The Development of Organ Transplantation

Overview

By the mid-twentieth century surgeons began successfully transplanting human organs in order to save the lives of patients whose organs were failing from disease. These procedures were at first sensational, sparking debate among the medical community and the general public. In order for a transplantation to take place, a donor was required. With many organ transplantations, the donor was deceased at the time of donation. This startling development in medical history was, in fact, less sensational than the product of years of careful research. The field of human organ transplantation required many of the fields of medicine—surgery, histology, and immunology, for example—to unite in its cause. The research and performance of human organ transplants throughout the second half of the century resulted in more Nobel Prize awards than any other medical field in history. Within 50 years, kidney, liver, and heart transplants moved from experimentation to mainstream medical treatment for patients with failing organs and few other options to regain health.

Background

The transplant barrier was broken in 1954, with the first successful human kidney transplant. American surgeon Joseph E. Murray (1919- ) led a team of surgeons performing the transplant procedure at a hospital in Boston, Massachusetts. The patient received a transplanted kidney from his living twin brother, and the kidney functioned normally for eight years. Murray attempted the procedure after years of studying how the body accepts or rejects donor tissue. Murray noticed that skin grafts applied to burn patients as a temporary measure were slowly rejected by the body, while skin grafts among identical twins were successful. By 1962, as the first generation of drugs were available to suppress the body's immune response and therefore counteract the rejection of the new organ, the first successful kidney transplant from a cadaver (deceased) donor was performed, again in Boston. The kidney functioned for 21 months. In 1990 Murray was awarded the Nobel Prize in medicine for his pioneering work in transplantation.

The Development of Organ Transplantation

Overview

Background

Although a kidney from a related donor is less likely to be rejected from the body, cadavers became the most common source for donor kidneys, due to greater availability and eliminating the risk to living donors. By the end of the century kidneys were the most commonly transplanted organ, and kidney transplantation became mainstream treatment for end-stage renal (kidney) disease.

American surgeon Thomas Starzl (1926- ) performed the first human liver transplant at the University of Colorado in 1963. The procedure garnered much initial enthusiasm among the medical community as a possible treatment for end-stage liver disease, at that time almost always fatal, as no supplementary technology was available (such as in kidney dialysis) to help perform the work of the liver. This enthusiasm was diminished when the first seven patients to undergo liver transplant, at three different medical centers, all died within one month of the transplant. Liver transplants were temporarily suspended in order for scientists to explore the complex and serious post-operative complications the liver transplant patients suffered, notably organ rejection, infection, and pulmonary emboli (blood clots or air trapped in the lungs). Starzl's research focused on the body's immune response, which rejected the new liver. Important improvements in surgical technique were also learned from ongoing kidney transplantation. In 1967 Starzl and his team attempted another liver transplant, aided by the introduction of more potent anti-rejection drugs. The liver functioned successfully for 13 months. By the late 1990s approximately one hundred transplantation centers across the United States had performed liver transplants, with Starzl training physicians in many of these centers. The demand for liver transplants grew until, by the end of the century, nearly 30% of patients eligible for liver transplants died while waiting for a donor organ.

Transplantation captured world-wide attention in 1967, when South African surgeon Christiaan Barnard (1922- ) performed the world's first human heart transplant. Barnard and his team of physicians and nurses at Groote Schuur Hospital in Cape Town, South Africa, removed the heart of a 55-year old man and replaced it with the healthy heart of a 25-year old woman who had died earlier of injuries sustained in an automobile accident. The patient survived 18 days after the transplant, dying from pneumonia as a result of an immune system suppressed to prevent rejection of the donor heart. Barnard performed his second heart transplant in 1968. The patient achieved notoriety as a symbol of hope for victims of heart disease and spurred the transplantation process, surviving 563 days after the operation. Also in 1968 American surgeon Norman Schumway performed the first successful heart transplant in the United States. Both surgeons continued to develop and refine surgical techniques for the burgeoning field of heart transplantation. It was not until the early 1980s, however, with the advent of cyclosporin and other next-generation anti-rejection drugs, that the heart transplant procedure became widely accepted. By the 1990s heart transplantation evolved from an experimental operation to an established treatment for advanced heart disease, with over two thousand performed yearly in the United States.

Impact

Transplants are considered when a major organ of the body is failing and does not respond to all other therapies, but otherwise the health of the patient is good. Patients receiving successful transplants are often able to resume their daily lives with no dependence on complicated medical machinery, such as a kidney dialysis machine or a heart pump assistive device. Although transplant recipients must adhere to strict regimens of medications and frequent examinations, increased survival rates at the turn of the century enabled over 75% of successful transplant recipients to return to a daily work schedule and to recreational activities enjoyed prior to becoming ill.

As organ transplant procedures increased and became standard treatment for otherwise fatal illnesses, both the medical community and the public at large considered ethical issues brought forth by organ donation. The National Transplantation Act, passed by the U.S. Congress in 1984, mandated a centralized system for sharing available organs along with a scientific register to collect and report transplant data. The act also made illegal the sale or purchase of organs.

A national system was established to match donors and recipients; it is managed by the United Network for Organ Sharing (UNOS). UNOS members work with all transplant centers in the United States to ensure that the limited supply of organs is distributed fairly to patients in need regardless of age, sex, race, lifestyle, or financial or social status. Through the UNOS Organ Center, organ donors are matched to waiting recipients every day of the year, around the clock. Organ sharing is based upon scientific criteria including the recipient's acuity (urgency state) of the disease process, compatibility of body size and blood chemistries, as well as length of time on the waiting list. At the close of the century, new laws were under consideration designed to remove any geographical bias in organ allocation. The Scientific Registry maintained by UNOS contains data on every solid organ transplant since 1987 and is one of the most comprehensive data analysis systems targeting a single therapy in the world. Patient confidentiality is maintained with a number system, and scientists are able to quickly exchange information vital to the progress of transplantation.

With increases in the number of transplants performed, UNOS and public health organizations attempted to raise public awareness of the importance of organ donation. States included organ donor status on citizens' driver's licenses, and a universal donor card was widely publicized. By the 1990s most states had passed legislation requiring medical personnel to approach all potential donor patients, or if the patient is unable, their families, for a donation decision. The criteria for brain death was clarified in 1981 by a presidential commission on medical ethics to allay public concern regarding time of death and organ recovery. All major religions in the United States voiced opinions encouraging personal choice and organ donation.

In spite of these efforts, the demand for donated organs has far outnumbered the supply. By the turn of the century, over 67,000 Americans were on the UNOS national patient waiting list. At the same time, transplantation procedures were quickly growing. Organs and tissues were needed for additional types of transplants added to the medical arsenal against disease. Lung, pancreas, bone marrow, small intestine, cornea—all were considered an acceptable part of medical treatment. To potentially ease the shortage, some scientists experimented with xenotransplantation, or transplanting an organ of another species into a human. A celebrated xenotransplantation case was that of "Baby Faye," into whom a baboon heart was transplanted in 1984 at the Loma Linda Medical Center in California. Baby Faye's baboon heart functioned for 20 days. Xenotransplantation remains experimental, as do artificial mechanical organs—scientists continue to study both of these measures as potential "bridges" to serve a critically ill patient until a donor organ can be located.

BRENDA WILMOTH LERNER