The history of transplantation is a scientific journey that describes the medical community's efforts to understand how the human body works. Humans have long realized the possibilities that transplantation of organs and tissue provides. Throughout history, people have always been intrigued by the possibilities of transplantation of organs and tissues. In the 6th Century BC Indian surgeons described how to reconstruct facial wounds by transplanting the skin from one place on the body to the other. During the middle age there were many references in the historical medical literature of attempted blood transfusions as well as the transplantation of teeth. A skin transplant and a corneal transplant were reported in medical journals dating back to 1880. These early attempts were usually unsuccessful. Early in the twentieth century transplantation started to offer the promise of restored health and life. One of the exceptional medical advances of the twentieth century, organ transplantation has become a routine treatment for patients with organ failure which was a goal.
Introduction
The meaning of the history of transplantation is important because the transplantation represents the beginning into advanced clinical medicine. In the 20th century we experienced an explosion in the discovery of human organisam and patology and transplantation is a new chapter in the reasurch and clinical application of discoveries for the benefit of the human being. (1)
The history of transplantation is a story about science whose application could not be fereseen at the start of the century. She is a result of years of cooperation between scientist and clinical personnel, both of which contributed to the salving of the puzzle, each in their respective fields. This is a fascinating story about modern surgery, which changed and will continue to change the final outcome of numerous conditions.(2)
The beggining of transplantation of organs
The idea of transplantation was always a big interest of medical researchers, but it is very hard to establish date when that idea was born. Many written documents from ancient Greek medicine expressed suspicious about the idea that transplantation of organs could become reality. Professional distinction between surgeons and doctors in ancient Greek was the main reason for that attitude (3).
Sushruta (6th century BC) was a renowned surgeon of ancient India, and the author of the book Sushruta Samhita. In his book, he described over 120 surgical instruments, 300 surgical procedures and classified human surgery into 8 categories.(4)That is the one of the oldest documents in Buddhist religion that deals with transplantation of organs. This material was about evaluation of level of knowledge and experience of surgeons who were capable to start transplantation. In these documents for the first time were mentioned medical sciences that should be involved in transplantation like, anatomy, physiology and pathology. Ancient Greek translated Samhita Sushruta and his work was analyzed by Hipokrat who often quoted him in his works.(5,6) Besides Sushruta ancient Greeks and Hipokrat were analyzing another great Hindu writer Kashmiri whose handwritings were about rhino plastic and surgery. Hipokrat himself was very involved in ethical and technical issues of transplantation. In his handwritings he comprehensively described surgical complications in operations of nose, ear, mouth etc.(7)
Egyptians overtook this method and well known Alexandria school was established. The greatest writers of that time were Hazes 924a.c. and Albucasis of Cordova 1013a.c. These famous Arabian writers highlights this era of progressive Arabian medicine.(8)
He work on transplantation, regeneration of tissue and rhino plastic. He affirmed usage of free grafts which earlier methods disproved. Further more, Wolf and Thiersch achieved great results in infection prevention at skin transplantation. They realized that skin grafts don't need to contain subcutaneous tissue and that was their great achievement. In his experimental models Thiersch succeeded to prove that transplantation of skin from other species to human is not possible and transplant usually get rejected. Thirsch also gave an explanation for that graft rejection: reasons for graft rejection are in incompatibility between tissues.(15,16)
Development of blood transplantation from human to human also gave new hopes in field of organ transplantation. First doctor who made a machine for blood transplantation was English doctor James Blundell gynecologist and had a few cases of successful transfusion while delivering patients with excessive hemorrhaging. These cases bring lot of optimism between doctors of that time but at the same time post transfusion reactions gave certain insecurity (17) These negative reactions with temperature and fever resulted in abandon transfusion from animals to human and improve human to human transfusion techniques. In 1900 Erlich discovered that erythrocytes in blood transfusion, can act provocative in creating isohaemolisin or hemolytic antibodies. Landsteiner provided more detail explanation about who discovered mechanisms of that reaction and described these antibodies as anti E and anti B proving their bounding on erythrocytes of graft recipient.(18) For this discover Landsteiner was awarded with Nobel price for Medicine on the field of blood transfusion. That was a base for starting new era of transplantation. This improved understanding of basic immunological mechanisms and interactions of antibodies and need for further exploring of immunology was awakened. The result of that was discovery of role of lymphocytes cytotoxic antibodies and understanding of cross match reactions as base of histocompatibility of organs for transplantation.(19)
John Hunter 1728-1793 was a pioneer in the field of transplantation. He discovered that transplanted organ must have same conditions as in his natural environment as soon as possible. He described his experience in experiment with teeth, he transplanted teeth and discovered that transplanted organ needs supply of fresh blood in short period of time and that is condition for organ to survive. These principles are caped until today. Brown Sequard fallowed his steps and explored recovery of function of nervous system of transplanted organs. He improved discoveries of John Hunter and was rewarded by French Academy of Science. His experiments of isolation of organs form corps that he isolated and defibrinated in blood on 19 C degrees, 13 hours after dead. This kind of muscle preservation ensured that muscles have same answer on stimulation even after transplantation. In 20th century some of the postulates of Hunter theory were reborn.(20,21)
Transplantation of the 20th century
In beginning of 20th century there are also some American doctors John Davis and John Hopkins who published their results mostly in xenotransplantation. In their experimental transplantation they wanted to learn more about experiments and which mechanisms are supporting or obstructing it.
Joseph Lister pioneered the field of aseptic surgery based on Louis Pasteur's advancement of bacteriology. It was helpful for prevention of sepsis and brought to decreasing level of infection of transplanted organs in operating rooms.(22) Big problems for surgeons during the transplantations were complications as thrombosis, aneurism bleeding etc. This was improved after Second World War introducing fine surgical monofilament fiber which prevents these complications and insured safer anastomozing of the blood vessels of transplanted organs. Discovery of heparin as very potent anticoagulant in 1960 reduced complications such as thrombosis and embolism.(23)
Introducing of direct artheriography as very important diagnostic method for blood vessels insured preventions of complications in posttransplantation period. Also usage of special grafts for angioplasty increased results of transplantation.
Figure 1.Alexis Carrel (1873-1944) Nobel Price for medicine in 1912
Figure 2.Theodor Kocher (1841-1917) Nobel Price for medicine in 1909
Famous names of that time in surgery were Morel, Murphy and Carrel (figure 1.) who is known as the founding father of experimental organ transplantation because of his pioneering work with vascular techniques (24) Theodor Kocher (figure 2.) was famous in extirpation and transplantation of thyroid gland. The American Charles Guthrie and Carrel transplanted dogs head on others dog shoulders in 1954. In that time Nobel price in field of transplantation was won by Leonardo Hill.(25) That price was subject of many discussions because that should be won by Carrel and Guthrie who, according to Medical Public of these days had better results of improvement of blood anasthomosis in transplantation. The techniques used to join the vessels together were those developed and described by Alexis Carrel, who had been a young surgeon in Jaboulay's unit, and in fact, the techniques of vascular anastomosis described by Carrel are exactly those still used in renal transplantation today.(26) Carrel subsequently moved to the Rockefeller Institute in New York, but he continued his organ-transplantation work until the beginning of the First World
War. Indeed, in a prescient lecture in 1914, he said that the technical problems of transplantation were essentially solved, but until some method was developed to prevent the reaction of the organism against the foreign tissue, there would be no clinical application of organ transplantation. Between the wars, experimental transplantations were occasionally performed, but there was no advance in knowledge. There was a serious clinical attempt by a Russian surgeon, Yu Yu Voronoy, who transplanted cadaveric kidneys into six human recipients, but without success.(27,28)
The modern era of clinical transplantation began in Paris and Boston after the Second World War, and one highlight of postwar efforts was the small series of transplantations of cadaveric kidneys performed by David Hume at Peter Bent Brigham Hospital in Boston. No immunosuppression was used, but some kidneys did function for days or weeks, and one for several months — no doubt because of the immunosuppression resulting from the profound uremia in the recipients.(29) Enormously encouraged by the successful transplantation between identical twins that had shown that renal failure could be reversed completely, those pursuing immunosuppression, in Boston and Europe, now directed all their efforts at total-body irradiation.
Although such irradiation did achieve immunosuppression, however, it also produced profound marrow aplasia, which led to patients' deaths from overwhelming infections. By the early 1960s, it was clear that total-body irradiation was not the solution.(30)
During the early stages of the Second World War Peter Medawar was asked by the Medical Research Council to investigate why it is that skin taken from one human being will not form a permanent graft on the skin of another person, and this work enabled him to establish theorems of transplantation immunity which formed the basis of his further work on this subject.(31) When he moved to Birmingham in 1947 he continued to work on it, in collaboration with R. Billingham, and together they studied there problems of pigmentation and skin grafting in cattle, and the use of skin grafting to distinguish between monozygotic and dizygotic twins in cattle.(32,33)
Figure 3. Double organs transplantation pancreas and kidney
Medawar (figure 4.) was Nobel Prize awarded in 1960 with Burnet for their work in tissue grafting which are the basis of organ transplants, and their discovery of acquired immunological tolerance. This work was used in dealing with skin grafts required after burns. Medawar's work resulted in a shift of emphasis in the science of immunology from one that attempts to deal with the fully developed immunity mechanism to one that attempts to alter the immunity mechanism itself, as in the attempt to suppress the body's rejection of organ transplants.(34,35,36)
Figure 4. Peter Medawar (1915-1987) The Nobel Prize in Physiology or Medicine 1960
Conclusion
Modern medicine has triumphed over many challenges and overcome many hurdles to achieve successful organ transplantation. The goal of organ transplantation is to provide the patient with an active and happy life, instead of the untimely death from fatal disease of a vital organ. Today the transplantation has become a massive field. The great advancement of medicine has enabled us, through the transplantation of organs, to minimize the death rate and minimize the enormous material expenditure in society.
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Corresponding author:
Prof. Jasenko Karamehić MD, Clinical Center University of Sarajevo, Bosnia and Herzegovina, Institute of Immunology, Bolnička 25, tel: 00 387 33 297 304, [email protected]
Thank you professor Karamehic for this interesting question and statement, and for providing us with this interesting history path that transplantation had through history. I would also agree with this, that Transplantation is one of the greatest achievents in history of medicine.
Thank you for your opinion, which is very useful to me and also thank you for a successful cooperation!
Since you are very experienced in organ transplantation and an expert in this field, could you please provide me with information about what do you think about future resources of organs in organ transplantation? Resources are limited now and it is a big problem in organ transplantation.
Very good and remarkable and logical question! That existing resources are really not enough for a large number of candidates who are located around the candles on waiting lists enabling appropriate donors!
According to some data statistakama in the world 25 percent of patients never get the appropriate authority and die on the waiting list!
One way of attempting to overcome this problem no light problem is the development of new immunosuppressive drugs in order to overcome immunological barrier to xenotransplantation as one of the possible new sources of authority in the future!
I forgot to mention that in addition to xenotransplantation as a possible source of organs for transplant, you should consider the option of redesigning artificial organs that have one big advantage over ksenotranslantation and it is causing much lower immune response!
Also realistic option is the development and use of stem cells for transplant needs!
Due to limited resources for donating organs, what do you thing abbout the sources of organs in the future?
Through the history of transplantation, which years do you find most successful?
I repeat my answer previously given by distinguished professors Jozo Coric and thank to set a very interesting feature issue that is crucial for the development of transplantation:
Very good and remarkable and logical question! That existing resources are really not enough for a large number of candidates who are located around the candles on waiting lists enabling appropriate donors!
According to some data statistic in the world 25 percent of patients never get the appropriate authority and die on the waiting list!
One way of attempting to overcome this problem no light problem is the development of new immunosuppressive drugs in order to overcome immunological barrier to xenotransplantation as one of the possible new sources of authority in the future!
Transplantation of organs one of gratest achievement in history of medicine. Available from: https://www.researchgate.net/post/Transplantation_of_organs_one_of_gratest_achievement_in_history_of_medicine#view=5927d9973d7f4b435b71a9cc [accessed May 26, 2017].
I forgot to mention that in addition to xenotransplantation as a possible source of organs for transplant, you should consider the option of redesigning artificial organs that have one big advantage over ksenotranslantation and it is causing much lower immune response!
Also realistic option is the development and use of stem cells for transplant needs!
Transplantation of organs one of gratest achievement in history of medicine. Available from: https://www.researchgate.net/post/Transplantation_of_organs_one_of_gratest_achievement_in_history_of_medicine#5927e48bcbd5c2ad4774ba6d [accessed May 26, 2017].
Answer dr.Marina -Delic,
All those years when he started the first kidney transplant in 1954 in the hospital, Peter Bent Brigham .Boston, USA!
Next, When the first individual organs transplantation between 1960-1970 transpntacije started when the liver, heart,
bone marrow. Pancreatic ..... then it is very important 1980 years of the discovery of Cyclosporine excellent immunosuppressant, who has made a real revolution in the advancement of organ transplantation etc. disproportionate later years when they discovered monoclonal antibodies as very modern immunological therapy in the prevention of graft rejection, etc.
Could you give us your opinions of Cyclosporine role in organ transplant ?
The basic immunosuppressive therapy was introduced in 80's of last century Cyclosporine has made a revolution, the success of organ transplantation!
Its action on the inhibition of T helper helper cells that do not secrete IL 2a proved to be very useful in the setting phase of rejection!
Thanks Distinguished Professor Coric for your interest and for successful cooperation!
I will answer Dr. Marini to another question, which will help me to repeat my answers, which I gave in my projects, and to take the coexisting races of the issues of the personality in the history of medicine, marked by its development of transplantation immunology!
Dr. Marini's answer to her third question about immunosuppressive therapy!
Answer dr.Marina on third question:
Dr. Marini's answer to her third question about immunosuppressive therapy
CLINICAL IMUNOSUPPRESSION
Since 1962, all tissue transplantation among non-related individuals has been performed on patients under the influence of chemical agents on the suppression of the immune response of the patient to the transplant. Many scientists have dealt with irradiation of the whole organism as a means of immunosuppression, irradiation of the entire transplant, and the use of drugs such as nitrogen mustard. The breakthrough was made when Schwartz and Dameshek from Tufts University worked on the action of 6-mercaptopurine on the xenogenic protein solution (12). They used a laboratory model in which the antigen was a serum albumin of a human or human being administered to a rat or hamster. By radioactive labeling of albumin, it was possible to follow the curve of its disappearance. Without immunosuppression, it could very well disappear from circulation, using circulating antibodies, but when animals were administered 6-mercaptopurine, the foreign protein had a normal disintegration time in the recipient's body fluid. Mr Roy Calne was then a young surgeon who worked postgraduate work in London. He applied the 6 mercaptopurine to the kidney - a transplant. During multidimensional observation, it was obvious that a completely new era in experimental renal transplantation began. Wanting to work on this and still to work with other researchers on this issue, Mr. Calne went to the United States. He worked with Murray and his group at the Peter Bent Brigham Hospital and at the Harvard Medical School. The mercaptopurine derivative, which was called Imuran (Azathioprine), was soon found. Results with Imuran were better than with mercaptopurine 6; Toxicity is smaller, and the longer duration of kidney transplantation in a dog becomes the rule. Among the first patients who were operated with immunosuppressive chemotherapy, he was a patient whose postoperative course, in April 1962, went without problems, and he lived for a long time (13). Between 1965 and 1975, kidney transplantation has largely entered into practice as a treatment for kidney disease.
Dr. Marini's answer to her third question about immunosuppressive therapy
CLINICAL IMUNOSUPPRESSION
. MONOCLONAL AND POLYCLONAL ANTIBODY
Monoclonal and polyclonal antibodies are used in treating the acute rejection of renal transplantation. The monoclonal antibody OKT3 and the polyclonal antibody-antilimphocytic globulin (ALG) were very effective in reversing the rejection of acute cadaver-transplan
Historical Perspectives on Relevance Immunology
transplant
It is generally accepted that the early work of scientists in the field of behavioral Medawar allo-transplant skin gene in laboratory rabbits, first published in the period 1944th-1946th, marked the formal beginning of modern transplantation period. The historical background of the time domain bears special relevance to our topic. Most of incentives to early research ventures in the field of transplant originated in the war-torn Great Britain in the 1940s, during the intensive efforts of the British and surgeons volunteers from other countries to treat and rehabilitate the pilots of Royal Air Force who were injured and mutilated during the legendary fighting for UK. One of the members of the volunteer surgical team, the late John Marquis Converse, worked closely with Sir. Harold Gillies employee in center for plastic surgery Park Prewett Hospital in Basingstoke, Hampshire.
During one of the many Converse's surgical operation, in the process of transplanting skin of a RAF pilot, Sir Harold is brought into the operating room, a tall, skinny, young zoologist from Oxford University and said, "Doctor Medawar is interested in the problem homograft. This declaration marked the beginning of a long friendship between Converse and Medawar, after talks in which the Medawar expressed special interest in the behavior of skin homograft and to process their rejection. During the discussion, it has been hypothesized that in case if the epidermis, which in itself has no blood vessels, could be separated from the vascular dermis, epidermis then it could survive as a free graft.
Converse gave a piece of skin Medawar, who returned to the lab and divide the epidermis from the dermis using raw-unsophisticated preparation Trypsin, which is in itself contained an enzyme elastase. The resulting leaf epidermis was placed on the patient granulation surface wounds, but he was gone by tomorrow.
This was Medawarovo first exposure to transpantiranju skin in humans, and this has led to its collaborative efforts with respected British plastic surgeon, Dr. Tom Gibson, with whom he Medawar published a classic study on human subjects. This experience has also marked the beginning of Medawarovog systematic experimental study of skin grafts rabbit, which has produced a basic foundation for the role of immunology in rejecting allografts. Converse enduring fascination with the field of transplantation is very intensified its work in Basingstoke-in. After his return to civilian life in 1948, he established one of the first America transplantation research laboratory at Bellevue Hospital in New York, and there was soon attracted a talented team of associates. (5)
Converse has early realized the need for frequent exchange of ideas between the then small society of doctors and biologists all over the world who have an interest in transplantation. Converse attended the conference, researcher in 1951, at a conference in Arden home, which was attended by the now legendary names as: TS Hauschka, D. M. Hume, N.Kaliss, C.C. Little, W. Longmire, R.E. Maumenee, PB Medawar and among others GD Snell. This meeting was initiated Conversa to seek ways and means to establish regular channels of exchange between the members of this new scientific discipline.
Converse has assured members of the Academy of Sciences of New York to sponsor a series "of International Conference on transplant" in order to provide the focal point for meetings in the various disciplines that were beginning to enter the field of transplantation. The first International Conference in the series, called "The attitude of Immunology at Homo tissue transplantation", held in New York in 1954. This name was not accidental; one of Conversovih most significant achievements during the year was the direct involvement of professional immunologists in transplantation.
Converse was convinced that the immunological approach was crucial to allow progress in our understanding allograftske reactivity.
Upon arrival at Bellevue Hospital in 1948, Converse has spent years trying to incorporate leading immunologists New York City, especially with the Rockefeller Institute of New York University, who had connections with the transplant. Unfortunately, during this period classical immunologists are looking to transplant with a touch of suspicion. Something in the spirit of a short memoir called "peripatetic school (Peripatetics) immune Surgeon," which was presented at the Fifth International Congress of the Association of transplantation, 1974:
"I remember well how we pray immunologists to attend to the early conferences. One immunologist visionary, Rueben L. Kahn, he finally agreed to come on the first Konferenciju- and scientific field called immunology is now a senior member of the club. The irony in all, in fact, that indicates that the transplant research then quickly sparked a renaissance-boom in the field of immunology orthodox ... "
The huge success of the conference on the "Attitudes Immunology with Homotransplantacijom Tissues" has begun to attract a growing number of prominent immunologist world-class on 6-th row transplant conference, sponsored by the New York-ery Academy of Sciences in the period 1956th-1966th Converse was chaired and organized by each of these meetings. He also collected the funds necessary to finance the costs of the conference and travel costs of experts. Issued "The conclusions of this conference," constitute a unique historical document, in which every modern principle of transplantation biology and medicine was presented and discussed, in a joint forum of general scientists and medical professionals (clinicians).
Exceptional is the fact that almost every central concept or hypothesis which supports our current efforts in the field of transplantation was first formulated in one of the above conferences. One early additional product of the First Conference of the New York Academy of Sciences, was the first successful kidney transplant, 10 months later (December 23, 1954), cond.
This event, as well as the pioneering research of kidney transplantation, scientists Hamburger and his group of scientists Hume's, Merrill and their colleagues, produced early evidence of clinical relevance transplantation, and as such, gave a strong impetus for further research. The resulting rapid growth in this field has stimulated the creation of the Transplantation Society during the final session of 7-Me International Transplantation Conference, New York-ery Academy of Sciences, 1966-year. As noted by Sir Michael's Woodruff, a 1975-this year, scientist John Marquis Converse was one of the true fathers osnivajućih the Transplantation Society. His influence, rather than the influence of any other scientist, has led to the creation of this society.
This event, as well as the pioneering research of kidney transplantation, scientists Hamburger and his group of scientists Hume's, Merrill and their colleagues, produced early evidence of clinical relevance transplantation, and as such, gave a strong impetus for further research. The resulting rapid growth in this field has stimulated the creation of the Transplantation Society during the final session of 7-Me International Transplantation Conference, New York-ery Academy of Sciences, 1966-year. As noted by Sir Michael's Woodruff, a 1975-this year, scientist John Marquis Converse was one of the true fathers osnivajućih the Transplantation Society. His influence, rather than the influence of any other scientist, has led to the creation of this society.
From its relatively modest beginnings, immunology has now assumed a fundamental role in the field of transplantation, and as such was responsible for accelerated progress to basic science and science at the clinical level. On the other hand, transplantation research has revolutionized orthodox Immunology. Such concepts as the resulting immune tolerance and the role of MHC in immune reactivity, for example, a direct result of cross-fertilization. Of particular importance at the present time would be to record this connection, when so many new disciplines, and especially molecular biology, entering the field of transplantation. It is safe to predict that each of these disciplines derive immense benefits from the challenges produced by transplantation.
One of the most relevant products relations immunology and transplantation was the discovery of the role of MHC (HLA in man), as the main qualifier immunoreactivity. History and development of HLA give a clear illustration of the extent of inter-disciplinary work and enthusiasm, who was such an integral part of the progress in the field of transplantation, from the birth of the modern era, 1944. We now propose to focus on the early beginnings and geometric explosion of knowledge that followed in the field, which is generally known as the "tissue typing a", as the prototype of involvement in immunology transplantation (7).
Can you please tell us about new desensitization methods in area of transplantation?
Thx in advance
It is the best for patient to spent to time, in observing his immune system from previous transplantation, according to the protocols that are being prepared for new organ transplantation!
To clarify the same procedure as in the earlier transplantation of the organs,for example a test of mix lymphocytes, a donor specific transfusion a plasmapheresis... etc!
Like IgG inactivating agents, anti-cytokine antibodies, costimulatory molecule blockers, complement inhibitors, and agents targeting plasma cells..
Thanks for answer.
Dear professor, thank you for your contribution in this demanding scientific field.
Thank you very much for successful cooperation ....
Best Regards
Jasenko Karamehic
5. ACTIVATION OF CYTOSOLIC ACCESSORIES
SIGNAL ROADS OF TIROZINE KINAZOM
Two key phosphorus changes alter the location and / or activity of two key proteins that initiate the main signaling cascades in T cells. PLC-γ1 and SHC. These proteins bind THC for two major pathways: release of intracellular calcium and activation of the RAS signal pathway.
PLC-γ1 is phosphorylated by TDR-associated tyrosine kinase and activated to hydrolyze membrane inositol phospholipid. The products of this hydrolysis are diacyl glycerol (DAG) and inositol triphosphate (IP3).