood group—that much was known back then. As Hamburger wrote, “Our doubts and hesitation can be imagined, but finally we decided that to turn a deaf ear to the pleas of the family would be no less reprehensible than to agree.” On Christmas Eve, the mother’s left kidney was removed and placed in the right iliac fossa of Marius, similar to how Küss had performed the previous transplants. The kidney worked right away, and the team had high hopes. Marius improved clinically, and his labs normalized. But twenty-two days after transplant, the kidney stopped working. Wrote Hamburger, “This may have been, to start with, only a transplant crisis . . . that can be reversed with suitable treatment, but this knowledge lay in the future.” True, the graft did work longer than expected, perhaps because of the genetic relationship between mother and child. Still, Marius died from renal failure shortly thereafter.