History of organ transplantation

Successful human allotransplants have a relatively long history of operative skills that were present long before the necessities for post-operative survival were discovered. Rejection and the side effects of preventing rejection (especially infection and nephropathy) were, are, and may always be the key problem.
Several apocryphal accounts of transplants exist well prior to the scientific understanding and advancements that would be necessary for them to have actually occurred. The Chinese physician Pien Chi'ao reportedly exchanged hearts between a man of strong spirit but weak will with one of a man of weak spirit but strong will in an attempt to achieve balance in each man. Roman Catholic accounts report the 3rd-century saints Damian and Cosmas as replacing the gangrenous leg of the Roman deacon Justinian with the leg of a recently deceased Ethiopian. Most accounts have the saints performing the transplant in the 4th century, many decades after their deaths; some accounts have them only instructing living surgeons who performed the procedure.
The more likely accounts of early transplants deal with skin transplantation. The first reasonable account is of the Indian surgeon Sushruta in the 2nd century BC, who used autografted skin transplantation in nose reconstruction rhinoplasty. Success or failure of these procedures is not well documented. Centuries later, the Italian surgeon Gasparo Tagliacozzi performed successful skin autografts; he also failed consistently with allografts, offering the first suggestion of rejection centuries before that mechanism could possibly be understood. He attributed it to the "force and power of individuality" in his 1596 work De Curtorum Chirurgia per Insitionem.

The first successful corneal allograft transplant was performed in 1837 in a gazelle model; the first successful human corneal transplant, a keratoplastic operation, was performed by Eduard Zirm at Olomouc Eye Clinic, now Czech Republic, in 1905. The first transplant in the modern sense - the implantation of organ tissue in order to replace an organ function - was a thyroid transplant in 1883. It was performed by the Swiss surgeon and later Nobel laureate Theodor Kocher. In the preceding decades Kocher had perfected the removal of excess thyroid tissue in cases of goiter to an extent that he was able to remove the whole organ without the patient dying from the operation. Kocher carried out the total removal of the organ in some cases as a measure to prevent recurrent goiter. By 1883 the surgeon noticed that the complete removal of the organ leads to a complex of particular symptoms that we today have learned to associate with a lack of thyroid hormone. Kocher reversed these symptoms by implanting thyroid tissue to these patients and thus performed the first organ transplant. In the following years Kocher and other surgeons used thyroid transplantation also to treat thyroid deficiency that had appeared spontaneously, without a preceding organ removal. Thyroid transplantation became the model for a whole new therapeutic strategy, organ transplantation. After the example of the thyroid other organs were transplanted in the decades around 1900. Some of these transplants were done in animals for purposes of research, where organ removal and transplantation became a successful strategy of investigating the function of organs.

Kocher was awarded his Nobel Prize in 1909 for the discovery of the function of the thyroid gland. At the same time, organs were also transplanted for treating diseases in humans. The thyroid gland became the model for transplants of adrenal and para-thyroid glands, pancreas, ovary, testicles and kidney. By 1900 the idea that one can successfully treat internal diseases by replacing a failed organ through transplantation had been generally accepted.[5] Pioneering work in the surgical technique of transplantation was made in the early 1900s by the French surgeon Alexis Carrel, with Charles Guthrie, with the transplantation of arteries or veins. Their skilful anastomosis operations, the new suturing techniques, laid the groundwork for later transplant surgery and won Carrel the 1912 Nobel Prize in Physiology or Medicine. From 1902 Carrel performed transplant experiments on dogs. Surgically successful in moving kidneys, hearts and spleens, he was one of the first to identify the problem of rejection, which remained insurmountable for decades. The discovery of transplant immunity by the German surgeon Georg Schöne, various strategies of matching donor and recipient, and the use of different agents for immune suppression did not result in substantial improvement so that organ transplantation was largely abandoned after WWI.[5]

Major steps in skin transplantation occurred during the First World War, notably in the work of Harold Gillies at Aldershot. Among his advances was the tubed pedicle graft, maintaining a flesh connection from the donor site until the graft established its own blood flow. Gillies' assistant, Archibald McIndoe, carried on the work into the Second World War as reconstructive surgery. In 1962 the first successful replantation surgery was performed – re-attaching a severed limb and restoring (limited) function and feeling.
The first attempted human deceased-donor transplant was performed by the Ukrainian surgeon Yuri Voronoy in the 1930s;[6][7] rejection resulted in failure. Joseph Murray and J. Hartwell Harrison performed the first successful transplant, a kidney transplant between identical twins, in 1954, successful because no immunosuppression was necessary in genetically identical twins.
In the late 1940s Peter Medawar, working for the National Institute for Medical Research, improved the understanding of rejection. Identifying the immune reactions in 1951 Medawar suggested that immunosuppressive drugs could be used. Cortisone had been recently discovered and the more effective azathioprine was identified in 1959, but it was not until the discovery of cyclosporine in 1970 that transplant surgery found a sufficiently powerful immunosuppressive.

Dr. Murray's success with the kidney led to attempts with other organs. There was a successful deceased-donor lung transplant into a lung cancer sufferer in June 1963 by James Hardy in Jackson, Mississippi. The patient survived for eighteen days before dying of kidney failure. Thomas Starzl of Denver attempted a liver transplant in the same year but was not successful until 1967.
The heart was a major prize for transplant surgeons. But over and above rejection issues, the heart deteriorates within minutes of death, so any operation would have to be performed at great speed. The development of the heart-lung machine was also needed. Lung pioneer James Hardy attempted a human heart transplant in 1964, but when a premature failure of the recipient's heart caught Hardy with no human donor, he used a chimpanzee heart, which failed very quickly. The first success was achieved on December 3, 1967, by Christiaan Barnard in Cape Town, South Africa. Louis Washkansky, the recipient, survived for eighteen days amid what many[who?] saw as a distasteful publicity circus. The media interest prompted a spate of heart transplants. Over a hundred were performed in 1968–69, but almost all the patients died within sixty days. Barnard's second patient, Philip Blaiberg, lived for 19 months.

It was the advent of cyclosporine that altered transplants from research surgery to life-saving treatment. In 1968 surgical pioneer Denton Cooley performed seventeen transplants, including the first heart-lung transplant. Fourteen of his patients were dead within six months. By 1984 two-thirds of all heart transplant patients survived for five years or more. With organ transplants becoming commonplace, limited only by donors, surgeons moved on to riskier fields, including multiple-organ transplants on humans and whole-body transplant research on animals. On March 9, 1981, the first successful heart-lung transplant took place at Stanford University Hospital. The head surgeon, Bruce Reitz, credited the patient's recovery to cyclosporine-A.

As the rising success rate of transplants and modern immunosuppression make transplants more common, the need for more organs has become critical. Transplants from living donors, especially relatives, have become increasingly common. Additionally, there is substantive research into xenotransplantation, or transgenic organs; although these forms of transplant are not yet being used in humans, clinical trials involving the use of specific cell types have been conducted with promising results, such as using porcine islets of Langerhans to treat type 1 diabetes. However, there are still many problems that would need to be solved before they would be feasible options in patients requiring transplants.
Recently, researchers have been looking into means of reducing the general burden of immunosuppression. Common approaches include avoidance of steroids, reduced exposure to calcineurin inhibitors, and other means of weaning drugs based on patient outcome and function. While short-term outcomes appear promising, long-term outcomes are still unknown, and in general, reduced immunosuppression increases the risk of rejection and decreases the risk of infection.
Many other new drugs are under development for transplantation.[8]
The emerging field of regenerative medicine promises to solve the problem of organ transplant rejection by regrowing organs in the lab, using the patients' own cells (stem cells or healthy cells extracted from the donor site.)

Timeline of successful transplants
1905: First successful cornea transplant by Eduard Zirm (Czech Republic)
1950: First successful kidney transplant by Dr Richard H. Lawler (Chicago, U.S.A)[9]
1966: First successful pancreas transplant by Richard Lillehei and William Kelly (Minnesota, U.S.A.)
1967: First successful liver transplant by Thomas Starzl (Denver, U.S.A.)
1967: First successful heart transplant by Christian Barnard (Cape Town, South Africa)
1981: First successful heart/lung transplant by Bruce Reitz (Stanford, U.S.A.)
1983: First successful lung lobe transplant by Joel Cooper (Toronto, Canada)
1984: First successful double organ transplant by Thomas Starzl and Henry T. Bahnson (Pittsburgh, U.S.A.)
1986: First successful double-lung transplant (Ann Harrison) by Joel Cooper (Toronto, Canada)
1995: First successful laparoscopic live-donor nephrectomy by Lloyd Ratner and Louis Kavoussi (Baltimore, U.S.A.)
1997: First successful allogeneic vascularized transplantation of a fresh and perfused human knee joint by Gunther O. Hofmann
1998: First successful live-donor partial pancreas transplant by David Sutherland (Minnesota, U.S.A.)
1998: First successful hand transplant by Dr. Jean-Michel Dubernard (Lyon, France)
1999: First successful Tissue Engineered Bladder transplanted by Anthony Atala (Boston Children's Hospital, U.S.A.)
2005: First successful ovarian transplant by Dr P N Mhatre (Wadia hospital Mumbai, India)
2005: First successful partial face transplant (France)
2006: First jaw transplant to combine donor jaw with bone marrow from the patient, by Eric M. Genden Mount Sinai Hospital, New York
2006: First successful human penis transplant (later reversed after 15 days due to 44 year old recipient's wife's psychological rejection) (Guangzhou, China) [10][11]
2008: First successful complete full double arm transplant by Edgar Biemer, Christoph Höhnke and Manfred Stangl (Technical University of Munich, Germany)
2008: First baby born from transplanted ovary by James Randerson
2008: First transplant of a human windpipe using a patient’s own stem cells, by Paolo Macchiarini (Barcelona, Spain)
2008: First successful transplantation of near total area (80%) of face, (including palate, nose, cheeks, and eyelid) by Maria Siemionow (Cleveland, USA)
2010: First full facial transplant, by Dr Joan Pere Barret and team (Hospital Universitari Vall d'Hebron on July 26, 2010 in Barcelona, Spain.)
2011: First double leg transplant, by Dr Cavadas and team (Valencia's Hospital La Fe, Spain)

Liver transplantation history
The liver has been the noble organ, the organ of life from time immemorial - liver in English, Leber in German, derived from the verb to live.
Liver transplantation was first attempted in dogs by Welch in Albany in 1955 and Cannon in California in 1956. The first human liver transplant was performed in 1963 by a surgical team led by Dr. Thomas Starzl of Denver, Colorado, United States. The three-year-old child with biliary atresia, in a disastrous physiological condition, received the liver from another child who had died from a brain tumor. The recipient survived for five hours after the transplantation, succumbing to the complications of coagulation and haemostasis encountered during the operation. The second liver transplant in man was performed on May 5, 1963, was more successful, although the patient died on the 22nd postoperative day from pulmonary embolism but with a normal liver. Dr. Starzl performed several additional transplants over the next few years before the first short-term success was achieved in 1967 with the first one-year survival post transplantation.

Despite the development of viable surgical techniques, liver transplantation remained experimental through the 1970s, with one year patient survival in the vicinity of 25%.The introduction of cyclosporin by Sir Roy Calne markedly improved patient outcomes, and the 1980s saw recognition of liver transplantation as a standard clinical treatment for both adult and pediatric patients with appropriate indications. A further advance was the improvement of liver preservation by the introduction of University of Wisconsin Solution (Viaspan) in 1987 extending periods of cold storage in Collins solution by two to three fold. Liver transplantation is now performed at over one hundred centers in the USA, as well as numerous centers in Europe and elsewhere. One-year patient survival is 80–85%, and outcomes continue to improve, although liver transplantation remains a formidable procedure with frequent complications. However, the supply of liver allografts from non-living donors is far short of the number of potential recipients, a reality that has spurred the development of living donor liver transplantation.

Lung transplantation history
James Hardy, MD, and Watts Webb, MD, performed the first human lung transplant at the University of Mississippi Medical Center in 1963. The patient, a 58-year-old man suffering from end-stage emphysema and lung cancer, died 18 days later.
The 1960s and 1970s saw a number of additional unsuccessful attempts at human lung transplantation. The modern era of lung transplantation was launched in 1983 when Dr. Joel Cooper and his associates at the University of Toronto successfully transplanted two patients with idiopathic pulmonary fibrosis. The success of Dr. Cooper and his team stemmed in part from their understanding of how to protect the vulnerable bronchial anastomosis (bronchial "hookup").
The team also pioneered new surgical techniques, contributing to the evolution of the lung transplant procedure.
Since the initial transplant era, further development of surgical techniques and new medications have led to increasingly-successful outcomes for transplant patients. Medications such as cyclosporin and tacrolimus lower the risk of organ rejection. Antimicrobial agents such as ganciclovir and valganciclovir more effectively help prevent or treat infections. Clinicians understand better how to deal with complications such as donor graft dysfunction and chronic rejection. Improved donor management, expanded donor criteria, and improved preservation techniques have also played a role in lung transplantation's growing success.
Today lung transplantation is a widely-accepted therapeutic option for a growing number of end-stage lung diseases. Continued development of new transplant medications furthers the science of transplantation and brings with it new hope and optimism for thousands of people who will benefit from this life-saving surgery.
The first successful transplant surgery involving the lungs was a heart-lung transplant, performed by Dr. Bruce Reitz of Stanford University on a woman who had idiopathic pulmonary hypertension.
•  1983: First successful long-term single lung transplant (Tom Hall) by Joel Cooper (Toronto)
•  1986: First successful long-term double lung transplant (Ann Harrison) by Joel Cooper (Toronto)
•  1988: First successful long-term double lung transplant for cystic fibrosis by Joel Cooper (Toronto)

Heart transplantation history
The history of heart surgery, spanning only 100 years to date, has seen some of the most daring and persistent men and women in all of medical history. Many aspects of heart surgery, including such innovations as the heart-lung machine, aortic aneurysm surgery, and the correction of congenital heart defects, have provided future surgeons with an important lesson: diligent research can solve complex problems. The history and development of cardiac transplantation is particularly full of challenges that have been overcome, with the research phase alone spanning more than 90 years. During that time, essential contributions came from all over the world, including the United States, Russia, England, and South Africa. As is typical of medical advancement, individual contributions did not stand alone but added to the experience of those who had come before. Even so, the work of a few particular groups deserves special recognition. Most notable is the Stanford team, led by Dr. Norman Shumway, who continued to transplant human hearts when other institutions had abandoned hopes for the operation. Largely because of the commitment of that team, cardiac transplantation has become a standard option in the treatment of end-stage heart disease. Currently, only the availability of donor hearts limits the number of cardiac transplantations performed worldwide.

By the 1960s, surgeons were ready to tackle hearts too far gone for repair. In 1964, a team of surgeons in Jackson, Miss., performed the first animal-to-human heart transplant on record, placing a chimpanzee's heart into a dying man's chest. It beat for an hour and a half but proved too small to keep him alive, a failure that revealed surgeons would have to use human hearts if transplants were to achieve enduring success.
First Heart Transplant (1967): On December 3, 1967, South African surgeon Christiaan Barnard conducted the first heart transplant on 53-year-old Lewis Washkansky. The surgery was a success. However, the medications that were given to Washkansky to prevent his immune system from attacking the new heart also supressed his body's ability to fight off other illnesses. Eighteen days after the operation, Washkansky died of double pneumonia.

In 1984, the world's first successful pediatric heart transplant was performed at Columbia on a four-year-old boy. He received a second transplant in 1989 and continues to live a productive life today.
In the 1970s, the development of better anti-rejection drugs made transplantation more viable. Dr. Barnard continued to perform heart transplant operations, and by the late 1970s many of his patients were living up to five years with their new hearts. Successful heart transplant surgery continues to be performed today, but finding appropriate donors is extremely difficult.

Kidney transplant history
The French surgeon Mathieu Jaboulay (1860-1913), also in Lyon, was the first to clearly document kidney transplants from animals to humans. In 1906, he transplanted the left kidney of a pig into the left elbow of a woman suffering from nephrotic syndrome (Jaboulay,1906). This is considered the first human renal transplant, a xenotransplant. However, the graft failed because of early vascular thrombosis
Three years later, in 1909, Ernest Unger (1875-1938) in Berlin transplanted a monkey kidney into a girl dying of renal failure; no urine was produced, and Unger concluded that the biochemical barrier was insoluble (Unger, 1909).

1936: First Human Transplants
Working in some obscurity, Yu Yu Voronoy (in Kherson, Ukraine) performed six human kidney allografts between 1933 and 1949 - the kidneys being transplanted into the thigh. The first 'successful' one, in 1933, was the first transplanted human kidney (Voronoy, 1937; Hamilton, 1984).  The recipient was a 26-year old woman who was admitted in a uraemic coma after swallowing mercury chloride in a suicide attempt. Voronoy retrieved the kidney from a 60-year-old man who had died from a fracture of the base of the skull. The donor had been dead for 6 hours. The kidney was ABO-incompatible (B to O). The recipient died 48 hours later without making urine but the vessels were patent at autopsy 2 days later. In the six transplants he reported, no significant renal function occurred in any of them.

Sporadic further efforts at renal allotransplantation were made in the ensuing 15 years without effective immunosuppression, as documented by Groth (1972) and Hume and Merrill (1935).

1945-1953: First Successful Renal Transplants
It is difficult to state who did the first successful renal transplant. That honour could go the following three pioneers in 1945, at the Peter Bent Brigham Hospital in Boston: Charles Hufnagel (staff surgeon), Ernest Landsteiner (chief resident in urology) and David Hume (1917-1973; assistant surgical resident) . Landsteiner was the son of Karl Lansteiner, Nobel prize winner, who developed the modern system of classification of blood groups.
As dialysis was not yet available, they decided to try to save her life by performing a kidney transplant; obtaining a kidney from an elderly patient who had just died during surgery. They wheeled a 29 year old woman, with acute renal failure, to the treatment room at the end of the hall; and, using two gooseneck lamps for light, attached the donor kidney to the woman’s antecubital vessels, so that it rested outside the skin. They then covered the kidney with a plastic bag and watched as the patient’s urine drained into a jar. This primitive transplant lasted only four days, and she recovered renal function, surviving to be discharged. This may have been the first (albeit perhaps not entirely necessary) 'successful' deceased donor transplant, outside the abdomen.

David Hume (1917-1973), Boston
Five years later, in 1950, the first success intra-abdoeminal cadaveric renal transplant occurred in a patient with CKD. It was carried out on 17th June, by Richard Lawler (1895-1982) in Chicago. He removed a kidney from a patient with cirrhosis who had died of liver disease, and placed it into his patient, Ruth Tucker (44 years), who had polycystic kidney disease (removing one of them at the same time) (Lawler, 1950). The operation occured at the Little Company of Mary Hospital, Chicago. Lawler said of the donor, “Not the most ideal patient, but the best we could find,” in an interview after the surgery.

Richard H Lawler (1896-1982), Chicago
To everyone's surprise, the kidney worked for at least 53 days. At ten months, it was found to be shrunken, discoloured and rejected, and was removed. The patient lived for another five years. Enduring both notoriety and sometimes vociferous censure by his peers, Lawler never performed another transplant. He was besieged with letters from doctors wanting to learn from him and from patients seeking his services. But he never performed another kidney transplant, saying in 1979, ''I just wanted to get it started''. Lawler was assisted by: James West, who later went on to study alcoholism as a disease and launch the Betty Ford Clinic (of which he later became Medical Director), and Raymond Murphy. They were assisted by nurses including: Mary Lou Zidek, who assisted the anesthesiologist during the surgery; and Nora O’Malley, who was the scrub nurse.

In the 1950s and early 60s a group of French transplant surgeons (who became known as the 'French Transplantation Club') carried out a series of important achievements. In a historic 12 day period in January 1951, René Küss and Charles Dubost (in Paris) and Marceau Servelle (Strasbourg) performed the first renal transplants in France; and first used the extraperitoneal renal transplantation procedure which is in common use today - called the 'Küss Procedure'. Dubost and Servelle obtained their renal allografts from the same guillotined convict donor, whereas R. Küss used a kidney that had been removed from another patient for therapeutic purpose. A total of nine patients were transplanted, all nine patients rejected their grafts. In Rene Kuss' famous publication in Mem Acad Chir (1951) he stated "about some cases of renal allograft in human .. in the present state of knowledge, the only rational basis for kidney replacement would be between monozygotic twins". Clearly the concept of an immune related rejection was well established at this point.

in 1951, Gordon Murray (1894-1976) in Toronto, performed a series of 4 deceased donor kidney transplants using his heterotopic technique (Murray, 1954). The team included nurse Rita Smith, anaesthetist Stephen Evelyn, and resident William Lougheed. Both the deceased donor and the prospective recipient were operated on in the same room, Operating Room “C” at the Toronto General Hospital, separated by a screen. Of the first 3 recipients, the longest survivor lived 12 days, with urine production and improvement in serum biochemistry.

On May 2nd, 1952, Murray’s fourth patient was a 26-year-old woman who had been diagnosed with Bright’s disease, 18 months previously. The patient made a spectacular recovery with loss of oedema. The patient remained well for at least the next 21 years and the kidney was never removed. In his report to this journal, Murray admitted that while “this patient might have returned to this sort of good health independently,” he remained convinced of the importance of the transplant in achieving that state. This may have been the first long term success in renal transplantation.

1954-60: Boston and Murray
The only examples of probable allograft function through 1954 were provided first by one of the non-immunosuppressed patients of Hume whose graft in the thigh location functioned for 5 months (Hume, 1955). Hume's career lasted well into the next era of transplantation, until his death in May, 1973, near Los Angeles in the crash of a private plane. John Merrill drowned off the beach of a Caribbean island in 1984.

The next important milestone in the history of renal transplantation, occurred two days before Christmas in 1954. Something happened at the Peter Bent Brigham Hospital that was to change the course of renal transplantation. Richard Herrick, a 24 year-old patient with chronic kidney disease and severe hypertension secondary to glomerulonephritis and an identical twin, Ronald, had been referred to the Brigham by his physician, David C Miller. On December 23rd 1954, a kidney was removed from Ronald by the urologist J Hartwell Harrison and transplanted by Joseph E Murray into the pelvic location of the donor's identical twin brother, Richard (Murray, 1955). The nephrologist was John P Merrill.  The vascular anastamosis was completed at 11.15am, and the operation lasted 5 and half hours.

As in the earlier mother-to-son transplant in France, no effort was made to preserve the isograft; but nonetheless, it functioned promptly despite 82 minutes of warm ischaemia. The kidney lasted for 8 years, when Richard Herrick died of a myocardial infarction, his glomerulonephritis having recurred. According to Merrill, the bold step of exploiting the principle of genetic identity for whole organ transplantation had been suggested by the recipient's physician, David C Miller, of the Public Health Service Hospital, Boston (Merrill, 1956). This was the first longterm success in living renal transplantation.
Soon after the success in Boston, progress started in the UK. The first deceased donor transplant (unsuccessful) was performed in the UK in 1955, at St Marys Hospital. This was carried out by Charles Rob (1913-2001) and William James 'Jim' Dempster (1918 - 2008; from the Hammersmith) (Joekes, 1957).

In 1959, Gordon Murray (Toronto) carried out the first successful non-twin sibling transplant. Again in 1959, Joseph Murray demonstrated that sublethal total body irradiation (TBI) could be used successfully, in the first non-identical (fraternal) twin transplant in the USA (Merrill, 1960). In January 1960, the first successful living kidney transplant between non-twin siblings in France took place at the Foch Hospital in Surenes, France - performed by a team led by René Küss (Kuss, 1962).

Progress was also occurring in the UK. In July 1959 the first successful deceased donor renal transplant in the UK was performed by 'Fred' Peter Raper, a urologist, in Leeds. The team in Leeds used cyclophosphamide as an immunosuppression. The patient died, with a working transplant eight months later, of a viral infection. On 30th October, 1960, the first successful living kidney transplant in UK was performed on identical twins. Sir Michael Woodruff (1911-2001) operated on the patient, a 49 year old man; and Mr James A Ross, on the donor (Woodruff, 1961). The patient had been referred on 15th September, 1960, by Dr RF Robertson with advanced CKD, from Leith Hospital to the Royal Infirmary of Edinburgh. Following these successful operations, the donor resumed work 3 weeks after the operation; the patient returned to work after 15 weeks. The patient lived for a further 6 years before dying from an unrelated disease.

History of Tissue Transplantation
•    1900s - Successful transplantation of bone, soft tissue and corneas began.
•    1949 - The establishment of the U.S. Navy Tissue Bank gave the nation its first bone and tissue processing and storage facility.
•    1970s -The rapid development of transplant medicine, combined with factors including general population growth and expansion of the elderly population caused an increased demand for donated tissues and organs.
•    1986 - There were more than 300 bone banks in operation.
•    1993 - The Food and Drug Administration (FDA) initiated regulation of all U.S. Tissue Banks.
•    1997-2005 - Additional regulations were announced including the required registration with the FDA of all tissue banking establishments and tissue donor suitability criteria.
o    The FDA enforced the comprehensive Good Tissue Practices. This regulation which binds all agencies that recover, process, store, label, package, distribute, screen or test human tissue resulted in greater safety assurances industry wide.
o    Today - It is estimated that over one million allograft tissue transplants are performed annually.
•    Allografts are utilized in almost all surgical disciplines including:
•    orthopedics
•    neurosurgery
•    gynecology
•    cardiac surgery
•    burn care and many others.
•    Over time, physicians have realized the benefits of using allograft tissues over the alternatives such as autografts and synthetics.

History of immune suppression

1960-65: Age of Imunosuppression
In November 1960 the first successful non-twin sibling living transplant in the UK was carried out by Hopewell.  'Success' was difficult to define in these early transplants. This patient died after seven weeks. Also in 1960, Willard Goodwin, at the University of California in Los Angeles, started using corticosteroids as a further adjunct to the treatment (Goodwin, 1963). Further work on immunosuppression was clearly necessary.

The next big step occurred in 1962, when Calne and Murray first used azathioprine (a drug related to 6MCP) as an immunosuppressant (Calne, 1962). Murray's team, in Boston, started using azathioprine, initially with poor results. However, their third azathioprine-treated patient, who received a deceased donor transplant in April 1962, did significantly better. He survived over one year and was the USA's first deceased donor renal allograft (Murray, 1963) with long term survival. This followed Gordon Murray's original success in Canada in 1952. That Joseph Murray considered a year of life a success is a useful background to a conference later on that year. In 1963, Thomas Starzyl first used prednisolone and azathioprine from the start of a transplant, with success; ushering in a new era of effective 'dual therapy' in transplantation. Starzyl was to go on to carry out the world's first liver transplant in the same year. Calne also went on to pioneer the use of ciclosporin in renal transplantation (Calne, 1978).

Keith Reemtsma (1925-2000) was the first to show that non-human organs could be transplanted to humans and function for a significant period of time. In 1963 and 1964, at Tulane University in New Orleans, Reemtsma, gave chimpanzee kidneys to 5 patients in the first chimpanzee-to-human transplants. The recipients died (of infection) from 8 to 63 days after receiving a chimpanzee kidney. Then, in 1964Reemtsma transplanted a kidney from a chimpanzee to a 23-year-old teacher. She lived with it for 9 months until succumbing to overwhelming infection.

Late in 1963, all available information was discussed at a conference near Washington DC (Murray, 1964). About twenty-five active participants gathered in a small, hot room, in an old building at the National Institutes of Health. Thirteen teams - two from France, five from the UK, and six from the USA - presented their overall findings from 216 recipients of renal allografts. The results were not good. 52% of all those receiving grafts from related donors had died, and 81% of those with kidneys from unrelated or cadaveric donors. Joseph Murray concluded, "Although the beginnings of clinical success are apparent, strong reservations must be kept in mind regarding the ultimate fate of these pateints. Kidney transplantation is still highly experimental and not yet a therapeutic procedure".

Nonetheless, teams continued their research, and progress was rapid. By 1965, one year survival rates of allografted kidneys from living related donors were approaching 80%, and from cadavers 65% (Murray JE, Nobel Lecture, 1990); accepting that there was a substantial death rate and no return to dialysis. It is interesting that one year graft survival rates are not that different in the modern age (95% and 85% respectively). Surgical techniques are largely the same as in this pioneering period (1943-1965). So, indefinite functioning of transplanted organs with little/no immunosuppression (with all its complications) remains the target for future generations. In other words, the non-surgical components of organ transplantation - immunosuppression, tissue matching, and organ procurement (and preservation) - have not yet delivered excellence in the 21st Century.

Hand transplantation history
A hand transplant was performed in Ecuador in 1964, but the patient suffered from transplant rejection after only two weeks.
The first short-term success in human hand transplant occurred with New Zealander Clint Hallam who had lost his hand in an accident while in prison. The operation was performed on September 23, 1998 in Lyon, France by a team assembled from different countries around the world including Prof Nadey Hakim who represented the UK, and Professor Jean-Michel Dubernard from France. A microsurgeon on the team, Dr. Earl Owen from Australia, was privy to the detailed basic research, much of it unpublished, that had been carefully gathered by the team in Louisville. After the operation, Hallam wasn't comfortable with the idea of his transplanted hand and failed to follow the prescribed post-operative drug and physiotherapy. His inaccurate expectations became a vivid example of the necessity of a fully committed team of caregivers, including psychologists, that can correctly select and prepare the potential transplant recipients for the lengthy and difficult recovery and for the modest functional restoration of a transplanted hand to be expected. Hallam's transplanted hand was removed at his request by the transplant surgeon Nadey Hakim on February 2, 2001 following another episode of rejection.

The first hand transplant to achieve prolonged success was directed by a team of Kleinert Kutz Hand Care surgeons including Drs. Warren C. Breidenbach and Tsu-Min Tsai in cooperation with the Christine M. Kleinert Institute, Jewish Hospital and the University of Louisville in Louisville, Kentucky. The procedure was performed on New Jersey native Matthew Scott on January 24, 1999. Scott had lost his hand in a fireworks accident at age 24. Later in 1999, the Philadelphia Phillies baseball team asked him to do the honors of throwing out the ceremonial first pitch. The Louisville group went on to perform the first five hand transplants in the United States and have performed nine hand transplants in eight recipients as of 2008.

In contrast to the earlier attempts at hand transplantation, the Louisville group had performed extensive basic science research and feasibility studies for many years prior to their first clinical procedure {for example, Shirbacheh et al., 1998}. There also was considerable transparency and institutional review board oversight involved in the screening and selection of prospective patients.
In March 2000, a team of surgeons at the University of Innsbruck in Austria began a series of three bilateral hand transplants over six years. The first was an Austrian police officer who had lost both hands attempting to defuse a bomb. He has completed an around-the-world solo motorcycle trip using his transplanted hands.

University of Louisville doctors also performed a successful hand transplant on Michigan native Jerry Fisher in February 2001, and Michigan resident David Savage in 2006.[1]
On January 14, 2004, the team of Professor Jean-Michel Dubernard (Edouard-Herriot Hospital, France) declared a five-year-old double hand transplant a success. The lessons learned in this case, and in the 26 other hand transplants (6 double) which occurred between 2000 and 2005, gave encouragement to other transplant operations of such organs as the face, abdominal wall or larynx.
On May 4, 2009 Jeff Kepner, a 57-year-old Augusta, Georgia, resident, underwent the first double hand transplant in the United States at the University of Pittsburgh Medical Center by a team led by Dr. W.P. Andrew Lee, who also had been performing careful basic research on such transplants for many years. A CNN story on his follow up demonstrated the limited functional restoration to be expected, particularly following bilateral transplantation.

On February 18, 2010 the first female in the United States underwent hand transplantation at Wilford Hall Medical Center in San Antonio, Texas. The procedure was performed by surgeons from The Hand Center of San Antonio and US Air Force.
On June 22, 2010, a Polish soldier received two new hands from a female donor, after losing them three years earlier while saving a young recruit from a bomb.

On March 8, 2011, 26-year-old Emily Fennell underwent an 18 hour surgery to attach a right hand. This was performed in the Ronald Reagan UCLA Medical Center.

March, 12 2011 Linda Lu became the recipient of the first hand transplant in the Southeast, performed at Emory University Hospital, from a donor “Leslie Sullivent”.

In the fall of 2011, 28-year-old Lindsay Ess received a double hand transplant at the Hospital of the University of Pennsylvania in an 11 1/2 hour surgery.

On February 27, 2013, 38-year-old Eskandar Moghaddami received first hand transplant surgery by the 15 Khordad Hospital plastic surgery team in Iran, Tehran(Head of team:Dr Abdoljalil Kalantar-Hormozi,professor of plastic surgery,Shahid Beheshti university of medical sciences).
Although the one-year survival rate of transplanted hands has been excellent at institutions that are fully committed to the procedure, the number of hand transplants performed after 2008 has been small due to drug-related side effects, uncertain long-term outcome, and the high costs of surgery, rehabilitation and immunosuppression (Schneeberger et al., 2008)

Face transplant history

Self as donor ("face replant")
The world's first full-face replant operation was on nine-year-old Sandeep Kaur, whose face was ripped off when her hair was caught in a thresher. Sandeep's mother witnessed the accident. Sandeep arrived at the hospital unconscious with her face in two pieces in a plastic bag. An article in The Guardian recounts: "In 1994, a nine-year-old child in northern India lost her face and scalp in a threshing machine accident. Her parents raced to the hospital with her face in a plastic bag and a surgeon managed to reconnect the arteries and replant the skin." The operation was successful, although the child was left with some muscle damage as well as scarring around the perimeter where the facial skin was sutured back on. Sandeep's doctor was Abraham Thomas, one of India's top microsurgeons. In 2004, Sandeep was training to be a nurse.
In 1996, a similar operation was performed in the Australian state of Victoria, when a woman's face and scalp, torn off in a similar accident, was packed in ice and successfully reattached.

Partial face transplant
The world's first partial face transplant on a living human was carried out on 27 November 2005 by Bernard Devauchelle, an oral and maxillofacial surgeon, and Jean-Michel Dubernard in Amiens, France. Isabelle Dinoire underwent surgery to replace her original face, which had been mauled by her black Labrador dog. A triangle of face tissue from a brain-dead human's nose and mouth was grafted onto the patient. On 13 December 2007, the first detailed report of the progress of this transplant after 18 months was released in the New England Journal of Medicine and documents that the patient was happy with the results but also that the journey has been very difficult, especially with respect to her immune system's response.
In April 2006, Dr Guo Shuzhong at the Xijing military hospital in Xian, China similarly transplanted the cheek, upper lip, and nose of Li Guoxing, who was mauled by an Asiatic black bear while protecting his sheep. On 21 December 2008 it was reported that Li had died in July in his home village in Yunnan. Prior to his death, a documentary on the Discovery Channel showed he had stopped taking immuno-suppressant drugs in favor of herbal medication – suggested by his surgeon to be a contributing factor to his death.

A 29-year-old French man underwent surgery in 2007. He had a facial tumor called a neurofibroma caused by a genetic disorder. The tumor was so massive that the man could not eat or speak properly.

In March 2008, the treatment of 30-year-old neurofibromatosis victim Pascal Coler of France ended after he received what his doctors call the world's first successful almost full face transplant.

Turkey's third face transplant was a partial one that was carried out on 17 March 2012 on Hatice Nergis, a twenty-year old woman, at Gazi University's hospital in Ankara by a team led by surgeon Dr. Selahattin Özmen. The patient from Kahramanmaraş had lost, six years before, her upper jaw including mouth, lips, palate, teeth and nasal cavity in a firearm accident, and was unable to eat. She had in the past undergone around 35 reconstructive plastic surgery operations. The donor was a 28-year old woman in Istanbul, who committed suicide.

Full face transplant
On 20 March 2010, a team of 30 Spanish doctors carried out the first full face transplant on a man injured in a shooting accident. It became the first full face transplant in the world.
On 8 July 2010, the French media reported that a full face transplant, including tear ducts and eyelids, was carried out at the Creteil Henri-Mondor hospital.

In March 2011, a surgical team, led by MUDr. Bohdan Pomahač at Brigham and Women's Hospital in Boston, performed a full face transplant on Dallas Wiens who was badly disfigured in a power line accident that left him blind and without lips, nose or eyebrows. The patient's sight couldn't be recovered but he has been able to talk on the phone and smell.
On 19 March 2012, one of the longest and most extensive facial transplants ever (36 hours, from 4 am 19 March to 2–3 PM 20 March; the 23rd ever to occur; from the hairline to the neck, replacing essentially everything but the eyes and the back remnants of the throat) took place on a Richard Lee Norris of Hillsville, Virginia, who had suffered a gunshot wound in 1997 that left him with extensive facial trauma, at the R Adams Cowley Shock Trauma Center at the University of Maryland Medical Center in Baltimore, Maryland. Seven months after the procedure, Norris exhibits remarkable progress. Norris can smile and show facial expressions, and also smell, taste and eat. The motor function on the right side of his face is about 80 percent of normal and motor function on the left side is about 40 percent, according to his doctors.

In Turkey
On 21 January 2012, Turkish surgeon Dr. Ömer Özkan and his team successfully performed a full face transplant at Akdeniz University's hospital in Antalya. The 19-year-old patient, Uğur Acar's face was badly burnt in a house fire when he was a baby. The donor was 39-year-old Ahmet Kaya, who died on 20 January.[24] The Turkish doctors declared that his body had accepted the new tissue.
Almost one month later on 24 February 2012, a surgical team led by Dr. Serdar Nasır conducted the country's second successful full face transplant at Hacettepe University's hospital in Ankara on 25-year-old Cengiz Gül. The patient's face was badly burned in a television tube implosion accident when he was two years old. The donor was 40-year-old N. A. (his family did not allow revealing of his identity), who experienced brain death two days before the surgery following a motorcycle accident occurred on 17 February.

On 16 May 2012, surgeon Dr. Ömer Özkan and his team at the Akdeniz University Hospital performed country's third and their second full face transplant, fourth face transpant in Turkey at all. The face and ears of the 27-year old patient Turan Çolak from Izmir were burnt as he fell into an oven when he was three and half years old. The donor was Tevfik Yılmaz, a 19-year young man from Uşak, who had attempted suicide on 8 May. He was declared brain death in the evening hours of 15 May after having been in intensive care station for seven days. His parents donated all his organs.

In the United Kingdom
In October 2006, surgeon Peter Butler at London's Royal Free Hospital in the UK was given permission by the NHS ethics board to carry out the face transplant. His team will select four adult patients (children cannot be selected due to concerns over consent), with operations being carried out at six-month intervals.

In the United States
In 2004, the Cleveland Clinic in Ohio, United States, became the first institution to approve this surgery and test it on cadavers.
In 2005, the Cleveland Clinic became the first US hospital to approve the procedure. In December 2008, a team at the Cleveland Clinic, led by Dr Maria Siemionow and including a group of supporting doctors and six plastic surgeons (Dr Steven Bernard, Dr Mark Hendrickson, Dr Robert Lohman, Dr Dan Alam and Dr Francis Papay) performed the first face transplant in the US on a woman named Connie Culp. It was the world's first near-total facial transplant and the fourth known facial transplant to have been successfully performed to date. This operation was the first facial transplant known to have included bones, along with muscle, skin, blood vessels, and nerves. The woman received a nose, most of the sinuses around the nose, the upper jaw, and even some teeth from a brain-dead donor. As doctors recovered the donor's facial tissue, they paid special attention to maintaining arteries, veins, and nerves, as well as soft tissue and bony structures. The surgeons then connected facial graft vessels to the patient's blood vessels in order to restore blood circulation in the reconstructed face before connecting arteries, veins and nerves in the 22-hour procedure. She had been disfigured to the point where she could not eat or breathe on her own as a result of a traumatic injury several years ago, which had left her without a nose, right eye and upper jaw. Doctors hoped the operation would allow her to regain her sense of smell and ability to smile, and said she had a "clear understanding" of the risks involved.

The second partial face transplant in the US took place at Brigham and Women's Hospital in Boston on 9 April 2009. During a 17-hour operation, a surgical team led by MUDr. Bohdan Pomahač, replaced the nose, upper lip, cheeks, and roof of the mouth – along with corresponding muscles, bones and nerves – of James Maki, age 59. Mr. Maki's face was severely injured after falling onto the electrified third rail at a Boston subway station in 2005. In May 2009, he made a public media appearance and declared he was happy with the result.[31] This procedure was also shown in the eighth episode of the ABC documentary series Boston Med.

The first full face transplant performed in the US was done on a construction worker named Dallas Wiens in March 2011. He was burned in an electrical accident in 2008. This operation, performed by Dr. Bohdan Pomahač and Dr. Jeffrey Janis, was paid for with the help of the US defense department. They hope to learn from this procedure and use what they learn to help soldiers suffering from facial injuries.[33] One of the top benefits of the surgery was that Dallas has regained his sense of smell.

57-year old Charla Nash, who was mauled by a chimpanzee in 2009, underwent a 20-hour full face transplant in May 2011 at Brigham and Women's Hospital in Boston. Nash's full face transplant was the third surgery of its kind performed in the United States, all at the same hospital.
In March 2012, a face transplant was completed at the University of Maryland Medical Center and R Adams Cowley Shock Trauma Center under the leadership of plastic surgeon Eduardo Rodriguez, DDS, MD and his team (Amir Dorafshar MBChB, Michael Christy MD, Branko Bojovic MD, Daniel Borsuk MD). The recipient was a 37-year old man who had suffered a facial ballistic injury in 1997. This transplant represents the most extensive to date, and included all facial and anterior neck skin, both jaws, and the tongue.