Having failed to sufficiently scare the general population with dire predictions of death and devastation from such complex diseases as cancer and AIDS, the biomedical research / health care complex has mounted another assault on our collective fears and anxieties. This time the "threat" is a theoretical shortage of organs for use in clinical transplantation. The self-proclaimed solution to this problem is the use of various body parts, tissues, organs and cells of healthy animals for implantation into unhealthy human recipients. This is the basic concept and justification of xenotransplantation. But is it necessary? Are there more humane and medically appropriate solutions?

Humans face very real medical problems, the solutions for some of which are often ignored or de-emphasized. Government officials, high-profile surgeons and researchers, pharmaceutical and biotechnology companies and medical center administrators often promote such high-technology, high-risk, high-cost and very high-profit procedures as xenotransplantation. Reputations, careers and institutional incomes depend more on such "cutting edge" medical science, rather than simpler, low-technology, more intuitively obvious alternatives. But the alternatives still exist.

Although there are only a handful of clinical research centers currently involved in planning and/or conducting xenotransplantation experiments with human patients, investigators have found a gold mine of research possibilities, involving a wide variety of species, essentially every internal organ and body part (except the brain) and tissue (including the brain). The number of possible combination of transplants, anti-rejection drugs and treatment protocols is endless; providing decades of justification for scores of animal-based research laboratories. But is any of this research activity necessary if alternatives are already available?

The current haste to approve xenotransplantation clinical procedures appears to have more to do with politics, pressure tactics of transplant surgeons and AIDS activists, along with the efforts of the biotechnology/medical/pharmaceutical companies to claim their respective share of the 20- to 100-billion-dollar market estimated to exist if animal organs can be successfully transplanted into human patients. A hidden agenda may be the need to someday explain to taxpayers and patients why billions of dollars of research funds have been spent on xeno-related animal experimentation.

All of this activity is conveniently masked by medical assertions that there are not enough human organs and tissues to meet current and projected clinical transplantation needs. Is this shortage real? Have all available alternative organ procurement strategies been tried and failed? No! There is no shortage of organs and tissues suitable for use in patients. As a society, we routinely burn or bury a sufficient number of viable organs and tissues to meet clinical demands. What is needed are alternative means to increase the number of donors and to replace the presently inefficient and flawed system for acquiring organs and selecting recipients. Based on the experience of other countries and simple common sense, there are numerous non-xenotransplant options which federal and state governments could take immediately to increase the number of organ donors.

Proponents of xenotransplantation would have the general public believe that there is a severe and growing shortage of human organs for clinical use. Available statistics, however, suggest a different situation. Although routinely citing the total number of people on the U.S. organ waiting list (more than 50,000) and the number that died waiting (4,022 in 1996), the actual picture is more complex. From 2 to 5 percent of the waiting list numbers are multiple listings for the same individuals, with 69 percent (down from 87 percent in 1988) of those remaining needing new kidneys. Any significant increase in numbers of organ donors should easily accommodate all of the non-kidney transplant patients and eventually everyone.

The real problem is not all of the people on the waiting list, although its sheer size is often used to create a sense of urgency among supporters of xenotransplantation. As a nation, the primary concern is for the approximately 4,000 individuals who died without receiving a suitable organ. This is a more manageable number. In fact, relatively minor increases in donations and better recovery of organs from existing donors could easily solve this aspect of the problem.

Organ Retrieval

How well do Organ Procurement Organizations (OPOs) in the United States conduct their responsibilities? Again, statistics suggest a less than stellar performance. For example, in 1996, OPOs secured kidneys from 93 percent of donors; livers from 82 percent; and significantly less for other needed organs. OPOs are supposed to have working relationships with at least 75 percent of the hospitals in their geographic areas. A recent survey found that only 21 percent of OPOs have more than half of the hospitals reporting all deaths.

Many donors referred to OPOs do not meet their restrictive acceptance criteria. In 1995 two-thirds of potential donors were rejected either because the families refused to cooperate or the organs were judged unsuitable. In fact, donor acceptability criteria vary greatly between different OPOs. A 1997 U.S. General Accounting Office (GAO) study found that based on criteria of number of organ donors and organs actually transplanted, nearly 20 OPOs were not meeting set performance standards. Further, the GAO found that "most OPOs would have been subject to termination under a standard based on the number of deaths and adjusted deaths." A 1997 study by the Coalition on Donation found that 84 percent of OPOs would only act after obtaining family approval (regardless of the donor's wishes); up to 60 percent rarely checked for advance directives by potential donors; and only 26 percent would use a national donor registry — if it were available.

The same Coalition report suggested several legal and procedural changes needed to increase the performance of OPOs. These recommendations included:

1. changing laws which require consent of next of kin, even if the patient has indicated a desire to donate organs;

2. increasing the penalty to OPOs not complying with required federal organ donor laws; and

3. developing educational programs to promote coordination between lawyers, physicians and hospitals to encourage patients to make written directives regarding organ donation.

Finally, the Coalition suggested that it was time to institute a policy of simply informing families of the donor's choices, rather than asking for consent or confirmation.

The GAO analysis also computed the number of actual potential donors available. In 1994 there were approximately 16,000 organs transplanted from 5,100 donors; with 37,600 people on the waiting list. According to the GAO, "adjusting for cause of death and limiting consideration to deaths of those under age 75, we found that in 1994 about 147,000 or 6 percent of the 2.3 million U.S. deaths involved these causes of death or were from this age group." This means that there are more than enough donors to meet 1996, 1997 and 1998 clinical organ needs, and there are a number of other actions that could be taken to increase the number of organ donors as well. This year the Department of Health and Human Services (HHS) adopted a new rule that hospitals associated with Medicare are now required to report all deaths to one of the 63 national OPOs. Estimates suggest this may increase organ donations by as much as 20 percent, enough to meet the needs for several types of organs. HHS and the International Cemetery and Funeral Association recently developed a working group to increase public and professional awareness of the need for organ and tissue donations. Currently, although 85 percent of the public support organ donation, only 20 percent consent to becoming organ donors.

A 1996 survey of all French transplant teams suggested that much of their organ shortage was the result of faulty bookkeeping. Nearly half of the patients on waiting lists were removed because they were either already recipients, had died, could not be found, or had changed their minds about the operations. Spain developed a decentralized network of specifically trained transplant coordinators whose primary responsibility was organ procurement. This was designed to remove problems associated with reluctant or incompetent physicians and hospital staff. By 1995 organ retrieval rates in Spain were up 83 percent. In 1996, the British Transplantation Society conducted a comprehensive study of the organ donation issue. They found that both medical and financial practices still worked against efficient organ procurement. Further, simple educational policy changes in more than 30 European organ donation programs were sufficient to significantly increase the number of donors.

Although academic, commercial, and medical research centers are all spending billions of dollars in an attempt to successfully place animal organs in human patients, there is not an equally vigorous effort to improve the success rates for "marginal" or "immunologically difficult" human donor organs. How have other countries addressed and, in some cases, apparently solved their organ donation problems? Usually by simple, low-technology changes in public attitudes and policies.

Liberalization of organ donor acceptance criteria is a first step. American OPOs use highly restrictive standards. Individuals over the age of 65 account for 73 percent of U.S. deaths, but only 5 percent of organ donors. There is a need to greatly expand the use of organs from non-heart-beating donors, non-related living donors, and place less emphasis on the specific causes of death. Many current limitations based on age and health contribute more to the problem than the solution. There needs to be greater use of partial organ donations, especially for those patients needing a new liver.

Several economists and lawyers have proposed providing financial incentives or rewards to promote organ donation. In such a system the donor's beneficiaries would receive some type of benefit (e.g., monetary or hospital care credits) as part of the donor's estate. Such payments would be made if the organs were retrieved and used. Such a system would eliminate "the exclusive reliance on altruism" as well as adhering "to principles of autonomy and individual choice of donors and their families," says J. Blumstein of the School of Law Vanderbilt University. Current estimates suggest that such financial incentives might produce up to 80,000 organ donations each year — enough to meet current clinical demands.

Evidence from Egypt and India suggests such inducement works, involving a contract for sale of organs upon the donor's death. This is not to be confused with the sale of organs from living donors, which probably should remain unsupported. In 1996, Sweden instituted a mandated choice law, in which all adults were required to choose between donating or not donating their organs. There was an immediate increase of 600,000 potential donors. A similar 1990 law in Denmark increased their donor registry by 150,000.

Surveys of U.S. public opinion indicated that 90 percent would support such a mandated choice law and 93 percent would honor the wishes of the family member making the choice if the wishes were known. As with other required choice options, a national donor registry would be necessary and have easy 24-hour access to transplant coordinators.

Perhaps the most dramatic increases in organ donation have come in those European countries that passed presumed consent laws. Put simply, unless individuals specifically "opt-out" of the system, their organs are presumed to be available for clinical use. Since its passage in 1976, France's presumed consent (PC) law has produced increases in organ donation approaching 5,000 percent. Their primary remaining problems are with medical staff, physicians, nurses, transplant coordinators, and administrators — not with the donors.

Austria passed its PC law in 1982. By the end of 1990, the number of patients receiving kidneys was nearly the same as the number on the waiting list. Organ donations in general were up more than 400 percent. Belgium passed its version of PC in 1986, and organ donation climbed by 183 percent, with multi-organ retrieval significantly increased to 119 percent for kidneys. European transplant experts note that the experience of Belgium and Austria clearly show that "there are enough organ donors for all patients on the waiting lists, at least for kidneys," and that the "problem of chronic organ shortages can adequately be solved in the setting of opting-out legislation."

The American Medical Association (AMA) Council on Ethical and Judicial Affairs examined both mandated choice and presumed consent. They strongly supported the former and only weakly endorsed the latter. For both options there apparently is support from the majority of the American people.

Interestingly, the AMA acknowledged that presumed consent already exists in some states, which permits coroners or medical examiners to remove corneas, pituitary glands, and other tissues from cadavers where there is no specific knowledge of any objections from the donors or their families. A national law would only represent an extension of such policies.

It has also been suggested that a documented willingness to donate organs should be required before anyone is allowed to receive organ or tissue transplants. Because kidney patients make up more than two-thirds of the people on the organ waiting list, they represent a special case. There is a need to increase both living and cadaveric kidney donations. In Norway, living donors comprise 40 percent of the donors and have done so since 1969. Their general attitude is that people can survive with only one kidney. In the United States, such donors make up only 20 percent of the group donating kidneys.

Greater use of cadaveric kidneys, which survive in recipients almost as long as those from living donors, would produce an estimated two- to five-fold increase in available organs and a concomitant decrease in the number of individuals on the waiting list. For the future, researchers are working on ways to transplant half a kidney, thus doubling the number of possible recipients and using developing, early stage organs that are less likely to be rejected.

Reducing Number of Recipients

Proponents of xenotransplantation assume a long-term trend of increasing numbers of patients requiring organ or tissue transplants. This need not be the case. Formal triage criteria are needed for all types of transplant operations, allocating current limited organ resources to those most likely to survive the operations. As John Fung, University of Pittsburgh transplant surgeon noted, "We all agree that those with no chance of survival should not be transplanted." The Secretary of HHS, Donna Shalala concurred "that allocation policies should not require transplantation in futile cases and should not waste organs."

Improved diagnostic and surgical procedures may eliminate the need for many organ transplants. A simple surgical technique, ventricular remodeling, has removed a significant number of patients from heart transplant waiting lists. Further, physicians at Columbia Presbyterian Medical Center recently used positron emission tomography (PET) machines to determine that up to 40 percent of the patients destined for heart transplants actually only needed bypass surgery.

Perhaps the simplest approach to significantly reducing the demand for organ transplantation would be the sustained, committed, long-term emphasis on disease and injury prevention. If seriously enacted by health-care industries, government agencies, and individuals, such a focus would eliminate the need for all but a small fraction of current transplantation procedures. It would also provide additional benefits in all areas of medicine and public health.

For those who must have high-tech solutions to the organ "shortage," artificial bio-engineered organs may be an acceptable alternative to xenotransplantation. Such hybrids of cells and synthetic frameworks are available now for skin and livers. The latter can be used to keep patients alive either until a human organ is available for transplantation or to support the patient's bodily functions until the original damaged liver can repair itself. Artificial hearts are available to act as bridges to organ replacement, with entirely man-made, permanent organs a realistic future possibility.

Efforts were recently announced for a 5-billion-dollar, ten-year project to produce human hearts from human tissues. Another future application of current biotechnology is the creation of organs and tissues without any donors. Efforts are underway to use human embryonic stem cells to produce special cell and tissue types (e.g., nerves, heart muscle cells). Eventually this technology may produce entire replacement organs, all cloned from the patient's own body. This scenario solves all functional and rejection problems.

In Conclusion

All available evidence strongly suggests that xenotransplantation of organs and tissues represents a major threat to future human health and little or no proven benefit to individual human patients. The basic concept deliberately circumvents all of the natural barriers designed to protect our bodies from harm. There is no convincing evidence that the United States government and medical communities have consistently and aggressively worked to increase the supply of human organs available for transplantation. Further, there is no unquestionable scientific or medical evidence that xenotransplantation clinical experiments will work as promised or should be conducted on human patients who need realistic and reliable treatment options.

Something as dangerous as xenotransplantation should not be rushed into practice before all alternatives have been tried and exhausted; nor should it be market-driven or accelerated by the personal and institutional agendas of surgeons, researchers, and pharmaceutical companies. As this paper has documented, U.S. efforts to secure enough transplantable organs to meet clinical needs remains in their infancy, with a well-known history of failure.