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History Of Organ Transplantation
First successful living-related kidney Transplant
First successful cadaveric (deceased) kidney transplant
First successful lung transplant
First successful liver transplant
First Successful Heart Transplant
Uniform Anatomical Gift Act – Establishes Uniform Donor Card as a legal document for anyone 18 years of age or older to legally donate his or her organs upon death
End Stage Renal Disease Act (ESRD) paves way for Medicare Coverage of Renal Dialysis and Kidney Transplants
First Successful heart/lung Transplant
FDA approves Cyclosporine, the most successful anti-rejection medication developed to date
National Organ Transplant Act (NOTA) establishes nationwide computer registry operated by the United Network for Organ Sharing (UNOS); authorizes financial support for Organ Procurement Organizations (OPOs); prohibits buying or selling of organs in the United States
Required Request Laws require hospitals to develop policies to identify patients as potential donors and approach families about organ donation
FDA approves Viaspan that greatly extends the preservation of donated livers
First successful small intestine transplant
First successful living-related liver transplant
First successful living-related lung transplant
Baboon liver transplanted into man dying of liver failure
National Conditions of Participation legislation enacted; required hospitals to refer all deaths, and imminent deaths, to the local Organ Procurement Organizations (OPOs)
Donated corneas (the clear part on the front of the eye) can restore sight for individuals who cannot see because of damage to their corneas. In addition, the sclera of the eye (the white part) is sometimes used in glaucoma surgeries or to repair trauma to the eye.
The kidneys extract waste from the blood and produces important hormones. Kidney transplants are the second most common transplant operation, following cornea transplants. Over 12,000 kidney transplants were performed in the U.S in 1999. Kidney transplants can save the lives of individuals with kidney disease or kidney failure, which may be caused by severe, uncontrolled high blood pressure, by a variety of infections, or by diabetes mellitus. Successful kidney transplants restore the body’s ability to remove waste, as well as to regulate blood pressure, blood volume, and the chemical (electrolyte) composition of the blood. Healthy kidneys from either living donors (usually blood relatives) or from recently deceased donors may be used for a transplant. With the use of drugs to prevent rejection of the organ, between 80 and 90% of transplanted kidneys are functioning two years after the surgery.
Definition of Autograft
Autograft: Tissue transplanted from one part of the body to another in the same individual. Also called an autotransplant.
Definition of Allograft
Allograft: The transplant of an organ or tissue from one individual to another of the same species with a different genotype. A transplant from one person to another, but not an identical twin, is an allograft. Allografts account for many human transplants, including those from cadaveric, living related, and living unrelated donors. Called also an allogeneic graft or a homograft.
Definition of Immunosuppression
Immunosuppression: Suppression of the immune system. Immunosuppression may result from certain diseases such as AIDS or lymphoma or from certain drugs such as some of those used to treat cancer. Immunosuppression may also be deliberately induced with drugs, as in preparation for bone marrow or other organ transplantation to prevent the rejection of the transplant.
Animal to human transplant. Animals used as organ and tissue sources include pigs and primates. Transplants carried out (with varying degrees of success) include heart, kidney, liver, bone marrow, fetal neural tissue (to treat Parkinson's disease), and fetal islet tissue (for diabetes). The first xenotransplants took place in 1964 (pig heart valves in the UK; chimpanzee kidneys in the USA).
The idea of transplanting organs is not new. It can be found in myths of the ancient Greeks and was referred to by even older civilizations. But until the middle of the twentieth century it remained largely impossible, a piece of myth, or fantasy, or science fiction. Skin and eyes were among the first successful transplants. But the larger, more complex, and imbedded organs posed countless problems. The kidney was the first such organ to be successfully transplanted.
Since humans naturally have two kidneys, but can live with just one, the kidney lent itself well to the process. (Of the major organs, the kidney is still the one most often transplanted.) The first attempts in the early 1950s, as in all transplant cases, were made when the only other alternative for the patient was death. These early patients briefly raised hopes by starting a good recovery, but then succumbed. The future of transplant surgery began to look very bleak.
Meanwhile, Peter Medawar in Great Britain had been researching the topic of rejection, which he had observed in skin grafts as a wartime surgeon. He found that graft recipients would form antibodies against the graft, unless they had been exposed to similar foreign tissue early in life. (He used chickens for his research subjects.) Medawar's work showed that the body's rejection of foreign tissue was indeed an immune response. He and another researcher received the 1960 Nobel Prize for this discovery.
But in 1954 at the Peter Bent Brigham Hospital in Boston, a special kidney transpant case would succeed and teach medicine a great deal by confirming Medawar's results. Richard and Ronald Herrick were identical twins, but Richard was dying of kidney disease. Ronald donated one of his kidneys, and it was successfully transplanted into Richard. Because they were identical twins, the organ did not appear foreign to Richard's body, which did not reject it.
There were ethical problems in this new procedure that bothered some doctors: To cure one patient, they had to harm another healthy person (by taking out a kidney). But this was the least of their stumbling blocks. How could they trick the body into not rejecting the new, healthy kidney that it needed? X-rays were tried, bombarding the patient's entire body. The immune system was indeed knocked out, but in many cases the radiation killed the patient. In 1959, two more doctors in Boston discovered that certain drugs could suppress the immune system as effectively as radiation, but without the side effects of x-rays. One of these drugs was Imuran, originally formulated to fight leukemia. In addition, in 1960, Peter Medawar introduced a way of typing tissue, just as blood typing had been discovered in 1900. By 1962, tissue typing and immune suppression with drugs was used for the first time in a human kidney transplant. Between 1954 and 1973, about 10,000 kideny transplants were performed.
A more effective immunosuppressant, cyclosporine, has been discovered. Cyclosporine, generally introduced in the 1980s, was a breakthrough in preventing rejection and opened a new era in transplant surgery. In 1986 alone, for example, nearly 9,000 kidney transplants were performed in the United States, with a greater than 85 percent survival rate for the first year.
there are not enough donors to help everyone that needs a transplant.
the number of people receiving transplants is a lot but nowhere near enough to provide everyone with a transplant that needs one
There are about 6x the amount of people needing transplants than there are donors
FRAME has serious concerns about the use of animals as transplant donors for humans (xenotransplantation) because of the conditions in which donor animals would need to be housed and the potential harm to the animal of carrying the necessary parts of the human genetic code that make xenotransplantation possible. FRAME supports a reassessment of the current donor system to find ways to maximise the number of available human organs. It also wants to see increased funding for development of alternatives such as tissue engineering and mechanical solutions.Pigs and baboons are the most likely animals to be used for xenotransplantation. It is considered that the use of pigs is more ethically acceptable since society kills pigs for meat and therefore should be consistent in allowing their use for medical purposes. There are even some indications that pigs used for xenotransplantation will be better cared for than those reared for meat. Xenotransplantation will increase the number of animals used for biomedical purposes. It is not known how long an animal organ can survive in the human body, and it is proposed that animal organs will be used as mere "stop gaps" until a suitable human donor is found. If the animal organ is removed from the patient after only a few weeks because a suitable human donor is found, the issue of whether the animal organ can be used for another individual has to be resolved. It remains to be established whether the use of each animal could be maximised by moer than one organ being removed at the same time. However, sequential removal of tissues or organs should be prohibited on the grounds that it would cause undue suffering to the donor animals. Animal donors would have to live in pathogen-free conditions, in order to prevent infection that might compromise the organs. Keeping the animals in such conditions could cause distress and affect the physical well-being of the animals concerned. Consequently, the physiological and psychological well-being of the donor animals should be assessed by trained specialists. The effects of introducing the human decay accelerating factor (DAF) protein into the donor animal must be established. The welfare of animals that carry the human DAF gene should be assessed and compared to non-transgenic animals. It is possible that if the donor animal's immune system does not recognise the human DAF protein that this could cause a reduction in the efficiency of the immune system as a whole and an increase in the susceptibility of these animals to infection. The organ donor system as a whole should be re-assessed in order to find ways of maximising the number of human donors available. Perhaps the UK should introduce an 'opt-out' system to replace the current 'opt-in' system. There should be funding provided for the development of alternatives (e.g. tissue engineering and mechanical hearts) and for improving disease prevention. Non-human primates should not be used as donors, for ethical reasons, especially as the organs may only be in place for a short time, and in view of the potential for disease transmission. A welfare assessment of potential donor pigs for xenotransplantation should be conducted and a scheme for operating the cost/benefit analysis produced. The welfare of animals bred for xenotransplantation must be constantly monitored and not compromised for commercial reasons. See the Nuffield report for further information on this topic.
he transplantation of animal organs into humans - xenotransplantation – has been under discussion for several years as a future supplement or even alternative to human organ donation. Besides the understandable (although not uncontested) hopes, there have been plausible warnings of real and possibly difficult-to-control risks of infection to patients, their environment and ultimately the entire population. This contradictory and tense situation and the still largely unresolved potential of xenotransplantation require a sober review of the position and unbiased assessment at all levels of society.
The present report on a commission by the Committee for Education, Research and Technology Assessment provides an overview of the international discussion and, above all, of the (research and health) policy debate on the prospects for and challenges of xenotransplantation, essays a review of the current state of scientific and medical research, outlines the legal situation in Germany and central ethical issues and uses this as a basis to draw up suggestions for further scientific, political and social debate and need for action. The report deals with xenotransplantation of discrete organs, but not of tissues or cells.
The international debate
The growing interest in the potential and problems of this new medical technology is reflected in a growing number of expert reports, opinions and other documents on xenotransplantation commissioned by governments, national agencies or international organisations. Section II summarises the results of a comparative analysis of selected publications. Overall, the analysis shows growing scepticism regarding the hope that xenotransplantation can be developed in the foreseeable future into a low-risk therapeutic approach. Another striking feature is the almost unanimous call for guidelines for binding regulations to govern the launch of clinical trials and limit their potential risks.
Medical and scientific aspects
The state of RD on xenotransplantation (section III) can be described in terms of three key issues: overcoming rejection, ensuring physiological functionality and mastering the risks of infection. Even in human organ transplants, rejection of foreign organs by the recipient immune system is still the biggest problem, and implanting an animal organ into a human additionally involves defensive reactions which are not only more severe but also entirely different in nature (section III.1). Of these, only the so-called hyperacute rejection seems to be controllable to some extent, primarily through advances in producing genetically modified pigs (pig organs). There is still immense need for research on the three other phases of rejection (acute vascular/delayed, cellular and chronic). The same is true of the question of physiological tolerance and functionality of the organs (section III.2), which has hardly been studied at all or has been impossible to study. Meanwhile, however, the most important issue in the debate is the substantial risk of infection (section III.3) by so far unknown probabloy viral pathogens, which would not only affect the recipient but also be a potential threat reaching far beyond their immediate surroundings. Here again, research is still in its infancy. Nevertheless, it is likely that clinical trials will start in only a few years. The time horizon for further dissemination of xenotransplantation is likely to be at least 15-20 years (section III.4).
A comparison with alternative technologies (artificial or bioartificial organs, therapy for the relevant diseases) also shows that these also are long-term options whose advantages and disadvantages should be thoroughly examined.
The review of the international state of research (section III.5) shows that Germany is one of the leading locations for research in the field of xenotransplantation, alongside the dominant USA and UK.
Law and ethics
The unresolved risks of infection in particular have led to the almost unanimous view – even internationally speaking – that xenotransplantation needs special regulation, at least nationally, but basically internationally. Several countries have launched initiatives in this area or have already even created institutions. An overview of the legal situation in Germany (section IV) shows that while e.g. the legislation on drugs, genetic engineering and animal protection is relevant to xenotransplantation in the area covered (although not the Transplantation Act), there is reason to doubt that existing standards adequately deal with the significance of this medical neotechnology with consequences which are potential global in their dimensions. The identifiable need for research and action here leads to the call for careful legal debate and review of legal policy by the relevant bodies.
The ethical debate (section V) shows two main emphases: consideration of moral rights and interests of humans and exploration of the possible conflict between human and animal rights and interests. The human ethical aspects of xenotransplantation (section V.1) are particularly diverse, and mostly very closely interrelated. Issues intensively discussed include e.g. reducing the shortage of transplantable organs, improving the equity in distribution, the ethics of human experiments, the current lack of any sign of an ability to deal with the infection risk, informed agreement and medical and social alternatives. The ethics of species and nature, and particularly the ethics of animals show clearly that the rights and interests of animals as "moral beings" are considerably endangered (section V.2). An ethical justification of xenotransplantation can accordingly only be achieved through carefully based and viable arguments. Ultimately, these are needed to answer the question whether human suffering has sufficient priority to justify acceptance of the sufferings and death of animals. Summarising the ethical debate, we can say that the ethical debate over whether xenotransplantation is justified is currently dominated by scepticism.
Need for discussion and action
The issue of xenotransplantation can be seen as needing extensive debate and action not least by virtue of the contradictions and problems that it raises (section VI):
- The academic community is called upon urgently to review and evaluate the state of R&D in a way which integrates overall the technological and professional aspects.
- Politics is called upon to follow the example of other states and the recommendation of virtually all relevant expert opinions to draft and implement an appropriate regulatory strategy for xenotransplantation.
- Society as a whole is called upon to consider ethically the possible benefits of and damage arising from xenotransplantation and to develop socially tolerable (or at least acceptable) solutions for the problems facing us.
Corresponding activities would be particularly desirable as a way of linking the debate in Germany with the significantly more advanced state of discussion elsewhere.
This student written piece of work is one of many that can be found in our GCSE Humans as Organisms section.
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