**3. Historical background**

Organ transplantation and procurement has a rich history, with early accounts of tissue removal and re-implantation involving skin, bone and teeth [8]. During the past several decades, significant progress was made in the area of human transplantation. The evolution of both surgical techniques and immunosuppression resulted in organ transplantation becoming commonplace [9, 10]. Notable medical pioneers of modern transplantation include Dr Christiaan Barnard, Dr Alexis Carrel, Dr Joseph Murray, Dr Thomas Starzl and many others who helped advance the basic scientific and medical understanding required to achieve today's state of knowledge and clinical reliability [11, 12].

From a clinical perspective, the first successful transplants of the modern era involved skin and corneal tissues, and took place in the early 1900s [8]. These experiences, especially involving skin grafting, were plagued by failures well before the concept of tissue compatibility and rejection was fully elucidated [11]. Solid organ transplantation beginning with the kidney was even more challenging. Russian surgeon, Dr Yuri Voronov is credited with the first recorded report of a kidney transplant from a recently deceased donor in the mid-1930s [8, 13, 14]. Although unsuccessful, this procedure foreshadowed the various technical and ethical challenges modern transplantation would face well into the future.

The subsequent years and decades were characterized by a mixture of "trial and error" until the first successful living donor kidney transplant was performed in the mid-1950s by Nobel prize winner, Dr Joseph Murray [8, 11, 13]. The procedure was performed between identical twin brothers, both of whom survived for some time after [15]. Although the understanding of the organ rejection process was still very poor, Murray's successful transplantation strongly implied the need of genetic congruity between donor and recipient. Shortly thereafter, Main and Prehn discovered that chimerism could be induced by using radiation to weaken the immune system of mice, leading to improved acceptance of donor tissue [16, 17]. Several years later, Dr Murray attempted this method in his next successful kidney transplantation, but this was unfortunately preceded by significant mortality among patients who underwent total body irradiation prior to receiving new organs [11, 18]. Of note, this successful non-twintwin transplant recipient was the first well-documented case to recover from rejection [11, 19]. Subsequent failures associated with total body irradiation, including significant morbidity and mortality, led to increased interest in other potential methods of immunosuppression [13].

As a result of intensive research efforts, immunosuppressive medications were soon introduced to help address the problem of graft rejection [20, 21]. Initially the use of monotherapy was attempted with limited effectiveness. It was Dr Thomas Starzl (whose success rates exceeded most in the field at the time) who proposed a cocktail of immunosuppressive agents capable of reversing rejection [11]. This was yet another critical discovery that over time facilitated the expansion of efforts into transplantation of other solid organs, including the first liver transplant in 1963 by Dr Starzl, the pancreas in 1966 by Dr Lillehei and the heart in 1967 by Dr Barnard [8, 22–24]. Although long-term survival of early transplants and their recipients varied, the 1960s ushered in a new era with transplant centers appearing across the world [8, 11, 24]. Organ preservation science developed out of the necessity to ensure organ viability during transport from donor to recipient [25].

Beginning in the early 1900s, Charles Guthrie proposed that cooling of organs may offer a way to preserve them during transport [11]. It was not until the mid-1960s that the use of cooling agents became standard practice with the introduction of the now widely accepted University of Wisconsin solution [11, 26, 27]. With progress being made in multiple aspects of transplantation, new hope arose for patients suffering from various forms of end-stage organ failure. As organ preservation and technical aspects of transplantation advanced, attention shifted to ensuring adequate organ availability [7]. Along with this challenge came the ethical and legal considerations surrounding death and organ donation, which will be addressed in greater detail later on in this chapter.
