How Death Becomes Life

by Joshua Mezrich

  If Alexis Carrel had followed his instincts, he very likely could have become the true father of transplantation and perhaps one of the greatest innovators in the history of medicine. If he had simply died or faded away shortly after the Nobel Prize he won in 1912, at the very least he may have been revered as one of the premier experimental surgeons of the twentieth century. Instead, as his research production dwindled and his relationship with Charles Lindbergh blossomed, Carrel focused more and more on the degeneration of mankind and how he could play a role in studying this in a scientific way. He always had a fascination with strongmen such as Mussolini and Hitler, and thought that in the 1930s, German society was taking a good approach to cleaning up its population.

  Shortly after the liberation of France from the Nazis in August 1944, various rumors emerged that Carrel was under house arrest, was going to be tried as a German collaborator, or was on the run. None of this was true. He had fallen ill from heart disease, having suffered his first heart attack in 1943, and died in November 1944. Although he was not formally charged with any crimes, his name became strongly associated with Nazism, fascism, and anti-Semitism. His reputation was destroyed, and to some degree, many of his discoveries were lost. His transplant work was completely forgotten, with little mention made of it to this day.

  Sir Roy Calne, the man who perhaps more than anyone moved the field in the direction of chemical immunosuppression, had this to say about Carrel: “Alexis Carrel was a brilliant researcher, but not a very nice man.” Despite that, his contributions with regard to the technical aspects of sewing vessels together and transplanting organs from one animal to another with initial graft function represent the first piece of the puzzle of organ transplantation.

  Part II

  The Making

  of a

  Transplant

  Surgeon

  Only one who devotes himself to a cause with his whole strength and soul can be a true master. For this reason mastery demands all of a person.

  — ALBERT EINSTEIN

  3

  The Simple Beauty of the Kidney

  In order to attain the impossible, one must attempt the absurd.

  — MIGUEL DE CERVANTES

  What does a kidney transplant look like, from the beginning? Assume the patient is asleep on his back on the operating table, prepped and draped. I first identify my landmarks on the abdomen, making a mark on the patient’s belly with an erasable marker. I mark the rib cage, anterior-superior iliac spine (hip bone), and pelvis. I then put a mark two finger widths medial to the hip bone and draw a line that goes from the pelvis through this mark and up to the rib cage. The line will look like a curved incision that goes from the pelvis, up the abdomen, and ends just above the belly button. I usually do it on the right side, because the blood vessels are a bit more toward the front on this side. We can use the left as well, which is what we do for retransplants (when a first transplant fails). I now take the knife and cut through the skin along the line. I then use the Bovie electrocautery, which uses electric current to heat, divide, and cauterize tissue, to cut through the fat and down to the muscle layer. I then continue through the external oblique muscle, internal oblique muscle, and transversalis muscle and fascia. I actually divide these muscles, and even though the patient is asleep, the muscles contract in response to the electric current, jumping back and forth.

  I now identify the peritoneum, that is, the “bag” that surrounds the intra-abdominal organs. The small and large bowel, stomach, spleen, liver, and part of the pancreas all sit inside this bag, and you have to cut through it to get to them. Other organs (kidneys, part of the pancreas, part of the duodenum, and big blood vessels including the aorta and IVC, or inferior vena cava) sit behind this bag, so you have to push it out of the way to get to them. In a kidney transplant, we don’t typically remove the sick kidneys but, rather, place the new kidney lower down on the blood vessels that ultimately go down the leg. In the early days of transplant, the native kidneys often were removed, but eventually it became clear that this added more surgery with no benefit.

  Trying not to make a hole in the peritoneum, I pull it out of the way, and behind it I start to see the iliac artery and vein, and the patient’s ureter. I dissect out the iliac artery and vein (which continue down the leg). This involves using scissors, forceps, and the Bovie to divide fat, lymph, and small blood vessels off these structures. I tie off any small vessels that I think might bleed (which means I take a silk suture and tie these little guys just like you might tie your shoelace). This part of the operation can be really easy, but in someone who has had previous surgery, or who has a lot of atherosclerosis (plaque in their arteries) or is obese, it can be much harder.

  At this point, I focus on the donor kidney. In most cases, I’ve gotten it ready while anesthesia is putting the patient to sleep. (Back-table surgery, as this is called, is very specific to the field of transplant. It takes a while to learn, because the organs can be held upside down and the blood vessels are empty and flaccid, making it easy for a surgeon to inadvertently cut them in half. In addition, every kidney is different. Some have multiple arteries, some have multiple veins, and some even have two ureters!) I meticulously clean the excess fat off the donor kidney and then have an assistant hold the renal artery toward me while I dissect up it, tying off all the little side branches. I do the same to the vein. In doing this, I take care not to injure the ureter and its blood supply. If there are multiple arteries to the kidney, I need to decide if I can sew them into the patient with one big Carrel patch that includes all the orifices. If two arteries are too far apart, I have to decide if I will “pants” them together—that is, make a slit down the lumen (the opening of the artery) and then sew them together, making one lumen out of two—or, alternatively, if I will just implant the arteries separately onto the iliac artery. I then flush the vessels with cold saline, stitching up any small holes I find when the saline squirts out of them.

  It’s better to do all this on the back table than in the patient. Surgery is all about predicting where something bad might happen and then doing something to prevent that from happening. I take my time on the back table, the most critical point of the case.

  Now I am ready for implantation. I have the anesthesiologist give the mannitol and Lasix to protect the patient from the evil humors that are released when blood flow is restored to the kidney. I place a side-biting clamp on the iliac vein of the recipient, then cut a slit in the vein, making sure not to get too close to the clamp. Using angled scissors, I extend this slit to match the size of the renal vein from the donor kidney. I then bring the kidney up on the table. I get a 6–0 Prolene suture—Prolene is nonabsorbable, meaning it will be there forever—and put one stitch inside out through one end of the iliac vein and the other end inside out in the donor renal vein. I put a second one similarly in the other end, inside out in the iliac vein and donor renal vein. I like to put a third stay suture in the middle for retraction, again inside out and inside out. Then I drop the kidney down into the field and carefully tie the sutures, three to four knots in each. I have an assistant retract the kidney away from me, and I load one of the needles. I then run the suture from one end to the other, outside in, inside out, being sure not to catch the back wall. Once one side is done, I tie the suture to the one I had placed at the end—seven knots. I flip the kidney back to me and take out the stay suture. I then sew the other side, from one end to the other.

  Now I turn my attention to the artery. I place clamps above and below where I plan to sew, taking particular care not to injure the artery by clamping too hard. I then make a small hole in the artery and use a circular punch to punch out a bigger hole—somewhere between four and six millimeters in diameter. (Although it can be smaller, I try to match it to the size of the donor vessel.) I get another 6–0 Prolene suture and, again, go inside out on the iliac artery and then the renal artery. I pull the artery down toward the iliac and tie it down—four knots. Then I pass the Prolene behind the art
ery and sew the back wall first, from the outside. Outside in, inside out—every stitch needs to be perfect. The first few stitches on this anastomosis can be a bit challenging and awkward, but once you have done it a few hundred times, it gets easy. No back walls, no dissections—it is critical to get all the layers of the artery when you sew this, so you don’t raise a flap. (Arteries have three layers, whereas veins have one. If the inner, intimal layer separates from the outer two layers, it can become a flap, and over time blood can dissect into this layer and cause the artery to clot.) Then, the moment of truth.

  I release the clamps and watch the newly transplanted donor kidney turn pink. A minute later, it squirts urine into our field and on our hands while we continue working. What a beautiful sight! I spend a few minutes drying things up, and then move on. I pull the bladder, which is really just a muscular bag—yet hard to find in a big, deep person—up into the field. I have gotten in the habit of having the nurses fill the bladder from below (through a catheter that goes through the urethra and into the bladder) with blue fluid. This way, I can stick a needle in any structure that looks like the bladder and be sure the syringe is sucking up blue fluid. When I successfully find the bladder and see my beautiful blue dye, I open it up and sew the ureter onto it over a stent. I then dry things up again. Then I close the muscle and fascia in two layers, making sure not to nail the peritoneum or its contents.

  Again, everything needs to be perfect. It doesn’t matter how tired or distracted you are, how many things might be going on with other patients or with your boss or your lab or in your personal life. It needs to be perfect. Otherwise, the patient will pay a huge price, the donor won’t have given the gift of life, and you will be woken in the middle of the night by a shrill pager letting you know you’ve screwed up, it is your fault, and now you have to deal with it.

  That’s a kidney transplant. No big deal, but one of the best things we do in health care.

  The kidney is an exquisite organ. I like to tell my residents that “the dumbest kidney is smarter than the smartest doctor.” In a healthy person with a working organ, blood flows into the kidney and goes through an ingenious system of glomeruli—that is, circular tufts of thin blood vessels surrounding the tubules of the kidney. Across the kidney’s membranes and structures, toxins, wastes, and electrolytes are filtered out into the tubules to be secreted as urine. Kidneys are also involved in controlling blood pressure and stimulating the production of red blood cells. It’s amazing how a working kidney seems to know exactly what to do with fluids and reabsorption, whereas we doctors have so much trouble regulating fluid in patients, no matter how many labs and vitals we check.

  In part due to that complexity, and the significance of this organ in a functioning body, up until the 1960s, patients with kidney failure would simply die. Chronic or intermittent dialysis, which is essentially renal replacement therapy (in which people are hooked up to a machine that filters blood), didn’t become a reality until then. The futility of treating patients with kidney disease is what inspired Alexis Carrel to take the first step toward making transplant a reality, simply sewing a kidney from one animal into another. But many more steps would need to follow, all inspired by the desperation of watching young men and women die because they had lost the ability to urinate.

  And so, it was fitting that it was a kidney transplant that started me on the path to becoming a transplant surgeon.

  Cornell University Medical College, New York City, Third Year of Medical School

  When I started my third year of medical school, I still had the idea that I would be a pediatric oncologist—until I did a rotation on a pediatric service. It didn’t take me very long to realize that that was not the field for me. The pace was slow, the parents were challenging, and I spent too much time doing well-baby checkups. I then did obstetrics and gynecology, and while I did enjoy this more, especially the excitement of delivering my first baby, it didn’t take me long to realize I was not a budding gynecologist. My internal medicine rotation came next. I got to talk to patients, listen to their stories, and figure out what might be wrong with them, but I didn’t like the pace or the chronicity of the diseases we would deal with. Everyone had diabetes, hypertension, or cancer, and we weren’t going to cure any of these conditions. We would see twenty-five patients in the clinic a day, each one for only fifteen minutes, which wasn’t enough time to address any of the multitude of problems each had. We would focus on one or two issues, adjust a few meds, prescribe some new ones, and move on, unsure that any of the lifestyle and medication changes we’d suggested would actually happen.

  Next came surgery. My rotation started early in January, shortly after the holidays. I had come in at about 4:30 in the morning to do rounds—visit some patients, gather their labs, and write their progress notes (daily notes written in the chart of every patient). Other than the sound of the nurses and the few medical students on the surgical services gathering patient information, it was quiet in the hospital. The interns showed up at around 5:30, and the medical students updated them on the patients. At 7:00 a.m. we met in the cafeteria to present the cases to the chief resident. The medical students sat silently at the table, not daring to talk or eat. The third-year resident presented the patients to the chief resident, and, turning her sharp gaze on the interns, commanded them to clarify any details she didn’t know. The chief listened, casually eating a donut.

  I went to the operating room at 7:30 and scrubbed in on two elective cases, a resection (removal) of a rectal tumor and a liver resection, during which I was soundly criticized for my inability to cut sutures well. Then I did rounds again with the team, gathered more patient data, and went to a conference. At some point during the day, I was told I would be on call that night. This was good training for the next twelve years of my life. Don’t make plans. You are expected to be available days, nights, weekends, holidays, and family birthdays.

  At about ten o’clock in the evening, we took a patient to the operating room for a bowel obstruction. I had been both too nervous and too busy to eat that entire day. I started to feel dizzy. I remember looking at the patient’s distended bowel, with its liquid contents sloshing around. I started to feel faint and was sweating profusely. Somehow, I gritted my teeth and got through it. As the case was ending, my resident told me to go scrub in next door—it was about 2:00 a.m. now—where they were starting a kidney transplant.

  All I really wanted to do was go to bed, but I went. And it was amazing. Dr. Stubenbord was the transplant surgeon. I’ll never forget the simple beauty of the kidney transplant, the feeling of wonder when the kidney turned pink. There was this remarkable sense in that room, in the middle of the night, with classical music playing and urine pouring onto our hands, that we were doing something miraculous. Someone who had just died had saved the life of someone he had never met, and we were the ones who’d helped make that happen. (Well, not me, really; I just watched.) How crazy was that? I wondered what other organs you could do this with. I really had no idea at the time, but I knew I wanted to find out. I was hooked.

  Those three months on the surgery rotation ended up having a huge impact on my life. In many ways, I stumbled into surgery. Still, it felt like a calling—albeit, one that involved a massive commitment and an overwhelming responsibility: to take someone’s life in your hands and take responsibility for what happened next. The satisfaction of doing an operation well, of pushing yourself to get everything right and make someone better—it is intoxicating, almost godlike. I also loved the team I worked with during those three months; we functioned like a well-oiled machine.

  Toward the end of our third year, our advisors asked us what field we wanted to go into. I couldn’t stop thinking about that kidney transplant. I had scrubbed in on a few more during my time on the surgery rotation, and I remained fascinated. I never saw a liver or a pancreas or a heart transplant. Still, I could not get over that we could take a kidney from someone who had just died and plug it into someone else, maybe even a
day later, and it would start working. It seemed so simple. I wondered then if I would ever be able to do something like that myself.

  WHILE ALEXIS CARREL showed it might be technically possible to transplant a kidney from one living being to another, this alone did little to alleviate the desperation both of patients with renal failure, and of their doctors, in the first half of the twentieth century. It would take another advance in the care of these patients before transplant could be considered a clinical option. Enter the remarkable story of dialysis.

  Something about dialysis units always reminds me of the film The Matrix—not the part where Neo is able to dodge bullets while moving in slow motion, but the part where people are plugged into the matrix through sockets at the back of their necks. That is more or less how dialysis works, and it seems totally barbaric.

  When someone’s kidneys stop working, the blood has to be filtered in some way, or the patient will die. The most common method of dialysis is hemodialysis, or dialysis through the blood. In order to perform hemodialysis, we first establish an access where the needle can be inserted. Typically, a surgeon will make an incision on either your forearm or your upper arm and sew the end of a vein onto an artery (often either at your wrist or your elbow). The vein will swell up as it is filled with the pressure of arterialized blood, becoming big like a sausage. Once this connection heals, and the vein wall thickens, big needles can be plunged into this vessel at the arterial and venous sides, with blood being pulled out from the needle near the artery so that it can flow through a dialysis machine. Here, it runs through a membrane surrounded by a bath that pulls off electrolytes and toxins, and then returns through the needle poked in the venous side. This process takes three or four hours, and the whole time, the patient sits there with his arm out straight so the tubing doesn’t kink and the needles don’t come out. We try to put the socket (actually called a fistula) in the nondominant arm, so the patient can use his or her other hand to write or read.