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14
A Simple Introduction to Organ Transplant
Dr Gopi Ayyaswamy
The Chinese physician Pien Chi’ao is said to have exchanged hearts
between individuals with different characteristics in an attempt to restore
balance. Similarly, Roman Catholic accounts mention the saints Damian
and Cosmas replacing a gangrenous leg with that of a deceased Ethiopian.
However, these accounts are usually covered in myths and historical
differences.
The outcomes of these procedures, both successful and unsuccessful,
are not well-documented. Centuries later, the Italian surgeon Gasparo
Tagliacozzi achieved success with autografts for skin transplantation but
faced consistent failures with allografts, indicating the presence of rejection
long before its underlying mechanisms were understood. Tagliacozzi
attributed this phenomenon to the “force and power of individuality” in
his work published in 1596.
The history of transplant surgery is marked by signicant milestones
and remarkable achievements, showcasing the progress made in the eld
over the years. Before the scientic understanding and advancements
necessary for successful transplants were established, there are several
intriguing but unveried accounts of early transplants.
As centuries passed, the eld of transplantation continued to evolve. In
the 18th century, a Scottish scientist named John Hunter made a signicant
breakthrough that would shape the course of modern transplantation.
Hunter achieved the rst successful transplantation of a premolar tooth—
an achievement that marked a turning point in the history of surgical
interventions. Revered as the “Father of Experimental Surgery,” Hunter’s
pioneering work laid the foundation for further advancements in the
eld of transplantation. His contributions extended beyond the operating
theatre, as he also coined the term “Transplant,” encapsulating the essence
of this transformative medical practice.
It is important to note that prior to the 20th century, the focus of
transplantation was primarily on the technical aspects—reconnecting
severed limbs, reconstructing noses, and replacing missing teeth.
The intricacies of immunology, the phenomenon of rejection, and the
development of anti-rejection methods would emerge as significant
milestones in the 20th century and beyond. Yet, even as modern science
advanced, ancient mythology continued to serve as a source of inspiration
History of Transplant
15
Dr Gopi Ayyaswamy
and insight in the realm of transplantation and immunosuppression. The
tales of gods and heroes overcoming great challenges and vanquishing
mythical creatures resonate with the spirit of resilience and determination
that permeates the medical community’s ongoing pursuit of knowledge
and breakthroughs.
Through the ages, countless individuals have dedicated their lives to
unravelling the mysteries of transplantation. Their collective efforts, driven
by an unconditional commitment to saving and improving lives, have
propelled the eld forward. As we navigate the complexities of modern
medicine, we stand on the shoulders of these pioneers, drawing inspiration
from their stories and carrying the torch of progress ever forward. Today,
transplantation stands as a testament to the triumphs of human ingenuity,
a testament to the power of ancient wisdom and modern science coming
together to transform lives.
While we celebrate the remarkable achievements of the past, we also
acknowledge that challenges and unanswered questions persist. The quest
for improved outcomes, enhanced immunosuppression techniques, and
expanded access to transplantation remains an ongoing endeavour. As
we forge ahead, driven by the spirit of inquiry and a desire to alleviate
suffering, we honour the legacy of those who came before us, blending
myth and reality in our tireless pursuit of progress.
In 1837, the rst successful corneal allograft transplant was performed in
a gazelle model, followed by the rst successful human corneal transplant
in 1905 by Eduard Zirm. The true breakthrough in organ transplantation
came in 1883 when Swiss surgeon Theodor Kocher conducted the rst
thyroid transplant. By removing the entire thyroid gland, previously
perfected through the removal of excess tissue in goiter cases, Kocher
observed a complex of symptoms associated with a lack of thyroid
hormone. He reversed these symptoms by implanting thyroid tissue, thus
pioneering organ transplantation.
Following the thyroid’s success, other organs, such as the adrenal
and parathyroid glands, pancreas, ovary, testicles, and kidney, were
also transplanted. The early 1900s saw signicant progress in transplant
surgery techniques, with French surgeon Alexis Carrel and his colleague
Charles Guthrie developing skilled anastomosis operations and suturing
16
A Simple Introduction to Organ Transplant
Dr Gopi Ayyaswamy
techniques. Their work laid the foundation for future transplant surgeries
and earned Carrel the Nobel Prize in Physiology or Medicine in 1912. In
subsequent years, transplant experiments were conducted on animals,
contributing to the understanding of organ functions and the identication
of rejection issues.
During World War I, signicant advancements in skin transplantation
were made by Harold Gillies, who introduced the tubed pedicle graft
technique. His work continued into World War II with reconstructive
surgery led by his assistant, Archibald McIndoe. In 1962, the ground
breaking achievement of replantation surgery was accomplished by
reattaching a severed limb and restoring limited function and sensation.
The first transplant of a single gonad (testis) from a living donor
took place in 1926, performed by Russian surgeon Dr. Peter Vasil’evič
Kolesnikov. However, legal charges were brought against Kolesnikov for
deceiving the donor, who believed his act of donation had commuted his
death sentence.
The first attempted deceased-donor transplant was conducted by
Ukrainian surgeon Yuri Voronoy in the 1930s, but it ended in failure due
to rejection. The rst successful transplant took place in 1954 when Joseph
Murray and J. Hartwell Harrison performed a kidney transplant between
genetically identical twins, eliminating the need for immunosuppression.
In the late 1940s, Peter Medawar contributed to the understanding
of rejection by identifying immune reactions and proposing the use of
immunosuppressive drugs. Cortisone and azathioprine were subsequently
discovered, but it was the introduction of cyclosporine in 1970 that provided
a powerful immunosuppressive agent, revolutionizing transplant surgery.
The quest for heart transplantation faced numerous challenges,
including the issue of rapid heart deterioration after death and the need
for a heart-lung machine. James Hardy attempted the rst human heart
transplant in 1964, using a chimpanzee heart due to the unavailability of a
human donor. However, it quickly failed. The rst successful human heart
transplant took place on December 3, 1967, performed by Christian Barnard
in South Africa. Although the recipient, Louis Washkansky, survived for
only eighteen days, the achievement sparked widespread media interest
and initiated a wave of heart transplants.
History of Transplant
17
Dr Gopi Ayyaswamy
The advent of cyclosporine in 1968 transformed transplants from
experimental procedures to life-saving treatments. Denton Cooley
performed 17 transplants, including the rst heart–lung transplant, but
the majority of his patients succumbed within six months. By 1984, two-
thirds of heart transplant patients survived for ve years or more.
With the increasing success of organ transplants and the development
of modern immunosuppression techniques, the need for more organs
became critical. Living-donor transplants, particularly from relatives,
became more common. Researchers also explored the possibilities of
xenotransplantation, using transgenic or genetically modied organs,
although clinical trials in humans are yet to be widely implemented.
Efforts are underway to reduce the burden of immunosuppression
and develop new drugs for transplantation. Strategies such as avoiding
steroids, minimizing exposure to calcineurin inhibitors, and tailoring drug
regimens based on patient outcomes and function are being explored.
While short-term outcomes show promise, the long-term effects and risks,
including rejection and infection, need further investigation.
The field of regenerative medicine holds potential for solving the
problem of organ transplant rejection by growing organs in the laboratory
using a person’s own cells, such as stem cells or healthy cells derived from
the donor site. This emerging eld offers a promising avenue for future
advancements in transplantation.
The history of transplant surgery showcases the remarkable progress
made over time, from early attempts with limited understanding to life-
saving procedures that have become increasingly commonplace. Ongoing
research and technological advancements continue to push the boundaries of
transplantation, providing hope for patients in need of organ replacements.
Many other new drugs are under development for transplantation. The
emerging eld of regenerative medicine promises to solve the problem of
organ transplant rejection by regrowing organs in the lab, using person’s
own cells (stem cells or healthy cells extracted from the donor site).
Timeline of Successful Transplants
1823: First skin autograft-transplantation of skin tissue from one
location on an individual’s body to another location. In a method
18
A Simple Introduction to Organ Transplant
Dr Gopi Ayyaswamy
very reminiscent of Sushrutha’s, Carl Bunger, a German surgeon
documented the rst modern successful skin graft on a person with a
nose destroyed by syphilis. He grafted a small chunk of full thickness
esh from the inner thigh to the nose successfully.
1905: First successful cornea transplant by Eduard Zirm (Czech Republic)
1908: First skin allograft—transplantation of skin from a donor to a
recipient (Switzerland)
1933: First successful cadaveric AB-0 incompatible kidney transplant
(donor was B(III) and the recipient has 0(I)) by Yuriu Yu. Voronoy (USSR)
1950: First successful kidney transplant by Dr Richard H. Lawler (Chicago,
USA)
1954: First living related kidney transplant (identical twins) (USA)
1955: First heart valve allograft into descending aorta (Canada)
1962: First kidney transplant from a deceased donor (USA)
1965: Australia’s first successful (living) kidney transplant (Queen
Elizabeth Hospital, SA, Australia)
1966: First successful pancreas transplant by Richard Lillehei and William
Kelly (Minnesota, USA)
1967: First successful liver transplant by Thomas Starzl (Denver, USA)
1967: First successful heart transplant by Christian Barnard (Cape Town,
South Africa)
1981: First successful heart/lung transplant by Bruce Reitz (Stanford,
USA)
1983: First successful lung lobe transplant by Joel Cooper at the Toronto
General Hospital (Toronto, Canada)
1984: First successful double organ transplant by Thomas Starzl and Henry
T. Bahnson (Pittsburgh, USA)
1986: First successful double-lung transplant (Ann Harrison) by Joel
Cooper at the Toronto General Hospital (Toronto, Canada)
History of Transplant
19
Dr Gopi Ayyaswamy
1995: First successful laparoscopic live-donor nephrectomy by Lloyd
Ratner and Louis Kavoussi (Baltimore, USA)
1997: First successful allogeneic vascularized transplantation of a fresh
and perfused human knee joint by Gunther O. Hofmann
1997: Illinois’ rst living donor kidney–pancreas transplant and rst robotic
living donor pancreatectomy in the USA University of Illinois Medical
Center
1998: First successful live-donor partial pancreas transplant by David
Sutherland (Minnesota, USA)
1998: First successful hand transplant by Dr Jean-Michel Dubernard (Lyon,
France)
1998: United States’ first adult-to-adult living donor liver transplant
University of Illinois Medical Center
1999: First successful tissue engineered bladder transplanted by Anthony
Atala (Boston Children’s Hospital, USA)
2000: First robotic donor nephrectomy for a living-donor kidney transplant
in the world University of Illinois Medical Center.
2000: Indian surgeon Dr. Mohamed Rela, earned a spot in the Guinness
Book of Records for his remarkable achievement of performing a successful
liver transplant on an infant aged only 5 days. Furthermore, he holds a
track record of conducting over 4,000 liver transplantations.
2004: First liver and small bowel transplants from same living donor into
same recipient in the world University of Illinois Medical Center.
2005: First successful ovarian transplant by Dr PN Mhatre (Wadia Hospital,
Mumbai, India)
2005: First successful partial face transplant (France)
2005: First robotic hepatectomy in the University of Illinois Medical Center.
2006: Illinois’ rst paired donation for ABO incompatible kidney transplant
University of Illinois Medical Center.
2006: First jaw transplant to combine donor jaw with bone marrow from the
patient, by Eric M. Genden (Mount Sinai Hospital, New York City, USA)
20
A Simple Introduction to Organ Transplant
Dr Gopi Ayyaswamy
2006: First successful human penis transplant (later reversed after 15 days
due to 44-year-old recipient’s wife’s psychological rejection) (Guangzhou,
China)
2008: First successful complete full double arm transplant by Edgar Biemer,
Christoph Höhnke and Manfred Stangl (Technical University of Munich,
Germany)
2008: First baby born from transplanted ovary. The transplant was carried
out by Dr Sherman Silber at the Infertility Centre of St Louis in Missouri.
The donor is her twin sister.
2008: First transplant of a human windpipe using a patient’s own stem
cells, by Paolo Macchiarini (Barcelona, Spain)
2008: First successful transplantation of near total area (80%) of face,
(including palate, nose, cheeks, and eyelid) by Maria Siemionow
(Cleveland Clinic, USA)
2009: Worlds’ rst robotic kidney transplant in an obese patient University
of Illinois Medical Center.
2010: First full facial transplant by Dr. Joan Pere Barret and team (Hospital
Universitari Vall d’Hebron on 26 July 2010, in Barcelona, Spain)
2011: First double leg transplant by Dr Cavadas and team (Valencia’s
Hospital, La Fe, Spain)
2012: First Robotic Alloparathyroid transplant. University of Illinois
Chicago.
2013: First successful entire face transplantation as an urgent life-saving
surgery at Maria Skłodowska-Curie Institute of Oncology branch in
Gliwice, Poland.
2014: First successful uterine transplant resulting in live birth (Sweden)
2014: First successful penis transplant. (South Africa)
2014: The United Kingdom accomplished its rst successful organ donation
from a newborn to an adult.
Dr Gopi Ayyaswamy
Organ Transplantation
4
Organ transplantation is the moving of an organ from one body to another
or from a donor site to another location on the person’s own body, to
replace the recipient’s damaged or absent organ. The emerging eld of
regenerative medicine is allowing scientists and engineers to create organs
to be re-grown from the person’s own cells (stem cells, or cells extracted
from the failing organs). Organs and/or tissues that are transplanted
within the same person’s body are called autografts. (Source: WHO &
Medical Literature).
Transplants that are recently performed between two subjects of the
same species are called allograft. Allograft can either be from a living or
cadaveric source. Organs that can be transplanted are the heart, kidneys,
liver, lungs, pancreas, intestine, and thymus. Tissues include bones,
tendons (both referred to as musculoskeletal grafts), cornea, skin, heart
valves, nerves and veins. Worldwide, the kidneys are the most commonly
transplanted organs, followed by the liver and then the heart. Cornea and
musculoskeletal grafts are the most commonly transplanted tissues; these
outnumber organ transplants by more than tenfold.
Organ donors may be living, brain dead, or dead via circulatory death.
Tissue may be recovered from donors who die of circulatory death, as well
as of brain death—up to 24 hours past the cessation of heartbeat. Unlike
organs, most tissues (with the exception of corneas) can be preserved and
stored for up to ve years, meaning they can be “banked”.
Transplantation raises a number of bioethical issues, including the
denition of death, when and how consent should be given for an organ
22
A Simple Introduction to Organ Transplant
Dr Gopi Ayyaswamy
to be transplanted, and payment for organs for transplantation. Other
ethical issues include transplantation tourism and more broadly the socio-
economic context in which organ procurement or transplantation may
occur. A particular problem is organ trafcking. Some organs, such as
the brain, cannot be transplanted. Transplantation medicine is one of the
most challenging and complex areas of modern medicine. Some of the key
areas for medical management are the problems of transplant rejection,
during which the body has an immune response to the transplanted organ,
possibly leading to transplant failure and the need to immediately remove
the organ from the recipient. When possible, transplant rejection can be
reduced through serotyping to determine the most appropriate donor-
recipient match and through the use of immunosuppressant drugs.
Topics to Ponder
1. Types of transplant
2. Transplantable organs and tissues
3. Types of donor
Types of Transplant
• Autograft
• Allograft and allotransplantation
• Isograft
• Xenograft and xenotransplantation
• Split transplants
Autograft
Autografts refer to the transplantation of tissue within the same
individual’s body. This procedure is often employed using excess tissue,
regenerative tissue, or tissues that are urgently needed in other areas of
the body. Examples of autografts include skin grafts, where healthy skin is
transplanted to an area in need of healing, and vein extraction for coronary
artery bypass grafting (CABG), where veins from the patient’s own body
are used to bypass blocked arteries.
Organ Transplantation
23
Dr Gopi Ayyaswamy
In certain cases, an autograft involves removing tissue from the person’s
body, treating it or the individual, and then returning it to its original
location. For instance, stem cell autografts involve harvesting and utilizing
the person’s own stem cells for therapeutic purposes, and blood may be
stored in advance of surgery to be later transfused back into the patient.
Another variation of autografting is rotationplasty, which involves
replacing a more proximal joint (such as the knee) with a distal joint (like
the foot or ankle). In this procedure, the person’s foot is surgically severed,
rotated, and then attached to the remaining bones of the leg (the tibia and
femur) to function as the new joint.
Allograft
An allograft refers to the transfer of an organ or tissue from one individual to
another within the same species, specically when they are not genetically
identical. In the context of human transplants, the majority of tissue and
organ transfers fall under the category of allografts. It is important to note
that since the organ or tissue being transplanted is genetically distinct from
the recipient, the recipient’s immune system recognizes the transplanted
material as foreign and initiates a defensive response to eliminate it. This
immune response is known as transplant rejection. To assess the likelihood
of transplant rejection, medical professionals often evaluate the recipient’s
Panel Reactive Antibody (PRA) level. This measurement provides an
estimation of the recipient’s immune system’s reactivity towards donor
antigens, which can help gauge the potential risk of rejection following
an allograft procedure. By monitoring and analyzing the PRA level,
healthcare providers can make more informed decisions regarding
immunosuppressive treatments and other strategies to minimize the risk
of rejection and optimize the chances of a successful transplant outcome.
Isograft
Isografts represent a unique category within the broader field of
transplantation, specically involving the transfer of organs or tissues
from a genetically identical donor to a recipient. This type of transplant is
most commonly observed in cases of identical twins, where the donor and
recipient share the same genetic makeup. What distinguishes isografts from
other types of transplants is their remarkable ability to avoid provoking