Краткая история клинической трансплантологии
Трансплантация органов - одно из наиболее ощутимых и эффективных достижений XX в. На-
чиная с первых технических неудач в начале века и небольшого количества научных предска-
заний исследователей-провидцев в середине века клиническая трансплантология очень быстро
стала не только практической дисциплиной, но и примером огромных возможностей прогресса
медицинской науки. История трансплантологии изложена в ряде монографий, и хотя в на-
стоящей статье мы не затрагиваем все аспекты исторических событий, было важно выделить
основные моменты, обеспечившие сегодняшний уровень специальности: яркий пример силы
объединения науки и медицины для общего блага.
Ключевые слова:клиническая трансплантация, история
Клин. и эксперимент. хир. Журн. им. акад. Б.В. Петровского. 2017. № 3. С. 7-17.
Статья поступила в редакцию: 01.05.2017. Принята в печать: 15.06.2017.
Данная статья, подготовленная специально для журнала "Клиническая и экспериментальная хирургия", является модифицированной рукописью из руководства Американского общества трансплантологов. Большая часть текста была опубликована в главе Сэра Роя Кална в Руководстве по трансплантации под редакцией доктора Аллана Кирка из Университета Дюка.
Transplantation is one of the most visible and
impactful medical accomplishments of the 20th
century. Arising from technical advances and insights of the early 20th century, the concept that
transplantation was technically feasible gave rise to
earnest investigations into its physiological barriers
by a small number of visionary investigators driven
by recognized clinical problems. From their descriptions of the genetic and immunological basis for graft
rejection and the pioneering work of the first transplant surgeons, the clinical practice of transplantation rapidly became interwoven into the fabric of
clinical care, not only from a practical standpoint but
also as an example of the immense possibilities and
challenges inherent in advanced medical practice.
Multiple concepts now taken for granted in modern
medical practice, such as immunosuppression, monoclonal antibody use, and indeed the concept of death
as a definable state, have their origins in transplantation. Numerous modern ethical quandaries also trace
their roots to problems introduced by transplantation.
The history of transplantation has been the subject of numerous books, and while its in-depth treatment is not practical in this text, it is important to
make evident the major contributions that brought
the field to where it stands currently: a prime example of the power of science and medicine combined
for a common good.
The Concept of Transplant Surgery
The idea of organ transplantation is a surgical
concept based on an understanding of anatomy
and the physiological requirements of an organ to
stay viable and fulfil its biological role. Its origins
relate to intuitive concepts of like replacing like
that date back hundreds of years, including the oft
cited Catholic miracle of Cosmos and Damian. However, its serious pursuit arose independently from
work conducted in a number of European countries
in the early 20th century, the products of which led
to the kidney as the chief candidate for speculations on organ transplantation. Kidney failure was a relatively common fatal condition, the physiological
role of the kidney was understood and the kidneys
were well defined anatomically. Importantly, it was
recognized that one well functioning organ was sufficient to maintain an individual in good health for
a normal lifespan. The kidney’s essential anatomical
connections, namely a single artery and vein and a
urinary drainage vessel, were apparently sufficient
for it to perform its physiological role. Nerves, lymphatic and fascial connections, although important,
did not seem to be essential. At the beginning of the
20th century Alexis Carrel (Fig. 1) devised a method
of joining blood vessels together surgically , a
technique that became the subject of his 1912 Nobel Prize in Physiology or Medicine. Carrel himself
used this technique to show that a kidney could
be removed and transplanted and would function
after restoration of the arterial in-flow and venous
out-flow, provided these surgical procedures were
undertaken expeditiously, since a prolonged period
without a blood circulation led irreversible damage
In cats and dogs Carrel and Guthrie proved the
technical feasibility of the operation and also observed that moving a kidney from an animal to another site in the same animal could result in longterm survival of the kidney and the animal after
removal of the opposite kidney . However, transplanting a kidney from one individual to another,
after a short period of satisfactory kidney function,
was soon doomed to failure. Carrel recorded this observation, but at that time there was no explanation
for the fairly rapid failure of what are now called renal allografts . Priority for the transplantation of
a kidney in a human patient has been claimed and
disputed by a number of surgeons and their historians. Transplants to the brachial or femoral vessels
of human kidneys or animal kidneys to humans were
described. The early claims and a critical discussion
of these unsuccessful experiments can be found in
Francis Moore’s book “Transplant” 1964 ed. Saunders . None of them functioned for a long period of time and with hindsight the procedures were
premature in relation to the knowledge that was
gradually accumulating from Carrel and Guthrie’s
In the 1940-1950s Simonsen and Dempster independently described experiments similar in nature
to those of Carrel and Guthrie and long-term, life-sustaining function of autografts was confirmed.
However, experimental allografts were shown to fail
universally and a second kidney transplanted from
the same donor to the same recipient was destroyed
almost instantaneously. These observations were the culmination of many years of painstaking research by
Morten Simonsen in Denmark and William Dempster
in London who also reported on the use of cortisone
in renal allograft recipients. Both workers described
histological changes that occurred in renal allografts.
The renal cortex became infiltrated with neutrophils,
eosinophils, macrophages, lymphocytes and pyronin- positive plasma cells, and these inflammatory
changes were accompanied by necrosis of nephrons.
Both Simonsen and Dempster felt that it was likely
that the cells originated from the grafted organ and
were in fact a graft-against-host reaction [5, 6]. Subsequently, using a newly developed isotope labelling
technique it was shown by Porter and Calne that most
of the infiltrated cells came from the recipient .
At the time that these experiments were being
performed by Simonsen and Dempster in canine renal
allografts, Peter Medawar (Fig. 2) and his colleagues
had studied the biology of rejection of skin grafts in
rabbits and mice. The first set of grafts became infiltrated with leucocytes after a few days, the graft
becoming necrotic after 7-10 days. A second set of
grafts from the same donor were usually destroyed
immediately and never achieved a capillary circulation. They were called “white grafts”. The immune
nature of skin graft rejection was proved beyond
doubt by Medawar’s group , and from their experiments it seemed likely that kidney grafts between
identical twins would behave like skin grafts between
identical twins and, provided the surgery was satisfactory, would be accepted without any immune reaction. From this scientifically established basis reciprocal skin grafting should differentiate identical from
non-identical cattle twins, and Medawar and his colleagues were confident that this would be straightforward. However, they were astonished and presumably
initially disappointed when the non-identical cattle
twins accepted skin grafts in the same way that grafts
were accepted between identical cattle twins .
They became aware of studies of non-identical cattle
twins by Ray Owen who had observed that non-identical cattle twins frequently had blood groups of more
than one type, circulating in apparently healthy animals . This would be equivalent to a human having some red cells Group A and some Group B, which
was know not to occur because of natural antibodies.
Owen described the unusual status of their red cells
blood groups as “chimeric” from the fanciful resemblance to the mythical ancient Greek animal with organs derived from different species (Fig. 3).
Medawar and his colleagues, Billingham and
Brent, then set about performing a series of carefully
controlled experiments between inbred strains of
mice. The individuals of each strain after many sibling matings would be regarded as identical or “isologous” individuals, so skin grafts were accepted between members of each inbred strain. However, grafts from a given strain transplanted into individuals of a
different strain would be rejected, by what was later
called the “allograft” reaction.
Based on these observations in the cattle twins
Medawar’s group found that injecting cells from one
in-bred strain into the foetus of another strain, although a formidable technical achievement, resulted
in some survivors, which were then rendered “tolerant” to grafts from the strain that donated the tissue (Fig. 4) . They later found that this tolerance
could also be reproduced with neonatal animals,
where the technical challenges were still grave but
less demanding than in the foetus. This discovery
of “specific immunological tolerance” was awarded
the Nobel Prize in Medicine or Physiology and was a
fundamental advance in immunology and also raised
the practical question of whether the plasticity of
the developing foetal immunological system could
be reproduced in an adult, at least temporarily while
a graft was performed, although it would be important that normal immunity would later be restored.
Another factor of importance observed by Medawar’s
group was that if lymphocytes were included in the
donor inoculum they could react against the recipient causing a wasting illness which they called “runt
disease” . This was an example of a graft-versushost reaction, which was subsequently recognized to be extremely important in bone marrow transplantation, and also relevant in some organ transplants,
particularly the liver where many lymphocytes are
transplanted together with the donor liver.
ig. 4. Diagram
of immunological tolerance
experiments by Billing
Brent and Medawar
In the early 1950s David Hume performed a series
of carefully observed clinical kidney grafts, joining
the renal artery and vein to the femoral vessels of the
recipient, bringing the ureter through the skin .
Despite no serious attempt to impair the immunity of
the recipients, some of the grafts functioned and one
continued to produce urine for nearly five months.
When it failed the kidney was found to have both cellular infiltration and severe arteriolar narrowing typical of what later was called “chronic allograft rejection”. The investigators wondered if these somewhat
less severe rejections in human kidneys than those
observed in animal experiments was due to the fact
that the patients all suffered from uraemia, which
was both generally debilitating, but also possibly impaired the normal activity of the immune system.
Concurrently, experimental studies were also performed at the Peter Bent Brigham Hospital in Boston by the departments of surgery under Professor Francis
Moore and medicine under Professor George Thorn.
The surgical experimental lab was headed by Joseph
Murray, a plastic surgeon who had a background in very
intricate surgical correction of dreadful facial deformities (Fig. 5). He brought his skills to the laboratory and
developed an improved surgical technique of kidney
transplantation in dogs, in which the renal artery and
vein were joined to the iliac vessels and the ureter implanted into the bladder, avoiding the discomfort of a
urinary fistula with the concomitant danger of ascending infection. Professor Rene Kuss pioneered the technique of pelvic renal transplantation clinically in Paris
in 1953 when a kidney graft from a mother to son implanted using the pelvic site approach functioned 23
days . This was an important advance in providing
a surgically acceptable procedure.
Fig. 5. Painting
by Joel Babb (1996) of first
identical twin transplant
in Boston 1954
Early Clinical Implementation
In 1954, a patient with renal failure was referred by his doctor to Dr. Merrill, a nephrologist, in Dr. Thorn’s Department with an accompanying note
saying that “you may be interested to know that this
patient is one of identical twins and this could be
relevant to your management”, raising the possibility
that a kidney transplant from the patient’s identical
twin. After careful evaluation of the ethical aspects
and also a demonstration that the twins were in fact
identical by accepting reciprocal skin grafts, the first
identical twin transplant was performed by Dr. Murray
and his colleagues at the Peter Bent Brigham Hospital
and was a spectacular success  (Fig. 6). It showed
that as in animal experiments but also in man, if immunological rejection could be avoided, the surgery
could produce an excellent long-term therapeutic result for the recipient and also the unilateral nephrectomy in the donor would not lead to long-term harm.
For this and his subsequent work, Joseph Murray was
awarded the Nobel Prize in Physiology or Medicine in
1990. Incidentally, the first twin donor survived for
more than 50 years in good health, and served as the
leading edge of follow-up regarding the safety of living donation.
In certain circumstances the original autoimmune cause of renal failure in the recipient recurred in the transplanted kidney, leading to its
demise despite (or perhaps because of) being derived from an identical twin , and this outcome
impelled the search for means of impairing host immunity. In studies on bone marrow transplantation it
had been shown that the immune system of rodents
could be eliminated by a lethal dose of total body X-
irradiation and animals could be rescued by injection
of autologous bone marrow from the same strain.
The bone marrow cells given intravenously homed to
the bone marrow of the recipient and populated, not
only the blood-forming elements, but also the lymphoid cells in the lymph nodes and spleen where they
could restore immunity . If the bone marrow was
not autologous there was danger that the transplant
would fail or if partially accepted, could result in a
fatal graft-against-host reaction. Later developments
in bone marrow transplantation became possible using less severe non-ablative conditioning of the recipient than the original total body irradiation and
has proved to be therapeutically successful, and even
the graft-against-host reaction has been harnessed
as a graft against leukaemia [18, 19].
The success of experimental and clinical bone
marrow transplantation following total body irradiation led to hopes that similar conditioning might be
effective in recipients of kidney grafts. There was one
encouraging result in the dog  but unfortunately
with the exception of two kidney grafts between nonidentical twins, one at the Peter Bent Brigham Hospital and the other in Paris, all the attempts at total
body irradiation failed with disastrous results, rejection not being controlled and overwhelming sepsis becoming a common terminal event [21, 22]. To reduce the toxicity of total body irradiation, repeated
small doses of irradiation to the spleen and lymphoid
organs was developed by Slavin and Strober in Stanford , a technique that continues to be investigated in the pursuit of clinical tolerance.
In the late 1950s it was clear that an alternative superior method would be needed to condition
the recipients of kidney grafts more safely, and an
important pointer was the demonstration that the
anti-leukaemia thiopurine drug, 6-mercaptopurine,
would prevent rabbits challenged with foreign protein antigens from producing antibodies. This ef-
fect persisted after the 6-mercaptopurine treatment
had been stopped and was described by the authors,
Schwartz and Dameshek in 1959, as “drug-induced
immunological tolerance” . 6-mercaptopurine
was then investigated in London at The Royal College of Surgeons of England and in Richmond, Virginia as an immunosuppressant in dogs with renal
allografts, resulting in prolonged allograft survival
but not tolerance [25, 26]. However the effect was
superior to total body X-irradiation. There was a
high incidence of infections caused by the severe
impairment of immune reactions. Hitchings and
Elion, who had synthesised 6-mercaptopurine, provided a number of experimental compounds that
they felt were worth investigating as possibly having a better therapeutic indices than 6-mercaptopurine. One of these agents, azathioprine, was found
experimentally to be slightly superior to 6-mercaptopurine and became an anchor drug for a landmark
series of animal experiments and subsequently for
the next phase of clinical immunosuppression which
was commenced at the Peter Bent Brigham Hospital
. Initial clinical results were disappointing and
it was not until corticosteroids were added to the immunosuppressive regimen that some successes
were obtained in allografts between unrelated individuals . Azathioprine remains indicated for
Steroids had previously been investigated by
Medawar and Dempster, but alone were not very effective. However, when combined with azathioprine,
better results were obtained. Tom Starzl carefully
documented this in Denver, in recipients of renal allografts. Goodwin had already shown that a bolus of
steroids could restore function, at least temporarily,
to a kidney allograft that was undergoing acute rejection [29, 30].
With day-to-day monitoring of patients and adjustment of drug doses to try and find a level that
would prevent rejection without severe toxicity, some
50% of renal allografts were functioning at a year, but
failures were a severe burden for the patients, their
relatives and the surgeons involved. Nevertheless,
during this phase techniques of experimental heart
transplantation were developed by Lower and Shumway in Stanford . Additionally, Starzl in Denver
and Francis Moore at the Peter Bent Brigham in Boston each developed successful surgical techniques for
transplanting the liver [32, 33]. Experimentally head
and limb transplants were performed by Demikov in
Moscow, but at that time these were little more of a
surgical curiosity rather than a serious move forward
towards clinical application .
It became apparent that transplants between
close blood relatives who were not twins had better results than between unrelated donors. The basis for variation was correlated with tissue groups,
which were gradually becoming clarified by Dausset,
Payne, Van Rood and Terasaki [35-38]. These human
leucocyte antigens (HLA) were separate from blood
groups, the typing of which also was required to avoid
immediate graft failure due to preformed antibodies
against red blood cells groups.
Starzl performed the first clinical liver transplants in 1963 . However, the early failure of
these grafts and the demise of the patients led to
Starzl imposing a moratorium until 1967 when he recommenced a liver transplantation programme at the
same time Barnard performed the first clinical heart
transplant [40, 41]. The media excitement towards
the heart transplant was unprecedented in medical
history and led to unfortunate consequences since
all over the world cardiac surgeons attempted clinical
cardiac transplantation “to join the club”. This was
extremely worrying because most of the surgeons had
no background knowledge on the biology of transplantation and the difficulties of prescribing immunosuppressive therapies.
Using aziothioprine and steroids the results
of cardiac and liver transplantation were poor, but
a few patients did very well. Many other agents and procedures were investigated to try and improve immunosuppression. They included total drainage of
lymph from the thoracic duct and ex vivo irradiation
of the kidney and circulating blood. These procedures
were unsuccessful, but the concept of raising antibodies against human lymphocytes proved to be more
promising. This had first been investigated experimentally by Woodruff and colleagues in Edinburgh
in organ grafts after a demonstration of effective antilymphocyte serum produced in rodents to prolong
skin grafts . The antilymphocyte antibodies were
polyclonal, that is they reacted against many different epitopes that were generated when lymphocytes
or thymocytes were injected into a different species,
for example the horse and rabbit. These antibodies
were difficult to purify and tended to vary in efficacy
and toxicity from batch to batch, but some were very
powerful, refined rabbit anti-human thymocyte antibody is still used clinically in patients .
The Modern Era of Immune
In 1978 Borel, an immunologist working in Sandoz laboratories in Basel, Switzerland, described the
immunosuppressive effects of a fungal cyclic peptide, cyclosporine, which was being investigated as
a possible antibiotic . Its antibiotic properties
were weak but its immunosuppressive activity, both
in vitro and in vivo with skin grafts in mice was impressive. On the basis of Borel’s observations we, and
workers at Northwick Park, investigated cyclosporine
in rats transplanted with heterotopic cardiac allografts and found cyclosporine to be extremely ef-
fective [45, 46]. Our studies were extended to canine
renal allografts and orthotopic cardiac allografts in
pigs. In these species, and later in the rabbit, cyclosporine was shown to be a powerful immunosuppressant with few side effects . However, when it was
first used in clinical renal transplants it was found to
be remarkably nephrotoxic, a property that had not
been suspected in the animal experiments . The
nephrotoxicity was particularly severe as the dosage
used in the first clinical trials was based on the animal experiments and found later to be much too high.
Cyclosporine proved to be a watershed in immunosuppression, with the one-year functional survival of
renal allografts increased from 50 to 80%. This early
improvement changed the attitude of the medical
profession towards organ transplantation that previously had been extremely sceptical, and as a result
there were only approximately 10 units worldwide
seriously doing clinical organ transplants. After the
introduction of cyclosporine there were, within a few
years, more than 1000 centres and the anticipated
shortage of organ donors suddenly became a major
consideration, which has escalated ever since.
From Japan the streptomyces-derived compound,
tacrolimus, was developed by the Fujisawa Company
and shown by Ochiai to prolong experimental graft
survival at a very low dosage . After early experimental organ allografts in different species tacrolimus was used in clinical organ transplantation and
fully and exhaustively investigated by Starzl’s group
in Pittsburgh . Tacrolimus has a similar nephrotoxic effect to cyclosporine but the hirsutism and
gum-swelling, which were the common side effects
in cyclosporine-treated patients, did not occur in patients treated with tacrolimus.
The production of monoclonal antibodies by
Kohler and Millstein in 1975 provided an agent with
a single molecular target . This was quickly exploited for use in transplantation, with the development of OKT3, a murine origin monoclonal antibody
specific for the CD3 determinant on T-cells. This
agent effected prompt albeit transient reductions in
peripheral T-cell counts and was shown to reverse established acute rejection . In 1986, OKT3 became
the first monoclonal antibody approved for use in any
human disease, and while its side effect profile, clearance by a mouse-specific antibody response, and the
emergence of other more tolerable therapies, eventually led to its withdrawal from the market, OKT3 served
as a proof-of-concept for the promise of monoclonal
antibody therapy in medicine in general. Similarly,
the concept of humanization, that is genetic engineering of an antibody to make it largely composed
of human structures to avoid a neutralizing antibody
effect, was first launched in transplantation with the
development of daclizumab . As with OKT3, a
completely new therapeutic approach first found its
way into the clinic through transplantation. This drug
also has been removed from modern practice, but others now find their way into our field through off-label
use. Conceptually import in this regard derives from
the work of Waldmann and Winter who developed the
lymphocyte specific humanized monoclonal antibody
Campath 1H or alemtuzumab, an extremely powerful
antilymphocyte antibody that eliminating lymphocytes almost completely from the circulation within
a few hours . It was developed for the treatment
of chronic lymphatic leukaemia but was shown to be
a valuable induction agent in clinical kidney transplant patients, allowing maintenance immunosuppression to be reduced to a significantly low level,
which eliminates most of the toxic side-effects of
maintenance drugs. This concept of powerful almost or “prope” tolerance antilymphocyte induction
therapy followed by very low maintenance does not
generally result in tolerance, but is probably currently
the best available treatment for recipients of organ
grafts [55, 56].
It has been known from the early experimental
liver grafts in pigs and later in rodents, that liver grafts were less severely rejected than other tissue and sometimes were accepted long-term as an
“operational” tolerance in animals not given any
immunosuppression. The transplanted liver often
underwent biochemical and histological rejection,
which recovered spontaneously [57-59] (Fig. 7).
These observations were a background to “experiments” performed by patients in Pittsburgh who
were non-compliant in taking immunosuppression,
without telling their doctors. Some of these patients with liver transplants have survived for more
than 20 years without any immunosuppression
and justifiably would be regarded as operationally
tolerant. Patients in whom immunosuppression
was deliberately stopped or weaned because of infection or as a policy to see if they were tolerant
produced variable results. Some patients accepted
their grafts without deterioration indefinitely, but
others developed rejection and had to return to
immunosuppression. Even an extremely low dose
of immunosuppression may be important in recipients of organ grafts, stopping a very low dose
may lead to rapid rejection which may be difficult
to reverse [60, 61].
A more biological approach to immunosuppression has been studied for some years based on successful murine experiments. Engagement of foreign
tissue with the recipient immune system involves not
only recognition and reaction to antigenic epitopes,
but also a complicated secondary signal that binds
the cells presenting the antigen to the immune reactive cells. The second signal has been studied in great
detail and various methods of blocking the second,
now costimulatory, signal have shown encouraging
results experimentally and have now been investigated in the clinic .
In the past 50 years organ transplantation has
come a long way from a theoretical, fanciful concept
to a fully established practical therapy. There are still
many biological obstacles to be investigated and
overcome, particularly recurrent disease in the transplanted organ, the development of renal damage and diabetes associated with calcinurin-inhibiting drugs
and infection and malignancy, especially lymphoma
and skin cancers. All these unsatisfactory features of
organ transplants have gradually become understood
and various methods of avoiding these side effects
and treating them have been developed. Indeed, and
in depth understanding of these adverse conditions
form the foundation of the knowledge required for
the clinical practice of modern transplantation, and
is approached to some degree in most chapters in
this text. Organ grafting requires surgical expertise but also an ethical framework of compassion and
care (Fig. 8). The success of organ grafts has raised
ethical questions that have emerged like “a can of
worms”, totally unexpected by the pioneers of transplantation in the early days. As the results of organ
transplants improve, so the demand increases, yet the
donor supply does not increase pari passu. There are
not sufficient deceased donor organ transplants in
any country. Indeed, public opinion is often not in favour of deceased donation nor are some governments
prepared to invest in the infrastructure necessary
to educate the public or provide the medical facilities necessary for intensive care of potential donors.
Spain has been the most successful nation in all areas
with deceased organ donation of more than 30 cases
per million but with improved treatment of head injuries and less road traffic accidents than previously,
the “donor pool” has become reduced [63, 64].
Living donors have been used extensively since
the beginning of organ transplantation in identical
twins. Usually the kidney transplantation can be performed ethically between related and unrelated family members and liver transplantation from parents
to children. However beyond these stipulated cases
the ethics of organ donation have been strongly
questioned. Recently a child in China sold his kidney
without his parents knowing to obtain cash to buy
an iPod . Many thousands of patients executed in
China had their organs removed for transplantation.
The transplant community in the West condemns this
practice as unacceptable on a variety of grounds, including the use of organs to generate income from
rich foreign “organ tourists”. Pressure can be put on
individuals to donate within a family and relations
of the patient may feel forced to acquiesce or have a
terrible guilt feeling if they refuse. Attitudes to donation between donor and recipient may change. A New
York surgeon who had given a kidney to his wife, later
divorced her and was awarded considerable damages
in consideration of his previously considered altruistic gift . Liver transplantation from a living adult
donor to another adult has risks that are very difficult to explain to the prospective donor. Not only is
there a high likelihood of prolonged morbidity, but
there is a possibility that organ donation will cause
the donor to lose his or her job and mortality as a
result of the donor operation is high enough to be
considered a significant risk. Five partial liver donors
to adults have been reported to have developed liver
failure themselves, four died and one was rescued
by a transplant . Rich patients may buy organs
illegally. Seldom do the rich donate organs to poor
It is unlikely that the ethical difficulties will
be easily overcome, but defining them is the first
step. In the middle 1960s attempts were made to
transplant organs from animals to man. A variety of well-documented kidney transplants were reported
from New Orleans, Denver, and Richmond, Virginia
and there were also sporadic attempts at other organ
xenografts. To date none have been successful longterm apart from one kidney transplant from a chimpanzee to a patient in new Orleans, which functioned
for nine months, eventually succumbing to chronic
rejection . A great deal of effort has been put
into studying xenograft reaction and defining the
barriers. However, despite intense and expensive experimentation, each barrier appears to be rather like
an opaque hazard in a steeplechase where it is necessary to overcome the first barrier to see the next one
and currently we do not know how many barriers there
are or even if the race can be won.
In a brief period of less than 60 years, transplantation has emerged from its humble origins as an
experimental curiosity to being an accepted means
of life saving therapy for most end organ diseases.
Its success has become increasingly expected, and its
implementation increasingly seen as routine. Survival
of patients with cadaveric kidney and liver grafts for
more than 40 years shows the therapeutic potential
of clinical organ grafting as a life-saving treatment
with restoration to a normal long-term quality of life
In the foreseeable future, despite (or perhaps as
a result of) exceptional advances in overcoming the
surgical and immunological barriers to transplantation, the shortage of organ transplants will remain,
and it is incumbent on the transplant community to
explain honestly the situation to the public and their
governments, and to face the unwelcome fact that not
everybody who might benefit from a transplant will
receive one, this is especially true in poor nations. It
is hoped that as one consumes the specifics of the
expansive practice that is modern day organ transplantation, they will recognize the common thread
that moves through it from fundamental biology and
discovery to similarly fundamental ethical concerns
that define our humanity. In doing so, the student
of transplantation will best appreciate the privilege and responsibility that this field imparts upon
them (Fig. 12).
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