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Presidential Address to The Transplantation Society, 2004: Accomplishments, Ethics, and Scientific Perspectives

Sutherland, David E. R.

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Department of Surgery, University of Minnesota, Minneapolis, MN.

Address correspondence to: David E.R. Sutherland, M.D., Ph.D., Department of Surgery, University of Minnesota, Mayo Mail Code 280, 420 Delaware St. SE, Minneapolis, MN 55455.

E-mail: dsuther@umn.edu.

Thank you, Dr. Groth, for the kind introduction. Our long-standing friendship made it special for me to succeed you as president of this great society.

The Transplantation Society (TTS) was the first organization devoted to the specialty of organ replacement therapy. I gave a brief history of TTS in my welcome address to open the XX International Congress held in Vienna in September 2004 (1). TTS was an international society from the beginning: being so fostered an intellectual exchange on a large scale, facilitating scientific progress and clinical application. For me, personally, 32 years of membership has broadened my cultural horizons and brought friends in every port. It is a privilege to join the list of my distinguished predecessors and to stand as president before you, all of us partners in and contributors to the advancements in the field of transplantation. In my presidential address, I will give you a personal view of the past, present, and future of TTS, including attention to the ethical issues in transplantation that TTS has formally addressed.

TTS was founded in 1966 with the purpose of holding scientific meetings encompassing the entire field. The first International Congress of TTS was held in 1967, and international congresses have been held every two years since the second in 1968. In the decades since its founding, national and regional transplantation societies have been organized, as well as specialty societies devoted to individual organs (such as liver, heart, pancreas, and intestine), complications (such as infections), activities (such as procurement), or challenges (such as xenotransplantation). The opportunity for scientific exchange has become almost overwhelming. The role of TTS has correspondingly expanded progressively, not only to address the ethical issues that are universal to the clinical application of transplantation, but also to provide cohesiveness to a field that touches every branch of medicine.

In addition, there is a business component to TTS, and many changes have occurred in our operations during the last several two-year cycles of councils and officers. The 1994–96 Council (with John S. Najarian as president) redefined the original boundaries of the two hemispheres (East and West), in order to facilitate equitable regional representation in TTS governance (2); Najarian reviewed the historical aspects of this division in his presidential address (3). The 1996–98 Council (with Pekka Häyry as president) established a business office in Montreal (4), greatly facilitating governance and record-keeping by subsequent councils. Furthermore, the 1996–98 Council recognized the desirability of having TTS as an umbrella for specialty transplant societies. Thus, the 1998–00 Council (with Oscar Salvatierra as president) incorporated into TTS the International Xenotransplant Association, which had been founded at the time of the VII International Congress of TTS in Montreal in 1998 (5). The 2000–02 Council (with Carl Groth as president) incorporated several more specialty societies as sections.

The 2000–02 Council also initiated a strategic plan (6 goals, 12 strategies, 47 projects) designed by our Eastern Hemisphere treasurer, Jeremy Chapman, including a partnership with industry that was essential to establish a stable financial base for TTS (6). Groth, noting the uneven application of transplantation throughout the world (7), also formulated the concept of a Global Alliance in Transplantation (GAT) with these goals: establishment of a world registry for all organ transplants, including a database on all living donors; enhancement of the education of transplant personnel through fellowships and establishment of liaisons of sister institutions between developed and developing countries; and development of standards and guidelines for transplantation that would be applicable and adopted globally. More details about GAT are described in the article by Groth and Chapman in this issue of Transplantation (8).

One of the strategic plan’s goals endorsed by the 2000–02 Council was to hire a full-time executive director for TTS; during the next council cycle (2002–04), Philip Dombrowski was appointed, assuming that position in October 2003.

And the 2002–04 Council endorsed the most extensive revision ever undertaken of TTS bylaws (6). The division of TTS into two hemispheres was abolished. Instead, six regions (I: U.S.A. and Canada; II: Europe; III: Latin America; IV: Asia; V: Middle East and Africa; and VI: Oceania) were created (Fig. 1), each of which is guaranteed at least one council representative.

FIGURE 1.

FIGURE 1.

Even our logo has been revised into two versions, depending on the reason and format for display (Fig. 2). The basic symbol—two clasped hands encircled by The Transplantation Society’s name above in English and below in French (Société De Transplantation), reflecting the founding and first meeting sites (New York and Paris)—has been retained. But our acronym (TTS) has been added in bold to the side of one of the logos. Our singularity (unity) is emphasized by the word “The.” We need no other adjective. We are THE Transplantation Society, the first and the only one that encompasses every country and every aspect of transplantation.

FIGURE 2.

FIGURE 2.

When founded, TTS had as its main purpose the organization of the best possible scientific congresses—covering every relevant topic in research and clinical application, with a combination of didactic state-of-the-art lectures and competitive peer-reviewed abstracts for presentation. Collegiality and a multicultural flavor were maintained by altering the site of each congress. The 20 congresses from 1967 through 2004 have been held in 16 cities and 12 countries, in some of the most fascinating and cosmopolitan sites in the world (1).

Ethical issues were topics of debates at each congress and of discussion for each council. Since 1985, various councils have published statements about, or defined the position of TTS on, selected issues. In particular, TTS condemned (1) vending (as opposed to living donation) of organs and (2) the use of executed criminals as a source of organs from deceased individuals (9–15). Although TTS is open to allowing debate at all meetings, individual members must not engage in either of the above practices and are required to sign a declaration to that effect on the membership application. Arguments for allowing (16) or not allowing (17) vending have been made quite strongly by various authors. Personally, I do not see how even a government-regulated or government-brokered system could ever coexist with donation—it will have to be one or the other; otherwise, some people who might have donated will instead sell their organs. In any event, as a member, I am bound to uphold the position of TTS, a position I personally agree with while recognizing the validity of debate. An agenda item for the next council is to reexamine the vending issue within the context of our multicultural constituency and to then restate the position of TTS, an effort that will be coordinated by our ethics committee.

Another goal of TTS is to continuously educate personnel engaged in transplantation, above and beyond what can be accomplished by the congresses. Developed programs that meet that standard of excellence should help deficient or fledgling programs that are just beginning to do so, through mentoring and exchanging personnel—a process that TTS should formally foster.

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Accomplishments of 2002–04 Council

The accomplishments of TTS through the efforts of the 2002–04 Council are many. First, the strategic plan initiated by the previous council has resulted in formal agreements to receive financial support for TTS infrastructure and administration. Currently, our specific partners are the pharmaceutical companies that manufacture and sell the immunosuppressive drugs that are necessary to prevent rejection of organ allografts.

Second, the number of specialty transplant societies affiliated as sections of TTS has expanded to six: the Cell Transplantation Society, the International Society for Organ Distribution and Procurement, the International Xenotransplant Association, the International Pancreas and Islet Transplantation Association, the Intestinal Transplantation Association, and the Transplant Infectious Disease Society. Negotiations are in progress with other transplant specialty societies to become sections.

Third, the 2002–04 Council redefined the journal publication policy for the XX International Congress of TTS. Transplantation Proceedings published submitted papers presented at the first 18 congresses. For the XIX Congress, the 2000–02 Council invited only the authors of the 200 abstracts that received the highest grades to submit papers to Transplantation for peer review; those papers that were accepted were published in a single volume representing the cream of the crop (18). The 2002–04 Council responded to a grassroots initiative by TTS members who wanted all congress papers to have the opportunity to be submitted for publication. As a result, the authors of the top-ranked 200 abstracts are now invited to submit a paper to Transplantation for peer review; the others, to Transplantation Proceedings. Thus, our historical relationship with Transplantation Proceedings is preserved, while we continue the distinctive arrangement with Transplantation, the official journal of TTS.

Fourth, as mentioned, TTS hired a full-time executive director. This addition has greatly improved the administration of TTS and increased the efficiency by which the elected officers of TTS carry out their duties.

Fifth, the major revision of the bylaws that was endorsed by the 2002–04 Council has now been ratified by the membership. Beginning with the 2006 elections, the council will have a president, president-elect, and immediate past president, thereby providing executive continuity; one vice-president; and one secretary (rather than the two—one East, one West—in the past). But the council will retain two treasurers (now called senior and junior, rather than East and West), again to provide continuity in the management of finances. The most important change, again, was the division of the global membership into six regions (Fig. 1), each of which is guaranteed at least one council member. Overrepresentation on the council of any region, according to the proportion of members, will thus be prevented (6).

Sixth, the 2002–04 Council began to implement GAT, as mentioned above and detailed elsewhere (8).

Finally, the 2002–04 Council reaffirmed the ethical positions of TTS opposing (1) commerce in the context of individuals selling their own organs or brokering the vending of others’ organs and (2) the use of executed prisoners as sources of organs for transplantation. Previous councils had expressed concerns about the uncertainty of obtaining uncoerced consent from condemned prisoners and about the possibility of organ procurement being an incentive for a capital crime conviction.

With regard to the six regions, each includes more than one country. Some of the regions have considerable variability in the application of transplantation and in the distribution of TTS members. For example, Region II (Europe) includes a large country (Russia) that has only one member; most of the region’s members are concentrated in western Europe. However, in Region IV (Asia), more than half the members are from one country (Japan). Other regions are fairly uniform, e.g., Region I (U.S.A. and Canada) and Region VI (Oceania, largely Australia and New Zealand).

The available information on the current annual number of organ transplants per million population (∼9 worldwide) shows marked variation by regions (19, 20), ranging from 79 in Region I (U.S.A. and Canada) to <1 in Region V (Middle East and Africa); the number is 4 per million in Region IV (Asia), 6 in Region III (Latin America), 19 in Region II (Europe), and 25 in Region VI (Oceania). The number of TTS members per 100 organ transplants (5.1 worldwide) varies less by region, ranging from 2.3 in Region III (Latin America) to 12.8 in Region VI (Oceania). The number is 4.2 per 100 transplants in Region IV (Asia), 5.2 in Region II (Europe), 5.6 in Region 1 (U.S.A. and Canada), and 5.7 in Region V (Middle East and Africa). One way to increase membership in TTS is to increase the number of transplants, especially in regions where the number is relatively low, because then the membership will follow.

The differences in transplant activity and membership can vary considerably within regions. For example, in Region IV (Asia), Japan’s population is one-tenth that of China, yet Japan does one-sixth as many transplants (8.4 per million population vs. China’s 4.8), China largely with deceased donors and Japan largely with living donors. Yet TTS membership in Japan (140 per 100 transplants) is vastly greater than in China (<1 per 100 transplants), reflecting the economic and social differences between the countries as well as the limits on membership from China because it uses executed prisoners as its main source of organs, making most of its transplant clinicians ineligible.

One objective of GAT is to help expand clinical organ replacement in the regions and countries where application has been limited, recognizing the context of any given area’s general health care needs and economics. We also need better data on application and outcomes from the very regions that most need assistance, hence the objective of a world registry (8).

GAT will effectively link TTS with the World Health Organization (WHO). During the 2002–04 biennium, several officers of TTS met with representatives of WHO. TTS is also inviting the regional transplant societies (American, European, Asian, Latin American, Middle Eastern, and Oceanian) to join this alliance with WHO. The pharmaceutical industries are also important in this endeavor. TTS is the founder and leader of GAT, but GAT will function not just through TTS councils, but also through a GAT board. The GAT board will consist of appointees from TTS and the regional transplant societies; other national and international organizations (such as the International Society of Nephrology); foundations such as the National Kidney Foundation; and charities that focus on end-stage diseases of various organs. Because of legal implications, WHO and our industrial partners will be given observer status on the board, but their participation will be no less important in the implementation of the GAT objectives.

Thus, GAT strategies and projects will be overseen by the GAT board and TTS councils. Projects will be implemented by a management staff. One of the first to be implemented will be the world registry, thanks to the expertise of TTS members who are already involved in regional and international registries. A challenge will be to collect living donor data that will include adverse events. Such data will be crucial to implementing standards for the care not only of recipients but also of living donors. The GAT board will also seek funding mechanisms for fellowships, which will be crucial for the educational relationships between sister institutions of developed and developing countries and for the application of minimum standards of care.

Developing a consensus on standards of care of living kidney donors was addressed by the 2002–04 Council through an international forum (organized by our ethics committee) that was held in Amsterdam in April 2004. More than 100 representatives from more than 40 countries, including nephrologists and surgeons from developing countries around the world, participated. We were able to agree on good standards of care applicable in every participating country. Recommendations were adopted on predonation evaluation; on information mandatory to disclose to prospective donors, including alternatives for the recipient; on the need to provide a donor advocate to ensure an understanding of the voluntary nature of the act and the option to withdraw; and on postdonation care and follow-up. The consensus statement from the Amsterdam Forum was published in Transplantation just before the XX International Congress (21). The scientific information that was critical to the development of the statement will be published in a forthcoming issue of Transplantation (22).

The WHO Assembly met soon after the Amsterdam Forum. WHO invited TTS to provide input for revising resolutions on human organ and tissue transplantation (23). Carl Groth and Jeremy Chapman from the 2002–04 Council, along with Francis Delmonico from our ethics committee, met with WHO representatives, including at a workshop preceding the WHO Assembly by several months. This interaction resulted in resolutions that were much more progressive than those previously published by WHO (24). The new resolutions (23), addressing both allogeneic and xenogeneic transplantation, were published in the same issue of Transplantation as the Amsterdam consensus statement (21). Concerned by the shortage of human donor organs for transplantation, WHO urged member states to (1) implement oversight and promote appropriate practices to ensure the maximal and ethical use of living and deceased allogeneic donors and (2) allow xenogeneic transplantation only when member states have control mechanisms in place to prevent infections (23). Again, the complete resolutions should be read by everyone with an interest in the application and ethics of transplantation.

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Statements on Ethical Issues

As already indicated, ethical issues in transplantation are extremely important for TTS to address. TTS has published six statements since 1985, the last in 1999, all of which have been reaffirmed by the 2000–02 and 2002–04 councils (9–15). Of the six statements, three (1985, 1994, 1995) focused on the commercialization (vending as opposed to donation) of organs from living individuals, condemning commercialization and forbidding members to be involved (9, 12, 15). One (1996) focused on the taking of organs from executed prisoners, again condemning the practice and forbidding members to be involved (13). Two (11, 13) addressed both issues. Arguments against the use of organs from executed prisoners include the lack of transparency in the countries (mainly China) where this occurs, the concern over what are legally designated as capital crimes, the incentives that the organ shortage gives to liberalizing the definition of capital crimes, and repugnancy to capital punishment altogether. All six statements stand as TTS council actions and are thus official positions, with or without the affirmations of sequential councils.

The first statement was published in Lancet in 1985 (9) and in Transplantation (10) in 1986, when Peter Morris was president and Nicholas Tilney was ethics committee chair. It contained six guidelines on deceased donor organ distribution, all meant to ensure objective allocation without political consideration and without favoritism to special groups; seven guidelines on altruistic donation of kidneys by unrelated donors, with criteria similar to that for related donors, but with solicitation for profit unacceptable and payment to the donor by the recipient not allowed (although reimbursement for lost earnings is acceptable); and one resolution that no transplant surgeon or team shall be involved in buying or selling organs or in activity aimed at commercial gain, with any violation a cause for expulsion from TTS. The Lancet article noted legislation making commerce in organ acquisition or transfer illegal in Canada (1972), Europe (1979), and the USA (1984). Since the 1985 TTS statement, most countries with substantial transplant activity have made vending illegal, a few have not addressed the issue, and only one (Iran) has legalized the practice.

The 1990–92 Council (with Thomas Starzl as president and Robert Sells as ethics committee chair) was the first to publish (1993) an objection to the use of organs from executed prisoners (11). The reasons stated were that it dignifies legalized killing, is used to justify the death penalty, symbolically provides a negative aspect to the positive imagery of transplantation, and violates autonomy, with informed consent impossible. The 1993 statement also reaffirmed the 1985 resolution objecting to paying individuals for their organs; documented vending activity; and listed the arguments for vending along with associated problems, including the threat to altruistic donation. (The 1985 resolution had recognized the ethical and cultural differences between societies and had proposed an education strategy of fellowships for third-world professionals; such fellowships, it was hoped, might secondarily lead to cultural and political changes, ultimately increasing donation in areas where such altruism has been nearly nonexistent.)

The 1992–94 Council (with Roy Calne as president and Ross Sheil as ethics committee chair) published a reaffirmation of all six of the 1985 Lancet guidelines on deceased donor organ allocation (12). The one change was to eliminate the wording that organs shared between networks should go only to nonprofit centers. The guidelines on living kidney donors were reaffirmed without modification: no payment to the donor can be allowed, except for reimbursement of expenses (9, 12).

The 1994–96 Council (with Najarian as president and Sheil continuing as ethics committee chair) published a policy statement in 1995 (13). It recommended that all countries (1) define brain death and enshrine that definition in law; (2) monitor transplantation through certification of centers by the government and health authorities, through certification by surgeons that the donors were indeed dead at the time of organ procurement and that their organs were allocated to recipients by a formal system, through registration of donors and recipients in a database, and through enforcement of standards and regulations for tissue banks; and (3) legislatively forbid commercial organ trafficking. The statement further reiterated the previous councils’ positions that organs should be freely given without commerce, that donor (or family in the case of deceased donors) consent for procurement is mandatory, and that physicians should not be involved with transplantation of organs from executed prisoners (13).

In addition, the 1994–96 Council published another ethics committee report in 1996 (14), confirming that the use of organs from executed prisoners, as reported in 1992 (25), was escalating, with human rights abuses. The report stated that some TTS members had been involved with executed prisoner organ transplants that involved Chinese recipients or sales to foreigners, in violation of TTS principles. The report recognized that at least some Chinese citizens and physicians accepted the practice as ethical, but noted that the Asian Transplantation Society had decreed that organs from executed prisoners should not be used. TTS reaffirmed its opposition to the use of organs from executed prisoners; expressed support for human rights organizations fighting this and related abuses; committed to influencing Chinese surgeons to resist the use of organs from executed prisoners, through open discussions at meetings and through training; and offered assistance to transplant physicians trying to establish programs or policies allowing the use of living and nonprisoner deceased donors whose organs are obtained with proper informed consent. The report was communicated to the Chinese Transplantation Society. TTS opposition to the use of executed prisoners for organ procurement was stated to be independent of individual TTS members’ views on capital punishment, and specific to the circumstances in China. But the report was formulated with the concern that the use of organs from executed prisoners might influence the application of death sentences in any country where capital punishment is legal. The report strongly reaffirmed the policy that transplant professionals not be involved with organs from executed prisoners; that TTS not accept as an affiliate society any society that does not prohibit the use of organs from executed prisoners; that TTS only accept for membership applicants who confirm, by signature, no involvement with executed prisoners; and that TTS remove any members who are involved (14).

Finally, the 1998–00 Council (with Salvatierra as president and A. Benedict Cosimi as ethics committee chair), in a 1999 publication, reaffirmed the 1985 Lancet guidelines and the 1995 Transplantation Society Bulletin statements that “no transplant surgeon team will be involved … in the buying or selling of organs … aimed at commercial gain to himself/herself or an. . . institute” (15). The legal adoption of this policy in the U.S.A. in 1984 was noted. The 1999 publication also reaffirmed this stance: “Organs and tissues should be freely given without commercial consideration or financial profit. . .,” referring to the organ donor (15).

Personally, I think semantic confusion has muddied our discussion of ethical issues (26). There are organ donors (altruistic), and there are organ vendors, but there are no “paid donors.” The adjective “paid” in the context of donation is by definition incorrect, if not an outright oxymoron: there may be brokers or vendors, but a donor does not get paid.

Moreover, an organ “provider” may be neither a donor nor a vendor, but a “conscriptee.” Executed prisoners whose organs are taken for transplantation likely fall into this “conscripted” category of deceased organ providers. There are also stories of living individuals being conscripted to provide organs as well, a practice that is both repugnant and illegal. Societal (legal) conscription of organs from deceased individuals who die under circumstances amenable to procurement has been proposed as one solution to lessen the gap between the need for and the supply of organs for transplantation (27); this would be a step beyond “presumed” consent for donation and akin to mandatory autopsies in “coroner’s cases.” Debate about such proposals is healthy, but the stand of TTS on organ procurement has been consistent for two decades: only donation is acceptable, and informed consent is mandatory (9–15).

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Personal Perspectives

Although the goings-on of TTS in business and ethical matters are important, the scientific progress in the field also deserves attention. I will cite a few advances in clinical application of transplantation that I myself deem just as important as the addition of ever more generalized immunosuppressive drugs to our antirejection armamentarium—maybe even more important. I have attended every international congress of TTS since the third was held at The Hague in 1970. I remember meeting with John Najarian in the coffee shop at the University of Minnesota Hospital after he returned from The Hague and asking him what was new in transplantation. He said, “Well, tolerance and enhancement were shown to be the same thing.” The term enhancement has been out of vogue for years, but at that time, a hot topic was noncytotoxic antibody-mediated suppression of the afferent limb of an immune response to a specific antigen or protection of an allograft from damage by the efferent, or cell-mediated, limb. Several papers were presented on the phenomenon at the third congress and Paul Russell (TTS president, 1970-72; Medawar Prize recipient, 2004) gave an overview of enhancement (28). But Nathan Mitchison, in an overview of immunologic tolerance (29) in a variety of experimental models, laid out compelling evidence that tolerance is not a central failure of an immune response, but rather an active process, with all or many of the variety of reactions seen in the so-called active (as opposed to passive) enhancement models; Mitchison also suggested that the division into two camps (tolerance vs. enhancement) was artificial or semantic. At that time, I was planning my own investigations into the role of passively administered alloantibody, modified to be noncytotoxic, in delaying allograft rejection in an animal model; the insight Najarian brought back from The Hague certainly influenced our interpretations of the effects observed (30). But mainly I remember the coffee shop discussion as a prod to look for a paradigm switch in some area of transplantation during each subsequent congress of TTS.

Although we do not have clinical tolerance, we do have a much lower allograft rejection loss rate today than when TTS began. Indeed, death with a functioning graft has become the most common cause of graft loss—the ultimate goal (what else would we want to be the cause of graft failure?) but with a normal lifespan. Numerous papers have been presented on the reasons for the reduction in graft rejection rates, a reduction usually attributed to the new immunosuppressants. However, I think it is just as likely that the reduction in rejection is due to the development and use of drugs that give effective prophylaxis against opportunistic infections, such as cytomegalovirus (CMV) or Pneumocystis carinii. This anti-infection strategy now allows us to give adequate immunosuppression to prevent rejection with old and new drugs alike. In his presentation at the opening ceremony of our 2004 congress, Starzl stated that we just have to learn how to use the drugs we have better (31). New immunosuppressive drugs keep being developed and then brought to market on the basis of studies showing at least equivalence in effectiveness with the old drugs. But so far, all have been generalized immunosuppressants, and, apart from their nonimmunosuppressive side effects, their limiting factor is the inhibition of the host response to infectious agents.

Transplant clinicians try to minimize the nonimmunosuppressive side effects of antirejection treatments by using a combination of drugs that are additive in their immunosuppressive effects (I find evidence for synergism missing in clinical trials, even though the term is commonly used). However, drugs with distinctly different nonimmunosuppressive side effects—but side effects that are dose-dependent—can be used in combination without an additive effect except for immunosuppression. Thus, such drugs reduce the incidence or severity of side effects without reducing the target level of immunosuppression to prevent rejection; the infectious risk is not altered by the combinations. So, clinicians empirically devise immunosuppressive protocols to minimize nonimmunosuppressive side effects while reaching the desired level of immunosuppression, with the best therapeutic ratio possible, in order to minimize both rejection rates and infection rates. Almost all the abstracts on immunosuppressive protocols report the same rejection loss rates: it therefore is likely that almost all transplant programs immunosuppress at the same level, in spite of the differences in drug combinations chosen. In a sense, all of the drugs are equally potent at a given dose. Clinical trials rarely compare drugs per se, but rather protocols that have to be defined by dose and not just by the drug.

In my opinion, then, the key change that resulted in the reduction of rejection loss rates over the years was not the new immunosuppressants so much as the liberal application of infection prophylaxis. Without such prophylaxis, neither the old nor the new drugs could have been given at the doses necessary to prevent rejection in such a high proportion of allograft recipients.

Clinically, all antirejection protocols seek the same level of immunosuppression: the maximum possible with an acceptable infection rate. As mentioned by Richard Simmons in his Medawar Prize lecture (32), in the early 1970s some programs gave the antimicrobial compound agent trimethoprim/sulfamethoxazole, or its equivalents, indefinitely to kidney transplant recipients. When it became apparent that recipients on the drug rarely developed Pneumocystis carinii or Nocardia infections, its use became widespread. Now, such prophylaxis is simply not mentioned when results are reported, even though it is part of nearly every protocol.

Even more important was the development of synthetic purine nucleoside analogues inhibitory to the herpes family of viruses (33), first acyclovir, and then ganciclovir and valganciclovir. Both of the latter have been particularly effective as treatment and prophylaxis against CMV infection, and the high bioavailability of oral valganciclovir makes clinical application easy. Once identified as the main cause of viral sepsis in the early 1970s, CMV was the bane of transplant recipients until the introduction and especially the liberal use of these drugs (34). The increasing application of ganciclovir and valganciclovir as treatment, but, more important, as prophylaxis against CMV paralleled the reduction in allograft rejection loss rates. I think it likely that the liberal use of antiviral prophylaxis is what made our 1990s results possible. If ganciclovir had been available in the 1970s, we might have had 1990s results then. The nonimmunosuppressive side effect profile would have been different, but anti-T-cell therapy was available then and could have been given to a degree not otherwise possible without antiviral prophylaxis.

Graft survival curves showing improvement in organ allograft survival rate by era are often labeled with the dominant immunosuppressant used at any given period. Yet, one could show the same curves by labeling the eras as pre-gancicolvir, gancicloivir short-term prophylaxis, ganciclovir long-term prophylaxis, and valganciclovir long-term prophylaxis. Of course, we must thank the pharmaceutical industry for the development of a menu of immunosuppressive drugs that has increased the flexibility in antirejection protocols. But of equal, if not more, importance to the improvement in graft survival rates has been the work of our pharmaceutical colleagues in developing effective treatment and prophylaxis against opportunistic infections.

I am confident that the progress against posttransplant immunosuppressant-induced infections will continue. We need to prevent Epstein-Barr virus-induced posttransplant lymphoproliferative disorder, a constant afflicting >1% of transplant recipients (35). We need to conquer the polyoma viruses that have been identified as being responsible for progressive renal allograft dysfunction and failure (36).

Living donors have been a source of kidneys for transplantation from before the founding of TTS, and a source of other organs (e.g., pancreas, intestine, liver, lung) since the founding. But the extent of the use of living donors has changed considerably over the years. Of note is the increased use of unrelated donors and the development of donor exchange programs to achieve blood group and HLA-crossmatch compatibility for recipients who would otherwise have only an incompatible living donor volunteer (37). Living donor transplants across ABO and crossmatch incompatibility have also expanded with neutralizing protocols (e.g., plasmapheresis, intravenous human immunoglobulin administration) (38).

With regard to the use of genetically unrelated living kidney donors, anecdotal information from small series going back to the 1970s suggested that graft survival rates were similar to those of at least mismatched related donor transplants (39). A major impetus to the expansion of such transplants was the registry analysis by Paul Terasaki and colleagues published in 1995 (40). We now know that it is not just a genetic match that promotes graft survival. Rather, a fresh kidney that functions immediately is less likely to incite rejection than one from a deceased donor, regardless of match. The expansion of living donor kidney transplants to over 6,000 annually in the U.S.A. is, in part, attributable to the increased proportion of genetically unrelated donors.

Still, it is the exchange programs that I see as among the most innovative approaches, with potential for application on a large scale. I pay tribute to TTS members who have promoted exchange programs. Kiil Park and his colleagues in Korea, beginning in 1991 (41), were one of the first groups to apply the practice on a large scale (37). This practice not only helps individual patients who otherwise would have to wait for a deceased donor kidney, but also basically shortens waiting time for a deceased donor kidney by reducing the number of patients waiting. The larger the network, the more likely a donor exchange is to materialize, and the bigger the impact on the number of transplants that can be done. National or international networks, coordinated by organizations such as Eurotransplant or the United Network for Organ Sharing, have been very effective in distributing deceased donor organs. But the potential to increase the overall number of organ transplants, particularly kidney transplants, is much greater from the potential living donor pool.

I predict that living donation will increase substantially in the next few years, and that vending will remain illegal—politically not feasible no matter what arguments are made in its favor. In the U.S.A., the annual volume of living donor kidney transplants has tripled in two decades (from <2,000 in the mid-1980s to> 6,000 in the first few years of the 21st century) (42). I predict that the annual rate of living donor kidney transplants will triple again, and in a shorter time. A vending system might also increase the number of kidney transplants, but, again, I do not think a vending system and a donation system can coexist. Directed and nondirected vending would have to coexist, just as is the case for directed and nondirected donation. But we are not going to have antivending legislation rescinded in the countries where organ vending is illegal, and TTS remains opposed to its implementation where it is not. So let us progress with donating and not regress to vending.

My predictions for the near future are that living donor transplants (particularly kidney) will greatly expand; that the pharmaceutical industry will develop antirejection drugs that are purely immunosuppressive, eliminating all side effects except infectious; that prophylaxis against infections that are currently hard to hold in check (such as polyoma virus) will be developed, perhaps to the extent that generalized immunosuppression can be used for xenografts; and that tolerance (eliminating the need for generalized immunosuppression by inhibiting only the antidonor response) will remain as the Holy Grail of transplantation for years to come. If perfected, mechanical organs could eliminate the need for immunologic tolerance, but no current devices (e.g., cardiac assist pumps, closed-loop exogenous insulin infusers) have been good enough to eliminate the queue for organ allografts. Mechanical devices are now used only because of the organ shortage.

I have enjoyed being TTS president and believe that being able to be of service to one’s professional colleagues is a privilege. At the same time, I am glad to pass the baton to Kathryn Wood and focus on my clinical and research activities in beta cell replacement therapy. Gardening is both my hobby and my vocation, whether I am transplanting flowers or human organs. Thank you for the opportunity to share the leadership of TTS with the 2002–04 Council, a wonderful group and so representative of the scientists and humanitarians that comprise our great organization.

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REFERENCES

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