How Death Becomes Life

by Joshua Mezrich

  In the meantime, pancreas transplantation remains one of the best things we do in transplant. No words can adequately express the relief patients get from the burden of disease when they receive a new pancreas. After a life of painstakingly watching their glucose levels, limiting their diets, carrying around insulin and sugary snacks, worrying about passing out or suddenly having a seizure, and waking up every two hours to check their sugar levels, a new pancreas sets them free in a way no other transplanted organ does.

  9

  Prometheus Revisited

  Liver Transplants and Thomas Starzl

  The myth of Prometheus means that all the sorrows of the world have their seat in the liver. But it needs a brave man to face so horrible a truth.

  — FRANÇOIS MAURIAC, IN LE NOEUD DE VIPÈRES (1932)

  Be calm and strong and patient. Meet failure and disappointment with courage. Rise superior to the trials of life, and never give in to hopelessness or despair. In danger, in adversity, cling to your principles and ideals. Aequanimitas!

  — WILLIAM OSLER

  Madison, Wisconsin, 2:30 a.m.

  “Careful, Bobby. Those veins will bleed like stink.”

  I craned my neck to watch my fellow Bobby carefully dissect the liver off the vena cava. I couldn’t really help him because I was using both my hands to hold up a huge cirrhotic liver so he could work under it. My back was killing me, and my left arm was going numb. We had been in the operating room for about three hours at this point, and still had a long way to go. We’d already dissected out the upper cuff, divided the vessels and the bile duct that go into the liver, and were now peeling the liver off the cava.

  The vena cava is a gigantic vein that carries blood from the whole body back to the heart. The liver hugs the cava tightly, with engorged blood vessels that drain directly from the liver to the cava. Sometimes there can be fifty veins going into the liver, and tearing any of them can lead to torrential bleeding. Of course, this is something we get used to in this business, which is why we have two suction devices going at all times.

  Bobby, who was toward the end of his fellowship, did a masterful job peeling the liver off. At this point, we were almost ready to take it out; the only structures holding it in were the three large hepatic veins that form the upper cuff. This liver had a TIPS catheter in it, shorthand for a transjugular intrahepatic portosystemic shunt, a giant straw that radiologists had snaked into it, through the right hepatic vein, to reduce the resistance to blood flow in this hard, cirrhotic liver. By allowing the blood to flow through the liver, the TIPS dried up all the fluid that had accumulated in the patient’s belly while he was waiting for a donor organ.

  I managed to get clamps around the cava, although I could tell my upper clamp was partially on the TIPS, preventing it from being pulled out. I made a cut into the right hepatic vein, and there was the TIPS, staring at us. I got it better exposed, and Bobby got a clamp around it.

  “You ready, Bobby?”

  We had rehearsed our moves prior to the case, and he tightened his grip on the clamp. I asked anesthesia to lower the patient’s head, to prevent air from entering the pulmonary artery or traveling to the brain if there was an air embolism. Although rare, this deadly complication can occur when you open a large vein, like the hepatic vein, if the pressure of air outside the vein is higher than the pressure of blood returning to the heart, which can be the case in liver surgery. Lowering the head can allow gas bubbles to rise up in the heart rather than travel out the pulmonary artery.

  “Here we go,” I said calmly, and opened my upper clamp. As blood started to well into the field, Bobby pulled hard on the clamp. The TIPS rose out of the heart, and I reclamped the cava. Before I could celebrate, though, I heard someone from anesthesia say over the drape, “Uh-oh, big clot in the heart”—they could see it through their ultrasound probe—“He’s arresting. Better start CPR.”

  Damn. Maybe I was being too much of a cowboy on this one. We pulled the retractors down, and Bobby started CPR. While this was going on, all I could think about was having to talk to the patient’s wife and kids. I could picture their faces the moment I told them he hadn’t made it.

  Despite that vision, I felt weirdly calm and disconnected. After about ten minutes, with all of us covered in sweat, the patient’s heart kicked back in. His blood pressure returned.

  We stood there for a minute, shaking, not sure what to do. Do we get the donor liver out and sew it in? Does his brain still work? Or would that be a waste of an organ we could give to someone else?

  Bobby broke the silence. “Open the new liver. Give me a stitch.”

  “Okay, let’s do it,” I said.

  Don’t worry. Everything turned out fine. The patient’s a veteran. You can’t kill a vet.

  Pittsburgh, 2016

  My alarm was set for 6:00 a.m., but I was up by 5:00. It wasn’t my insomnia this time; I was just excited. It’s not every day you get to meet one of your heroes. I got out of bed, opened my backpack, pulled out my well-worn copy of The Puzzle People, and turned to the first chapter. While I had read the book many times, I wanted to make sure I had the early years down pat. I figured the more I knew about Dr. Thomas Starzl, the more likely he was to open up to me. I had corresponded with him numerous times this past year, but it had taken quite a while for him to agree to me coming to visit. He was more than willing to send me copies of articles he had written about transplant, and summaries already available in the medical literature about the founding fathers of the field, but I wanted something different from him. I wanted to understand how he had been able to do what he did: to persist in a field that no one thought possible, where his initial patients, many of them children, were all dying on the table, and to drag the field kicking and screaming into a clinical reality. He did all this despite much resistance and with fellow clinicians signing petitions for his removal and calling him a murderer. Sure, it is easy to say that those patients would have died anyway, so it’s not that big a deal. But I don’t buy that for a second. Having had a patient die while in my hands; having had to walk out of the OR while everyone was standing in silence looking at me and the patient was lying there cold and lifeless, blood pouring out of the incision and onto the floor; having been the one to have to tell the family about their loved one’s death—I don’t see how it helps to know that the patient would have died anyway.

  Was Tom Starzl made of the same flesh and blood I was? For the longest time, I assumed he was not. Then I found, hidden away in his memoir, tucked inconspicuously on pages 59–60, a surprising and fascinating quote:

  The truth was worse than anyone imagined. For the past six years, I had honed my surgical abilities. At the same time, I harbored anxieties which I was unable to discuss openly until more than three decades later, after I had stopped operating. I had an intense fear of failing the patients who had placed their health or life in my hands . . . Even for simple operations, I would review books to be sure that no mistakes would be made . . . Then sick with apprehension, I would go to the operating room, almost unable to function until the case began.

  He went on to write:

  Later in life, when I told close friends that I did not like to operate, they did not believe me or thought I was joking. Most surgeons whom I know have been able to protect themselves, either by rationalizing errors which they had committed or by promptly erasing the bad memories. I could not do this. Instead of blotting out the failures, I remembered these forever. With growing concern, I came to believe that I was not emotionally equipped to be a surgeon or to deal with its brutality.

  How could someone who felt this way actually have selected the path Starzl walked? Why did he choose to master an operation that no one else could do, one that would surely lead to the death of everyone he operated on? And not just death, but a bloody morass like the aftermath of a crime Jack the Ripper would have admired? I needed to try to understand this better. But would he let me in? Also, Starzl had recently turned ninety. Would he remember th
ose early days of transplantation? Would he have access to all the emotions he felt when starting out?

  Later that day, I stood outside a building across the street from a huge construction site looking at a rather dingy doorway nestled between the Campus Bookstore and the Prince of India on Fifth Avenue in Pittsburgh. I don’t know what I’d been picturing. Maybe a glistening gold door with a carved handle? At the very least, glass doors in the wing of the Transplant Institute. Hell, the entire Transplant Institute at the University of Pittsburgh had been named after this guy, and here he was, tucked away in this dilapidated building. Well, such is life in academic medicine.

  I was buzzed in and began climbing the steep stairs to the second floor. Standing at the top was a smiling elderly man in a blazer and tie. A few steps up, I stepped in a moist puddle of vomit, and Starzl said, “Is that vomit down there? Something must be going on with Chooloo.”

  As I got to the top of the stairs, I saw the perpetrator, a golden retriever looking over to see who was coming in. I remembered that Starzl was a dog lover, even though he had sacrificed so many dogs in his early years of transplant trying to perfect the operation.

  He must have guessed what I was thinking. “The one thing I know, I love dogs,” he said.

  We went into his office, a large room with creaky floorboards and sparse furnishings: a few folding chairs, a large table pushed up against a wall and covered with manuscripts and papers. But it was on the well-stained couch in the corner where this giant of transplant began his story.

  Thomas Starzl was born on March 11, 1926, in Le Mars, Iowa. His father owned and ran the local newspaper and was also a fairly successful and prolific writer of science fiction. Dr. Starzl’s mother had worked as a surgical nurse before he was born, which clearly played some role in his decision to become a surgeon. He grew up under the shadow of the Great Depression, and developed a belief in hard work, an ability to put his head down and work for hours on end, and a sense of responsibility to his family and the people around him. Starzl was not a man who would complain about his lot in life, but he desperately wanted to leave small-town Iowa.

  After a stint in the navy, where an aptitude test suggested he would thrive as a physician, Dr. Starzl entered Northwestern University Medical School, in Chicago, in 1947, and then spent four years at the Johns Hopkins Hospital. He found the experience there brutal. Back then, surgical programs were pyramidal, meaning a majority of residents would ultimately be fired. After four years, Starzl was notified he would not be able to complete his training at Hopkins—which was okay with him. He was ready to get out of Baltimore.

  He spent the next two years at Jackson Memorial Hospital, at the University of Miami, where he performed roughly two thousand surgeries. Somehow, he still managed to set up his own lab, and it was here that he began his first research project examining the liver.

  The liver is a unique organ in that it has the ability to repair itself after injury. Unlike the cells of any other solid organ in the body, hepatocytes, or liver cells, can grow in size or divide. If you cut out half of someone’s liver, the remaining half will regenerate within weeks to months. Regenerate may not be the right word; it doesn’t actually grow back as you might imagine a tail doing on a lizard or a frog. But through a combination of cell growth (hypertrophy) and division, the liver will regain its original size and function. This phenomenon is truly amazing.

  Nonetheless, if enough injury occurs over enough time, the liver can shrink and be totally replaced with scar tissue, losing its regenerative ability as its architecture gets more and more disrupted. Once it reaches this end-stage state, it is termed cirrhotic. The problem with cirrhosis is twofold: First, the liver can become dysfunctional, no longer able to make the various proteins and clotting factors it is charged with making, and no longer able to detoxify the various wastes or break down the products that pass through it on their way from the intestines. This can cause confusion in patients and spontaneous bleeding. The liver can also lose its ability to make and drain bile, so patients turn yellow (become jaundiced). Second, a knotty, shrunken liver (which is what most cirrhotic livers become) can impede blood flow. Despite its normally high flow, in cases of cirrhosis, the portal vein backs up and can’t push blood through this highly resistant organ. This backup of blood leads to the distension of this already huge vein and the reversal of flow away from the liver. When this happens, many small veins coming off the portal system get distended, becoming varices (literally, dilated veins). This includes the veins that run along and into the esophagus; these veins can spontaneously rupture, an extremely life-threatening condition and one that can be very dramatic: patients can show up at the hospital vomiting massive quantities of blood and die right in front of you. A second complication of the backup of blood flow in the portal vein is ascites, or (nonblood) fluid that accumulates in the patient’s belly, sometimes ten liters or more. This leads to the characteristic appearance of a patient in liver failure: yellow, swollen, and often looking nine months pregnant.

  There weren’t many options for patients presenting with cirrhosis and esophageal bleeding in 1955. A number of operations had been designed to divert blood around the liver as it took its path from the organs of the gut back to the heart. Starzl was involved in one of these operations, in Miami, and he was surprised to note that when the patient’s liver was bypassed, his diabetes was cured. Starzl was fascinated by this case and decided he would study it in animals. Disappointed to find that there was no large animal facility at Miami, he set one up in an empty garage located near the hospital, “borrowing” equipment from the hospital to make it work and enlisting his wife and a junior resident to care for the animals. They got dogs from the city pound, made them diabetic using chemicals toxic to the cells in the pancreas that make insulin (beta cells), and then performed these same operations, bypassing blood around the liver. Lo and behold, the diabetes . . . got worse.

  Starzl felt that his hypothesis could not really be tested without removing the liver entirely, so he developed a technique for total hepatectomy. Of course, the dogs could survive only a day at most, but this was Starzl’s first step on the path to liver transplantation. “The most important consequence of the liver removal operation was the realization that a new liver could be installed (I thought quite easily) in the empty space from which the normal liver had been taken out,” he would later write in The Puzzle People. “In fact, half the operation of liver transplantation already had been perfected with the hepatectomy procedure. The other half would be to sew in a new liver.” At this point, he was hooked.

  AFTER HIS TIME in Miami, Starzl returned to Northwestern in 1958. He decided to take an extra year of training as a fellow in chest surgery. He knew his passion was the liver, but despite being gifted at surgery, he was tortured by the idea of performing it, and much preferred research. During his fellowship at Northwestern, he conducted liver transplants in dogs in his lab (with no assistants). All the dogs died. This would be harder than he’d expected. As he completed his last year of training, he agreed to stay on at Northwestern to continue his research. After obtaining a couple of national grants, he was off. Not only did he develop the techniques in dogs that would be necessary for attempting liver transplantation in humans, but he also was finally exposed to the handful of other investigators working in the field of liver transplantation.

  At the Brigham more or less at the same time, Francis Moore also had turned his attention to the liver. He put a group together and performed numerous liver transplants in dogs. Early attempts failed for him, too, as the dogs did not tolerate the clamping of the vena cava and portal vein that was required at the time to get the liver out.

  Both Starzl and Moore came up with the same solution to this problem. They obtained plastic tubing and shunted blood from the lower extremities into a vein in the neck that drains into the heart. In this way, when they clamped the cava, blood would bypass the clamped vein and make it back to the heart. (Their technique is still used tod
ay in some programs.) Once this problem was solved, both groups were able to transplant the liver in dogs successfully and saw slowly improving survival rates. Of course, neither group was using immunosuppression, as there was none at the time. But even though all the livers were rejected in about a week, during that week, the labs normalized, suggesting the livers were functioning, and the dogs behaved normally.

  At the annual meeting of the American Surgical Association, Franny Moore presented the Brigham data. His description of liver transplantation was seen as groundbreaking—until Tom Starzl got up to discuss Moore’s paper. As Starzl recalls:

  My approach had been and would continue to be strongly influenced by my original interest in the effect of portal blood (and insulin) on the liver. In more than eighty transplant experiments, I had systematically tested different ways of restoring the transplanted liver’s blood supply. We showed that livers which were given a normal portal venous inflow performed better than those which were not. But the important achievement for the moment was that we had eighteen dogs with survival greater than four days, with one animal living for twenty and one-half days. I realized that we were ahead of the Boston team.