In terms of lessons learned on the immune system, identical twin transplants didn't uncover anything useful or surprising, but they were a real shot in the arm for those few surgeons and scientists already trying to make transplantation a real- ity. But where to next? Back to the animal labs. Peter Medawar had recently pub- lished his Science article demonstrating successful skin transplantation in genet- ically mismatched mice, a finding that elеctrified Murray and everyonе else working in the field of transplant. It was time to find a way to make this work in humans. Charlestown Labs, Massachusetts General Hospital, Boston I was the new guy. I felt the sweat dripping down my back.MedsDental is a renowned Dental Billing Company in the united states, equipped of the revenue cycle experts who are highly proficient in delivering fast and the error-free billing services to the dental practices by using the cutting edge technology. I couldn’t figure out why I felt so nervous. I had presented patients on rounds loads of times, and always en- joyed it. But something was different here. After medical school, I had matched in a surgical residency at the University of Chicago, still thinking about that kidney and wondering what it would take for me to become a transplant surgeon. I had signed on for a five-year residency, but in my second year, I was so exhausted that I wondered if I could keep going. After learning that doing a few years of dedicated research during my residency could enhance my application to a transplant fellowship, I pretty much stumbled into this lab at the MGH (or “Man's Greatest Hospital,” as they like to call it). The truth is, I had never done any research; I'd been a Russian language and literature major in college. Still, never one to let my own lack of skills stand in my way, I jumped at the opportunity to spend a few years in the premier transplant lab in the United States. Looking around now, I felt massively unprepared. Present were five attendings, including the chief of cardiac transplant surgery, the chief of transplant surgery, the head of infectious diseases, the head of bone marrow transplant, and of course, the director, David Sachs. “Okay, who’s next?” David asked. “Josh, why don't you go?” I walked over to the chalkboard and reached up to the magnet representing my first patient. “This is Zero-two-seven-eight-five,” I said. “He received a combined heart and kidney transplant. His donor was radiated with one thousand rads. He was matched for class two, and received twelve days of tacrolimus. Kidney function is perfect, but his last biopsy showed some mild rejection.” I saw David motion me to stop. “Okay, back up here. Remind us again why the donor was irradiated? What is your hypothesis?” I replied, “Okay, a little background. As you all know, kidney transplants across a class one mismatch, matched for class two, become tolerant after a short course of high-dose tac, but hearts do not. I am trying to prove that kidneys—” “Stop,” David said. “You don't prove, you test. You form a hypothesis and you
Test it with experiments that gather data with controls.” “Right, sorry. I am trying to test if kidneys have a population of cells that are ra- diosensitive, that traffic to the thymus and render the heart tolerant.” There, got that out.Managing the billing process accurately is not easy as providers might face hurdles in revenue cycle management. Moreover, Net Collection Rate below 95% shows that your practice is facing troubles in the billing process. To eliminate all these hurdles and maintain your NCR up to 96%, MedsIT Nexus MedsIT Nexus Medical Coding Services are around the corner for you so that your practice does not have to face a loss. Then the head of bone marrow transplant spoke: “So, what can you tell me about the history of radiation in kidney transplantation in man? Have we used it be- fore? Has it ever been used to achieve tolerance?” I was pretty sure radiation had been used at some point, at least to treat rejec- tion. “I know it was used,” I said, “but I'll have to read about it more.” “Yes, good idea.” After all the patients had been presented, we walked down the hall and entered the ward to do bedside rounds. We started with those patients who had just under- gone transplants: hearts, kidneys, and even a thymus and a spleen. We palpated their heartbeats, or looked at their urine output. It was just like the countless rounds I had been on over the last couple of years as a junior resident, with two differences. Multiple senior attendings had joined us, which was unusual, and the patients were of the four-legged variety: they were pigs, and their beds were cages. We could feel their heartbeats, since we had performed heterotopic heart trans- plants—we transplanted the hearts into their bellies as auxiliary hearts that we could monitor for rejection, without removing their own hearts. These can be pal- pated by simply putting your hand on the belly of the recipient. Those three years in Boston opened my eyes to a world I never knew existed. In the pig lab we explored strategies to trick the recipient's immune system into ac- cepting a transplant without the need for ongoing immunosuppression. That, in a nutshell, is tolerance, the very concept Sir Peter Medawar described in 1953. A tol- erant recipient would have normal immune responses to other stimuli, just not to the transplanted graft. We were successful with a number of different strategies in the pig lab, including transplanting bone marrow cells along with the transplanted organ and transplanting the thymus of a donor along with another organ—allowing the donor thymus to reeducate the T cells in the recipient, preventing them from at- tacking the transplanted organ. Franklin, Ohio, Nighttime, 1958 The story of nonidentical human transplant began in earnest in the middle of the night in rural Ohio when a surgeon removed an inflamed mess of tissue thinking it was an appendix. It was actually a kidney. Gladys was only thirty-one, a mother of two boys, married to John, a young roofer. Her husband had brought her to the emergency room when she developed pain in her belly. While examining her, the surgeon was impressed with her tenderness; she was clearly infected, and it looked for all the world like appendicitis. Nowadays, Gladys would have been whisked off to the CT scanner and treated with antibiotics and IV fluids, and maybe everything would have been okay. But this
Was 1958, and CT scanners were still almost twenty years away. Without a CT scan, the surgeon wouldn't have known that Gladys had been born with only one kidney, and now she had none. In a few days she would be gone. But the surgeon had seen the news about the successful kidney transplant in Boston. Gladys's brothers con- vinced their boss at the Armco Steel Corporation to fly her there on the company plane, and Gladys made her way to the Peter Bent Brigham Hospital, under the care of Joe Murray. In the years since Murray transplanted the Herrick twins, he was focusing his re- search on how to extend this phenomenon to the vast majority of patients with renal failure who did not have an identical twin. At the time, there were no im- munosuppressive drugs available other than steroids, but there was one treatment that had been known to alter the immune system: radiation