SURGEON GENERAL’S WORKSHOP
ON INCREASING ORGAN DONATION

INTRODUCTION

Historical Perspective on Organ Transplantation and Donation

Antonia C. Novello, M.D., M.P.H., Surgeon General, U.S. Public Health Service,
Washington, D.C.

David E. R. Sutherland, M.D., Ph.D., Professor of Surgery, University of
Minnesota, President, American Society of Transplant Surgeons

Successful organ transplantation is one of the many medical miracles that have
occurred in our extraordinary century. The dream is ancient. The well-known
story of Cosmos and Damian, the martyred twin physicians who replaced the
gangrenous limb of a white sacristan with that of a dead Moor, is visually recorded
by. many artists. However, it was not until the 1900s that scientifically
documented attempts at organ replacement were made, and not until the last half
of this century that success was achieved.

Although there was much faltering along the way, continuous advances in surgical
technique, preservation, immunosuppression, and control of infectious diseases:
have now made success routine, so much so that the demand for human organs
far exceeds the supply. This shortage has prompted a resurgence in
xenotransplantation research (1), an avenue with the potential to lead us full circle.
The first recorded organ transplants in humans (during the first quarter of the
century) were from animal sources (2). All failed immediately. With a few
exceptions (3), so did subsequent transplants from human donors unti! the
landmark identical twin cases carried out at the Brigham Hospital in Boston during
the mid-1950s by Murray, Harrison, Merrill, and associates (4).

Cadaver kidney transplants, however, continued to fail, as did most nonidentical
twin related donor transplants, until the introduction of chemical
immunosuppression in the 1960s (5). When azathioprine and steroids were used
together, reversal of rejection episodes and long-term graft function became
possible (6), feeding the stream that grew into the torrent we see today.

‘The sequential introduction of more effective immunosuppressants (polyclonal
antilymphocyte preparations in the late 1960s and 1970s (7,8), and cyclosporine
(9,10,11) and monoclonal antibodies (12) in the 1980s) were associated with
continuous improvement of results. By the early 1970s, well organized transplant
teams were in place in several institutions, reimbursement for kidney transplants
was assured by Medicare, and liver and heart transplants were beginning to be
successful through the pioneering efforts of Starzl, Calne, Barnard, Shumway, and
others (13-16).

In the 1980s extra-renal organ transplantation came into its own, with a success
rate similar to that of cadaveric kidney transplants (17). By 1990, pancreas
transplant results were also similar to that of the other organs (18).

The number of candidates for transplants of all organs dictates long and sometimes
futile waits. Xenotransplantation has not yet become clinically applicable. There is
a shortage of donors from closely related species (where success can be achieved
in animals), while preformed natural antibodies against the more abundant but
distantly related species remain an impenetrable barrier. Although these problems
may be solvable and warrant vigorous investigational efforts, it is almost certain
that during the next decade clinical transplants will still require human organs.
Therefore, vigorous efforts are needed to increase their supply.

The history of organ donation is complex. As mentioned, the first successful
kidney transplants were from living related donors. Although generally accepted as
a legitimate act of altruism in the United States, there is still controversy over, and
discomfort with, violating the medical imperative "primum non nocere” -- first do
no harm (referring to the donor, of course). Variations in the prevalence of this
attitude are reflected by the different rates that living related donor transplants are
performed throughout the country. Historically, living related donors were
successful because a fresh, undamaged kidney that would function immediately
was available, and the close genetic matches mitigated against rejection during a
time when the immuno-suppressive armamentarium was less than it is today.
Nevertheless, it was apparent early on that it would be necessary to transplant
cadaver kidneys to meet the needs of patients with end stage renal disease.

Many of the first cadaver organs were procured from individuals who were unable
to come off the pump during open heart surgery, and the kidneys were removed
during circulatory and respiratory support. The use of respiratory support systems
for individuals with brain damage ultimately led to the concept and definition of
"brain death.” Formalizing criteria for brain death was necessary both to manage
this tragic situation and to allow removal of organs for transplantation in the
presence of circulatory and respiratory support. The publication of the Harvard
Brain Death Criteria in the late 1960s (19), passage of legislation on the Uniform

- Anatomical Gift Act, evolution of relations between transplant centers and a
network of hospitals and neurosurgeons who would identify brain dead cadaver
donors, and employment of nurses designated specifically to coordinate the
donation process, resulted in the process by which procurement of cadaver organs
hecame a standard procedure throughout the country by the early 1970s. Ad hoc
sharing arrangements were made, organ procurement foundations (e.g., the
Southeast Organ Procurement Foundation) and organ banks (e.g., Midwest)
emerged. By the 1980s, about 2000-3000 brain dead cadavers per year were
utilized for organ transplantation.

The passage of the National Organ Transplant Act in the mid-1980s led to the
creation of the United Network for Organ Sharing (UNOS), standardizing and
formalizing organ procurement agencies throughout the country. Most of them
served more than one transplant center. There was hope that this kind of
organization would, by itself, lead to an increase in organ donation, a hope which
unfortunately was not fulfilled. About 4000 donors per year have been registered
with UNOS from their inception (1986) through the end of the 1980s. Studies by
Bart, et al (20) in the early 1980s indicated that the potential for organ donation
greatly exceeded actual achievement. In two areas of the United States that he
surveyed, only one in six brain dead cadavers were used. Whether the figure is
similar today is not yet known, but new studies are under way. Some cadavers
used in 1980 might not be used today, e.g., those with histories placing them at
risk for HIV. Tests for HIV or hepatitis C were not available in 1980 but they are
today, leading to further (and appropriate) exclusions. Thus, the proportion of
cadavers that would be classified as suitable today may differ from the number
judged suitable at the time of the Bart study. What is certain is that the number of
cadavers used for donation is substantially. less than the potential, and the need to
increase cadaver organ donation is pressing. The potential to increase living
related donation also exists. Strategies to increase donation are intertwined with
ethical, financial, racial, demographic, and other considerations. It is to discuss
and explore these issues that the Surgeon General’s Workshop is convened.

.Over the years many conferences have been held on the many issues involved in
organ donation. The first was sponsored by the CIBA Foundation in 1965 (21).
The extraordinary document that emerged from that conference contains
discussions touching on virtually all the issues that are still of concern to us now,
including living donation and the concept of brain death (the term being first used
at this conference) in cadavers that allows organs to be removed while still under
respiratory support. The issues raised then continue to be debated and many
examples of such debates can be cited (22,23).

The most recent conferences specifically devoted to donor issues include one held
in Munich in December 1990, entitled "Commerce, Ethics and Justice in
Transplantation.” Another, sponsored by the National Kidney Foundation (NKF) in
February 1991 was entitled “Controversies in Organ Donation.” The latter was
designated as a consensus conference and, after intense discussion, issued
Statements on living donation, financial incentives, presumed consent, and minority
donation. (All participants in the Surgeon General’s Workshop should be familiar
with the consensus statements from the NKF Conference.)* In this instance,
“consensus” does not imply complete agreement on all the issues raised, but rather
gives an indication of the evolved thinking of experts over the last 25 years.

However, in general, everyone agrees that efforts are needed to increase the
supply of human organs. Difference of opinion involves only. the means, not the
ends. ,

The purpose of this introduction is not to expand on the background papers for the
workshop, since the papers themselves were designed to be comprehensive. The
first set of papers all address the issue of how to increase donation by focusing on
the individual. Campaigns that reach the general public are needed. In the final
analysis, it is education that will lead to positive attitudes toward organ donation.
Educational efforts must be tailored toward the various socio-economic and cultural
groups that exist in this country. This will be particularly important for increasing
donations among racial groups who are disproportionately affected by the diseases —
for which transplantation is the optimal therapy. For example, blacks comprise
only 12 percent of the total United States population, but they constitute 30
percent of patients on dialysis waiting for a4 kidney transplant. There has been
much publicity about the fact that blacks have received less than 30 percent of
cadaver donor kidneys (24). This is, at least in part, attributable to the fact that
kidneys are distributed according to HLA matching; 92 percent of cadaver kidneys
procured in the United States have come from non-black donors, making a match
less likely. Efforts to increase donation among blacks are being made, but we
clearly cannot expect organ donations greater than their proportion in the
population. Distribution of organs must be made equitable without having 4
negative impact on transplant results. Ultimately the goal should be to improve

~ anti-rejection strategies so that HLA matching becomes less important.

Distribution could then be on a basis other than the chance inheritance of certain
HLA antigens. .

The second set of papers discusses how to increase donation by focusing on the
health care environment. Besides regulatory issues, education of our professional
groups is also needed. Impediments to donation do not always spring from the
attitudes of the families of potential donors, but from environments where donation
is not even discussed. Professional attitudes can make a difference.

A third set of papers discusses donor criteria. The criteria for being 4 donor have
become more stringent - and appropriately so - with regard to assuring against

transmission of diseases such as HIV or hepatitis C. On the other hand, criteria for
being a donor could be more liberal in regard to factors such as age. Arbitrarily

__
* Available on request from The National Kidney Foundation, Inc., 30 East 33rd Street, New York,
ny 10016; (800) 622-9010.
chosen exclusion criteria need to be examined scientifically. The very important
issue of using non-heart beating cadaver donors is also addressed. Most deaths
occur with the cessation of heart beat. Can the logistical aspects be solved to
make these cadavers also sources of organs? These considerations involve legal
and ethical issues. Presumed consent might be necessary for use of non-heart
beating donation to be possible.

Finally, the use of living unrelated as well as related donors is discussed. Some of
us feel that the use of living donors is justified only if the results are superior to
those of cadaver donors, while others think that the use of living donors is justified
if the results are at least equal, as long as there is a shortage of cadaver donors.
Not using living donors is to deny someone a transplant, and why should the
results have to be superior to justify their use? Thus, the debate goes. on.

In summary, this workshop brings together all the groups and disciplines that are
necessary to make transplantation the highly successful enterprise it is today. The
challenge now is to expand the enterprise through increased donations, so that all
who could benefit from transplantation will benefit.

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Department of Health and Human Services, Office of Inspector General.