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together to ensure that the blood would keep contact with the smooth inside of the vessel (endothelium).
This and the use of strict asepsis to avoid infection allowed him to develop the techniques further by mov-
ing hearts, kidneys and spleens during experiments in dogs and also allowed other groups to begin experi-
mentation in animal models of transplantation. Carrell famously noted that despite success in the technical
aspects of transplantation, there were consistent hostile host responses to the foreign allografts especially
[12]
during xenotransplantation .

“Should an organ, extirpated from an animal and replanted into its owner by a certain technique, continue
to functionate normally, and should it cease to functionate normally when transplanted into another ani-
mal by the same technique, the physiologic disturbance could not be considered as brought about by the
organ but would be due to the influence of the host, that is, the biological factors”.

Despite Carrell’s observations, between 1905-1910, several surgical peers such as M Princeteau, Mathieu
Jaboulay and Ernst Unger in this era attempted xenotransplantation of rabbit, pig and macaque kidneys to
[13]
humans with disastrous results .

PRE-IMMUNOSUPPRESSION ERA
Leo Loeb first noted that the strength and timing of rejection in skin homografts on rodents was potentially
caused by genetic disparity between donor and recipient and highlighted the involvement of lymphocytes in
[14]
the 1930s . He theorised that this genetic disparity did not occur in identical twins thus they would accept
exchanged skin grafts. Unfortunately, his findings were ridiculed due to his inbreeding of mice. Contempo-
raries such as Peter Medawar dismissed the importance of lymphocytes and adopted the humoral theory of
[14]
rejection . The ensuing two decades were fraught with failed attempts of kidney transplantation in both
human and animal models by Voronoy (1937), Simonsen (1953) and Dempster (1953) who even used radia-
[15]
tion in organ transplant recipients . Medawar’s renewed interest in transplant rejection brought him to the
Burns Unit at Glasgow Royal Infirmary (Gibson and Medawar, 1943) with Thomas Gibson. He remained
[16]
convinced that skin grafts in burn victims failed because of humoral rather than cellular immunity . His
work with Rupert Billingham and Hugh Donald revealed that even fraternal twin cows accepted skin grafts,
[17]
not just identical twin cows . Across the Atlantic, Ray Owen at the University of Wisconsin noted a hybrid
of blood cell types in fraternal twins. He concluded that there was persistence of chimerism from the in-
[14]
trauterine transfer of stem cells which was probably responsible for this . Medawar, Billingham and Leslie
Brent induced chimerism and homograft acceptance in mice by injecting inoculating intrauterine fetuses
[18]
with donor strain spleen cell . This was ultimately successful and resulted in a Nobel Prize in 1966 for Peter
Medawar. They later discovered that some of the immunocompetent cells from the splenic tissues “attacked”
the lymphoid tissue of the host (Graft-Versus-Host-Disease), thereby proving the role of cellular immunity as
[14]
first theorised by Loeb .
Meanwhile, Joseph Murray and his team performing the first successful kidney transplant in 1954 using as
[19]
a donor the recipient’s identical twin bypassing the issues with immunity . This generated a lot of interest
in the field of transplantation. Joan Main and Richmond Prehn attempted to recreate Medawar’s stem cell
inoculation. They radiated mice to allow induction of bone marrow from a donor. Murray’s team used this
method with poor outcomes as 11 of the 12 patients who underwent kidney transplantation with total body
[14]
irradiation died within a month . The survivor maintained adequate function of his fraternal twin’s kidney
for 20 years thereby becoming the first successful non-identical twin kidney transplantation. Jean Ham-
burger and René Küss from Paris performed 4 successful transplants using total body irradiation without
[15]
marrow inoculation .