Fifty years of organ transplants: the successes and the failures.

• Author: Kaserman, David L.

ABSTRACT: More than fifty years have now passed since the first successful human organ transplant. During that time, substantial progress has been made in both surgical techniques and immunosuppressive drug therapy. As a result, transplant success rates have improved dramatically, and thousands of recipients of kidneys, hearts, livers, and lungs have been granted both longer and healthier lives. At the same time, however, many more thousands of patients have died while waiting in vain for a cadaveric donor organ to become available due to a severe and persistent shortage of such organs. That shortage, in turn, is directly attributable to the National Organ Transplant Act of 1984, which proscribes payment to potential organ donors, even if that would increase supply. This atavistic policy and the shortage and deaths it has spawned provides a stirring example of the tendency for public policy to lag behind technological advancement, particularly in the medical field. But the tide of medical opinion may be turning on this issue, and some form of donor payments may soon emerge.

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The first successful human organ transplant in the U.S. was performed on December 23, 1954. (1) On that date, a kidney was successfully transplanted, with the organ donated by a living identical twin of the recipient. Since then, organ transplantation has moved from the experimental stage to assume an important role in the treatment of organ failure stemming from a wide variety of underlying causes. Today, kidneys, hearts, livers, lungs, and other organs are routinely transplanted to patients whose lives would otherwise soon be ended. Moreover, unlike some life-extending measures that substantially lower the quality of life, where organ transplants succeed, recipients' health can be restored dramatically.

The extension of transplantation technology to non-renal organs during the 1970s and 1980s greatly increased the potential to save lives through the use of this treatment modality That extension required the utiliration of cadaveric--as opposed to living--donors. And the use of cadaveric organs, in turn, was made feasible by a series of technological advances, primarily in the form of new immunosuppressive drugs. Beginning with the discovery of cyclosporine in the late 1970s, and its subsequent approval in the U.S. in 1983, newer, more effective drugs have been introduced periodically to prevent the principal cause of transplant failure-rejection of the transplanted organ by the recipient's own immune system. (2) As these new drugs have appeared and physicians' experience with their administration has accumulated, organ rejection rates have fallen almost continuously.

As is becoming increasingly commonplace in this age of rapid technological change, however, the amazing potential of organ transplantation to save lives is being severely constrained by the failure of public policy to keep pace with technological advances. Specifically, U.S. (and other countries') cadaveric organ procurement policies have failed to respond effectively to the rapid growth in the demand for transplantable organs that has resulted from the significant strides achieved in immunosuppressive therapy The result has been a chronic and growing shortage of human organs made available for transplantation.

That shortage, in turn, denies this life-saving treatment to thousands of Desperately ill patients, who now occupy ever-increasing organ waiting lists. Today, over 87,000 patients are on these lists awaiting transplantation. And, tragically, at current collection rates, approximately half will die before the needed organs become available. Indeed, in each of the last four years, more than six thousand would-be transplant recipients (more than twice the number lost in the 9/11 attacks) have died while waiting in vain for the needed organs. (3) And this number continues to increase each year that the shortage remains unresolved. In the meantime, thousands of organs that could have provided life-saving transplants go uncollected and are buried along with the potential donors.

Now, as we mark the 50th anniversary of the birth of this important medical technology, it seems appropriate to document both the successes and failures we have experienced to date. It is also a good time to take stock of what we have learned regarding the potential of alternative public policies that have been proposed in recent years to resolve, or at least ameliorate, the organ shortage. Only through an accurate and dispassionate assessment of these alternative policies can we hope to narrow the eve-widening technology/policy gap that is now costing so many lives.

The Successes

The successes achieved in organ transplantation over the past fifty years are nothing short of remarkable. As the ability to suppress the body's immune system has advanced with the discovery of new drugs, rejection rates have fallen dramatically. For example, prior to the introduction of cyclosporine, one-year graft survival rates were approximately 70 percent for kidneys, 58 percent for hearts, and 25 percent for livers. By 2001, these rates had risen to 90, 84, and 80 percent, respectively. (4) Moreover, these increased success rates may understate somewhat the improvements that have been achieved, because organ transplants are now being performed on some patients whose health would have prohibited use of this treatment modality two decades ago.

Along with this decline in rejection rates, the expected life of a transplanted organ has lengthened commensurately. For example, in the early 1990s, the expected life of a cadaveric kidney transplant was on the order of 4-5 years. Today, however, Alan Leichtman, of the University of Michigan, reports that:

In general, two-haplotyped matched living related donor kidney transplants have a 50% chance of achieving 24 years of function, one-haplotyped matched living related donor kidney transplants have a 50% chance of achieving 12 years of function, and cadaver donor kidney transplants have a 50% chance of achieving 9 years of function. (5) This lengthening of graft survival times means that patients' lives are being Greatly extended and the necessity of second (and third) transplants has been reduced accordingly.

These technological advances have caused considerable growth in the demand for organ transplants. In addition, public policy has also played a significant role in increasing transplant demands. It has done so in two fundamental ways. First, the not-so-subtly-named End Stage Renal Disease (ESRD) program was created by the U.S. Congress in 1972. (6) This program provides federal funding for all renal transplants performed on U.S. citizens in this country, regardless of the patient's age or income. Moreover, such funding has also been extended to some non-renal transplants in recent years. As a result, expenditures under this program have grown from $229 million in 1974 to over $15 billion in 2002. (7) Also, private health insurance companies have extended coverage to heart, liver, and other organ transplants as these procedures have moved from the experimental phase to accepted treatment modalities. Such third party payments extend the transplantation option to many patients who would otherwise be unable to afford it. And second, the federal government's ESRD program funds dialysis treatments for all U.S. citizens suffering renal failure. Such treatments, in turn, keep these patients alive much longer than they would otherwise survive and, thereby, further increase the effective demand for kidney transplants.

As a consequence, then, of both technological advances and expanded funding, the demand for organ transplants has grown tremendously. (8) Moreover, while the supply of transplantable organs has failed to keep pace with this increasing demand, it has, nonetheless, grown considerably as well. The result has been significant growth in the number of organ transplants performed. Table 1 documents this growth for the four organs most frequently transplanted over the period for which consistent data are available, 1988-2003. (9)

Several points are worth noting from these figures. First, while the number of transplants has grown over this fifteen year period for each of these organs, the observed rates of growth have varied considerably by organ. For example, while the number of kidney transplants has increased from its 1988 value by 70.4 percent, the number of heart transplants grew by only 22.7 percent. At the same time, the number of liver transplants has grown by 231 percent, and the number of lung transplants has risen over 3,000 percent. (10) Second, while the growth in the number of transplants has been fairly continuous for kidneys, livers, and lungs, the number of heart transplants peaked in 1995 and has actually fallen slightly since then. The reason for this decline is not immediately apparent. Finally, the total number of transplants performed across all four organs has grown 95 percent over this decade and a half. Adjusting for the approximate one-year rejection rates for these organs, these numbers indicate that somewhere around 200,000 patients have received successful, life-extending organ transplants over this period.

Finally, while some modern medical treatments tend to extend the patient's life only at great cost in terms of the quality of life, a successful organ transplant, while not a complete cure, can often restore the patient's health substantially. (11) Indeed, many successful transplant recipients have used the term "rebirth" to describe their experience. Thus, this medical technology, first introduced in the mid-1950s, is responsible for relieving suffering and extending the lives of many critically ill patients. As we shall see, it could have delivered far greater benefits if cadaveric organ procurement policy had been able to keep pace with the growing demand.

The Failures

While the successes achieved through...