|CHRONICLES OF MEDICINE
|Year : 2014 | Volume
| Issue : 2 | Page : 144-149
Tissue and organ transplantation: Myths, miracles, and triumphs
Avneet Singh Chawla1, Ranjan Chandra2, Yatish Agarwal2
1 Department of Surgery, Safdarjung Hospital and Vardhman Mahavir Medical College, New Delhi, India
2 Department of Diagnostic Radiology, Safdarjung Hospital and Vardhman Mahavir Medical College, New Delhi, India
|Date of Web Publication||31-Jul-2014|
Prof. Avneet Singh Chawla
Department of Surgery, Safdarjung Hospital and Vardhman Mahavir Medical College, New Delhi - 110 029
Source of Support: None, Conflict of Interest: None
Notwithstanding the unfulfilled quest for immortality, man's endeavor to outdo organ failure and prolong life has been a journey bejeweled with hues of ingenuity. This exciting odyssey has been marked with chimerical events and miracles in the olden times, and, in the more recent, by triumphs of technical and cognitive advances in organ preservation, surgical skill, immunology, management of infectious diseases, and multidisciplinary innovative approaches, which have collated to fructify the realm of tissue and organ transplantation. The remarkable evolution-colored with serendipitous discoveries, tragic accidents, abandoned paths, and incidents that have produced ethical and legal predicaments-stems from a confluence of cultural, legal, and political acceptance of the need to facilitate organ donation, procurement, and allocation. This serial narrative, punctuated with historic pictures, captures some of the major milestones in the saga of transplant medicine.
Keywords: Bowel transplant, cardiac transplant, cornea transplant, facial transplant, hepatic transplant, organ transplantation, pancreatic transplant, renal transplant, tissue rejection, vascular anastomosis
|How to cite this article:|
Chawla AS, Chandra R, Agarwal Y. Tissue and organ transplantation: Myths, miracles, and triumphs. Astrocyte 2014;1:144-9
The Wondrous Xenotransplant
The idea of replacing diseased or damaged body parts has been around for millennia. Mythological, religious, historical, and archaeological texts are filled with fascinating narratives of organ transplantation. The head and neck xenotransplant on Hindu god Ganesha, born of Parvati, Lord Shiva's consort, is a classic instance. Although Ganesha's elephant-head may purely be mythical, or hide a deeper meaning, still it makes for a most ingenious concept, considering the period when Shiva Purana was inked. Puranic Hindu texts, dating back to 2500-3000 BC, also provide a vivid description of reconstruction of mutilated noses using skin homografts.
The ancient Greek mythology is also packed with tales of gods, heroes, and heraldic beasts with chimerical anatomy and abilities. Evidence for autotransplantation of nonvisceral tissues, such as bone, teeth, and skin, have been described as far back as the prehistoric Bronze Age.
1st century AD
Era of Myths and Miracles
The New Testament of the Bible portrays several instances of homologous transplantation. The account of Jesus of Nazareth restoring a servant's ear severed by Simon Peter's sword in a battle; of Saint Peter reimplanting the breasts of tortured and mutilated Saint Agatha; and of Saint Mark reimplanting a battle-amputated hand of a soldier are all too well known. 
Transplant of a Leg
In Leggenda Aura (Golden Legend of Lives of the Saints, 348 AD), the author Jacques de Voragine vividly recounts the "Miracle of the Black Leg." The accompanying painting portrays the miracle. A Roman deacon Justinian had a gangrenous leg and was in considerable pain. Yet, one morning, he woke up without pain and found himself transplanted with a new leg. This leg was taken from a recently deceased Ethiopian man. 
Coinage of the term Transplant
The great eighteenth century experimentalist John Hunter, who transplanted human teeth and autotransplanted cocks' spurs into their combs, is credited with coining the term "transplant".
The glory of developing the techniques of anastomotic suturing of blood vessels, arterial and venous reconstruction, and cold preservation of harvested organs, goes to French surgeon Alexis Carrel. These techniques were critical from the standpoint of organ transplantation.
Carrel was also a pioneer in giving the theory of biological incompatibility. During the course of his experiments, he could successfully reimplant a kidney in the neck of a dog. A few years later, he carried out renal transplantation and cross-switched the kidneys between two dogs. While working at Rockefeller Institute for Medical Research, USA, he received the Nobel Prize in Medicine in 1912 for his path-breaking work. 
First Successful Corneal Transplant
Ophthalmic surgeon Eduard Konrad Zirm, who did his medical schooling at the University of Vienna, performed the first successful corneal transplant in Olomouc, Moravia on 7 December 1905. He operated on Alois Glogar, a laborer from a small town of Czech Republic. Glogar had been blinded in both eyes a year earlier while slaking lime. The operation and healing were difficult at that time. The operating microscope had not been developed, and hence, the cornea could not be sutured. Zirm successfully used sutures from the outside. 
First Cadaveric Renal Transplants
Russian surgeon Yuri Y Voronoy performed the first cadaveric kidney transplant. He harvested the kidney from a blood group B cadaveric donor who had expired 6 h before, and transplanted the kidney in a uremic O blood type recipient. Unfortunately, the patient survived only 2 days and the transplanted kidney failed to produce any urine. The graft was implanted in the anterior thigh with an ingeniously fashioned ureterocutaneous drain draining the urine. Voronoy tried his hand at cadaveric kidney transplants five more times, yet failed each time because of nonmatching of tissues between the cadaveric donors and recipients.
Sixteen years later, Kuss and Dubost, in Paris, harvested kidneys from convicts executed by guillotine. They also meet with technical surgical success, but the transplantations failed due to immune-mediated allograft failure. 
Understanding of Tissue Rejection
Identifying the immune reactions involved in tissue rejection, British zoologist Peter Medawar working with plastic surgeon Thomas Gibson in the Burn Unit of Glasgow's Royal Infirmary made good the concept that allograft rejection was an immunologic phenomenon with classic properties of sensitization, memory, and tolerance.
Backed by his extensive animal experiments, Peter Medawar demonstrated that the phenomenon of tissue rejection could be suppressed by using immunosuppressive agents. Incidentally, these were the times when Cortisone had just been discovered, and the discovery of azathioprine was round the corner. These molecules gave a major fillip to the emerging field of transplantation.
In the early 1950s, transplant surgeons used total body radiation, steroids, and 6-mercaptopurine for immunosuppression with mixed results. 
Successful Living Renal Transplant
The team of Joseph Murray and John Merrill working at The Peter Bent Brigham Hospital performed the first successful living-related renal transplant between identical twin brothers Ronald and Richard Herrick. The recipient, Richard, had been supported on an artificial kidney machine. The procedure was both a surgical and immunologic success. The recipient survived for 8 years with intact renal allograft function and no evidence of rejection before succumbing to myocardial infarction. 
The same surgical team performed a similar operation between a female twin pair in 1956 with the recipient, Edith Helm, surviving into the 1990s. For his work, Joseph Murray was conferred the Nobel Prize in Medicine in 1990. 
The Big Discovery
The discoveries identifying the major histocompatibility complex (MHC) and human leukocyte antigens (HLA) occurred in the late 1950s. French physician Jean Dausset described the first known leukocyte antigen, now called HLA-A2, in 1958. He received the Nobel Prize in Medicine in 1980 for his work. 
These key discoveries pried open the lid on immune mechanisms and graft rejection; however, they could not be put to wide clinical usage until the 1970s. The breakthrough came with the development of a sensitive and rapid assay, the HLA-cross matching test. 
First Successful Cadaveric Renal Transplant
Joseph Murray and David Hume of The Peter Bent Brigham Hospital, Boston, performed the first successful cadaveric kidney transplant. 
First Hepatic Transplant
Thomas Starzl and his team performed the first liver transplant at the University of Colorado, Denver. However, the patient died in the perioperative period due to overwhelming technical and hemorrhagic complications aggravated by severe portal hypertension and coagulopathy. 
Until the advent of cyclosporine, the long-term survival rates after liver transplantation (LT) remained rather poor, and the 1-year posttransplant survival rates were between 18% and 30%.
First Lung Transplant
James Hardy and his team carried out the first lung transplant in a prison inmate at the University of Mississippi Medical Center, Jackson. The transplant was performed under a serious ethical compromise given that the transplant recipient had the death penalty waived on exchange for agreeing to undergo this experimental surgery. The lung functioned well for 18 days until the patient died due to an acute on chronic renal failure, a previously existing condition. 
First Pancreatic Transplant
WD Kelly, RC Lilliehei, FK Merkel, and Y Idezuki carried out the first pancreas transplant at the University of Minnesota, Minneapolis. This transplant was carried out in combination with those of kidneys in a diabetic patient suffering from terminal renal insufficiency. While the transplanted pancreas only worked for 2 months, good glycemic control was achieved without administration of insulin, which demonstrated the potential role of pancreatic transplant. 
First Cardiac Transplant
Christiaan Barnard carried out the first cardiac transplant at the Groote Schuur Hospital, Cape Town, South Africa in a terminally sick patient of cardiomyopathy, Louis Washkansky. The recipient survived for 18 days.
Christiaan Barnard's second patient, Philip Blaiberg, lived for 19 months. Cardiac transplants are now done across the globe with 5-year survival rates of around 75%. 
First Heart-Lung Transplant
Denton Cooley at the Texas Heart Institute carried out the first heart-lung transplant in 1968. The transplant failed. However, it paved the way for success of Bruce Reitz and Shumway when they restarted heart-lung transplantations using cyclosporine in the 1980s. 
Debut of Cyclosporine
Swiss physician Jean Borel discovered the immunomodulatory properties of cyclosporine in 1977. A patent was filed, and the US FDA gave its approval to the drug Sandimmune in 1983. This was a momentous development in the arena of organ transplantation.
Cyclosporine made a stunning debut. Launched as a part of multidrug immunosuppressive regime, the graft survival rates suddenly took wings and soared following its usage. The 1-year graft survival rates rose to 89% in kidney transplant recipients and 70% in heart and liver transplant recipients. 
First successful Heart-Lung Transplant
Bruce Reitz carried out the first successful heart-lung transplant at Stanford University, California, in a patient with primary pulmonary hypertension. The patient, Mary Gohlke, lived 5 years and co-authored a book, "I'll Take Tomorrow" about her experience. 
Small Intestine Transplant Meets Success
Lillehei carried out the first experimental small intestine transplant in dogs in 1959. However, the work was abandoned due to high rates of morbimortality caused by rejection (the intestine is rich in lymphoid tissue) and sepsis (rupture of the intestinal wall). The first attempts in humans were carried out in the University of Western Ontario (Canada) on two children who received intestine from their mothers with no success. Several other attempts were made across North America, with poor outcomes.
Success finally came to the team of David Grant, William Wall, and Calvin Stiller at London Health Sciences Center, Ontario, Canada in 1988. They carried out a successful multivisceral transplant (liver and the first part of the intestine), and the recipient survived and partook of meals for the next 3 years. 
Living Donor Liver Transplant
The introduction of living donor liver transplantation (LDLT) has been one of the most remarkable steps in the field of LT. Historically, LDLT began as a means for parents of children with severe liver disease to donate a portion of their healthy liver to replace their child's damaged liver. First carried out in 2-year-old Alyssa Smith, who received a portion of her mother's liver in November 1989, the surgery was performed by Christoph Broelsch at the University of Chicago Medical Center.
Its adoption for adults has followed only 10years later. As the demand for LT continues to increase, LDLT provides life-saving therapy for many patients who would otherwise die awaiting a cadaveric organ. In recent years, LDLT has been shown to be a clinically safe addition to deceased donor liver transplantation (DDLT) and has been able to significantly extend the scarce donor pool.
Tacrolimus takes centre stage
Tacrolimus, a new immunosuppressive molecule discovered in 1984, finds approval of the US Food and Drug Administration for use in LT. Tacrolimus is quick to change the outcome in hepatic transplant recipients with cyclosporine-refractory rejection. With its use, approximately 75% such allografts could be rescued. Compared with the precalcineurin immunosuppressive era, calcinreurin-inhibitors transform the graft and patient survival rates in transplant recipients.
The advent of mycophenolate mofetil, sirolimus, and thymoglobulin in the 1990s, and enteric-coated mycophenolate sodium, everolimus, and slow-release tacrolimus in the 2000s has widened the field and enhanced the effectiveness of immunosuppressive molecules.
India passes Transplantation of Human Organs Bill
Based on the draft recommendations formulated by a specially constituted committee under the chair of eminent lawyer L M Singhvi, the parliament of India passed the Transplantation of Human Organs Bill. This bill recognized brain death as a form of death and stated the rules of cadaveric organ transplantation. 
India's first cardiac transplant
Cardiac surgeon P Venugopal at the All India Institute of Medical Sciences, New Delhi, performed India's first heart transplant on August 3, 1994. The recipient was a 47-year-old male patient afflicted with severe cardiomyopathy, while the donor was a 35-year-old brain-dead female who had suffered a cerebral hemorrhage.
India's first cadaveric liver transplant
The first successful cadaveric liver transplant in India was performed at Apollo Hospitals, Chennai by a transplant surgeon from Singapore in 1998. This was followed soon by a cadaver transplant and a living related transplant in the Indraprastha Apollo Hospitals, New Delhi. Since 2004, a number of centers in the country are doing cadaveric and LDLT successfully. 
The world's first successful partial face transplant was carried out by the team of Bernard Devauchelle, an oral and maxillofacial surgeon, Benoit Lengelé, a Belgian plastic surgeon, and Jean-Michel Dubernard in Amiens, France on November 27, 2005. The surgery was performed on Isabelle Dinoire, who had been mauled by her black Labrador Retriever. A triangle of face tissue from a brain-dead woman's nose and mouth was grafted onto the patient. On December 13, 2007, the first detailed report of the progress of this transplant after 18 months was released in the New England Journal of Medicine.  The patient was happy with the results but had found the journey very difficult, especially with respect to her immune system's response.
Since this first facial transplant, 28 more facial transplants have been done worldwide with encouraging immunological, functional, psychological, and aesthetic outcomes.
Transplant of a bioengineered trachea
Professor Paolo Macchiarini and his team performed the first tissue-engineered tracheal transplant at the Hospital Clínic, University of Barcelona, Spain. Adult stem cells were harvested from the patient's bone marrow, grown into a large population, and matured into chondrocytes. The team seeded the newly grown chondrocytes, as well as epithelial cells, into a decellularized tracheal segment taken from a 51-year-old donor who had died of cerebral hemorrhage.
Notification of Transplantation of Human Organs Act, 2011
The union government notified the Transplantation of Human Organs Act, 2011. This new act approved by both houses of parliament and the President of India in 2011 holds twin key objectives: one, to curb commercial sale of human organs in India; and two, to encourage families to donate organs of their brain-dead loved ones.
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