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History of Organ and Tissue Transplant

Medicine and Law

The dream of curing illness and injury by transplanting organs, bone and other tissue is probably as old as the history of healing with the first recorded attempts to transplant bone dating back to the Middle Ages. Unfortunately the scientific knowledge and surgical techniques that have made modern transplant medicine possible had to wait until the 19th and 20th centuries. Successful transplantation of bone, skin and corneas came first, with advances made between 1900 and 1920. The establishment of the U.S. Navy Tissue Bank in 1949 gave the nation its first bone and tissue processing and storage facility. By 1986 there were more than 300 nonprofit bone banks in operation, although consolidation has since decreased that number by almost half.

Progress in solid organ transplantation began in the 1950s. Dr. Joseph E. Murray (who received the Nobel Prize for Medicine in 1990) achieved the first successful kidney transplant between identical twins in Boston in 1954. In 1967, a young South African heart surgeon named Christian Bernard became an international hero when he performed the first human heart transplant at Groote Schur Hospital in Cape Town.

While most of the technical problems associated with implanting an organ had been overcome early in the century, the long-term outlook for recipients was still far from ideal. The major problem was the tendency of the body’s immune system to become activated against the “foreign” organ and to mount a response designed to kill the invader (rejection). In order to prevent rejection, patients were given strong medications to suppress their entire immune system that in turn left them susceptible to life threatening infections. It was not until 1978, when the immunosuppressive drug Cyclosporin was introduced, that many of the problems of rejection were controlled. Since then, other drugs have been developed which specifically target only those cells involved in the rejection process while leaving the remaining immune system intact. These include drugs such as FK506, Atgam, Orthoclone OKT3 and Prograf. Today, one-year survival rates for most organs are between 70% and 90%.

As transplant medicine accelerated, it produced a wealth of legal and ethical concerns, the most critical of which related to the determination of death. Technology had improved to the point in the 1960s where the body could be maintained with artificial support long after the brain had died. A new definition of death was required; one that included situations where the entire brain and brain stem had irreversibly ceased to function (brain death). This determination is critical to organ donation as it allows recovery before cessation of blood flow to the organs. Prior to brain death, organs could only be recovered after the heart had stopped beating, which limited transplants to kidneys and livers only. Brain death allowed the additional recovery of the heart, pancreas, lungs and intestines. The first standard set of neurologic criteria for determining death were developed at Harvard University in 1968 and 1969. These criteria have since been adopted by all 50 states, as has the Uniform Anatomical Gift Act that addresses the conditions governing donations. The National Transplant Act, passed by Congress in 1984, mandated many of the regulations safeguarding the donation process (outlawing the sale and purchase of human organs and tissue, for example) and set up a national waiting list for patients needing an organ transplant. In 1986 the federal government amended the Social Security Act to require all hospitals receiving Medicare funds to notify the families of potential donors about their option to donate (“Required Request”). After donation rates remained fairly constant the federal government passed additional legislation in 1998 requiring hospitals to notify their local Organ Procurement Agency of all deaths so that trained and experienced staff could screen potential donors and offer the option of organ and tissue donation when appropriate (“Routine Referral”).

In the late 1980s, the Food and Drug Administration announced its intention to regulate tissue banking, beginning this oversight at the end of 1993. Regulation was designed to reduce the possibility of infectious disease transmission by setting standards for donor screening and testing. Additional regulations dealt with record keeping, labeling and tracking. In 1998 legislation required the registration of all tissue processors. Proposed legislation in 1999 included regulation of all human tissue and cellular based products, additional donor screening and reproductive technologies utilizing human sperm and oocytes.

The rapid development of transplant medicine since the 1970s, combined with factors including general population, growth and expansion of the elderly population has caused increasing demand for donated tissues and organs. Today it is estimated that approximately 600,000 Americans benefit from some from of transplant each year. While this is impressive, patients still die daily awaiting a vital organ and many remain debilitated and in pain for lack of a tissue transplant.

Historical Highlights

1668First successful bone graft (bone from a dog’s skull used to repair defect in human cranium) documented by Job van Meeneren (Dutch).
1674Description of bone structure by Antoni van Leeuwenhock (Dutch).
1822Fresh autograft ( transplantation of tissue from one location on an individual’s body to another location) of skin, by Berger.
1867L. Ollier (France) publishes treatise showing that bone autografts are viable: Traite experimental et clinique de la regeneration des os.
1868Fresh allograft (transplant from one individual to another) of skin by Swiss surgeon Jacques Louis Reverdin.
1880First clinical bone autograft, by William Macewen (Sweden).
1906First corneal transplant, by Dr. Edward Zirm.
1908Successful cadaveric knee joint transplant, by Dr. Eric Lexer.
1911First use of homologous vein tissue in arterial reconstruction, by Dr. Yamanouchi.
1915F.H. Albee publishes influential text on bone graft surgery.
1949U.S. Navy establishes first U.S. tissue bank at Bethesda, Maryland.
1954First kidney transplant (brother to brother) performed by Dr. Joseph E. Murray, Peter Brent Brigham Hospital, Boston, Massachusetts.
1955First fresh heart allograft put into descending aorta, By Dr. Gordon Murray.
1956Frozen venous allograft for femoral bypass, by Drs. Shaw and Weelock.
1962First fresh heart valve transplants in cardiac position, by Sir Brian Barrett-Boyes (New Zealand) and Dr. Donald Ross (Great Britain).
1963First liver transplant, by Dr. Thomas Starzl, University of Colorado, Denver.
1964First lung transplant, by Dr. James Hardy, University of Mississippi, Jackson.
1967First heart transplant, by Dr. Christian Barnard, Groote Schur Hospital, Cape town, South Africa.
1968National Conference of Commissioners on Uniform State Laws draws up first legislative proposal addressing organ donation, the Uniform Anatomical Gift Act (UAGA).
1968First definition of brain death based on neurologic criteria, The Harvard Criteria For The Determination Of Brain Death (amended, 1969).
1969First pancreas transplant, by Dr. Lillche, University of Minnesota, Minneapolis.
1970sFirst use of cryopreserved (frozen) heart valves, by Dr. Mark O’Brien (Australia) and Dr. William Angell (Stanford Medical Center, Palo Alto, California).
1972Introduction of cryopreserved human skin allografts.
1973Use of cryopreserved venous allograft, by Drs. Dent and Weber.
1976American Association of Tissue Banks (AATB) established.
1978Introduction of Cyclosporin as a major immunosuppressant.
1978Kidney transplants included under Medicare coverage (Social Security Act Amendment, P.L. 92-603).
1979National Conference of Commissioners on Uniform State Law recommends Uniform Determination of Death Act for adoption by all 50 states.
1980President’s Commission for Study of Ethical Problems in Medicine and Biomedical Research establishes neurologic criteria for determination of death, expanding on the Harvard Criteria.
1981First heart/lung transplant, by Dr. Norman Shumway, Stanford Medical Center, Palo Alto, California.
1984National Transplant Act (P.O. 98.507) establishes National Task Force on Organ Transplantation, legislates federally funded centralized waiting list for organ recipients, outlaws buying and selling of human organs, mandates establishment of scientific registries to monitor transplant centers, Organ Procurement Organizations and hospitals.
1985Oregon, California and New York become first states Required Consent Laws mandating that hospitals ensure that families of potential donors are offered the opportunity to donate.
1986Consolidated Omnibus Budget Reconciliation Act (P.L. 99-509) amends Social Security Act to require all hospitals to adopt policies and procedures for identification of potential donors and notification of families of their option to donate. The Routine Notification requirement supersedes state laws and directly ties Medicare funding to hospital compliance.
1988Joint Commission on Accreditation of Health Care Organizations sets donor identification and notification standards.
1989200,000 tissue transplants performed in the U.S.
1993Food and Drug Administration initiates regulation of all U.S. tissue banks.
1996500,000 tissue transplants performed in the U.S.
1996National performance standards for Organ Procurement Organizations implemented by the Health Care Finance Administration (HCFA).
1997Food and Drug Administration requires registration of all tissue recovery and processing facilities.
1998Federal legislation “Routine Notification” requires all hospitals to notify their local Organ Procurement Organizations of each death and links compliance to Medicare reimbursement.
1999Food and Drug Administration proposed further regulations extending oversight to all products derived from human tissue and cells including reproductive technology.
2000Almost 112,000 people waiting for an organ transplant and one million waiting for a tissue transplant.
2005First successful partial face transplant in France.
2006First jaw transplant to combine donor jaw with bone marrow from the patient, by Eric M. Genden at Mount Sinai Hospital, New York.
2008First successful complete full double arm transplant by Edgar Biemer, Christoph Höhnke and Manfred Stangl at the Technical University of Munich, Germany.
2008First baby born from transplanted ovary.
2008First transplant of a human windpipe using a patient’s own stem cells, by Paolo Macchiarini in Barcelona, Spain.
2008First successful transplantation of near total area (80%) of face, (including palate, nose, cheeks, and eyelid by Maria Siemionow in Cleveland, Ohio.
2010First full facial transplant, by Dr Joan Pere Barret and team at the Hospital Universitari Vall d'Hebron in Barcelona, Spain.
2011First double leg transplant, by Dr. Cavadas and team at Valencia's Hospital La Fe, Spain.