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Biology 103
2001 Second Web Report
On Serendip

Xenotransplantation

H.A.

With approximately 48,000 individuals on the waiting list for organ transplants and only about 4,835 people donating their organs after death each year, there are around 3,000 yearly deaths for those who do not have these organs available to the them (1). Consequently, medicine has turned to an additional yet somewhat controversial source for organ donations: animals. The term xenotransplantation is defined as "the transplantation of living organs, cells or tissue from one species to another..." (2). The obvious and primary benefit of such a procedure is increasing the number of new leases on life that medicine can issue to the thousands waiting for organ transplants. Nevertheless, a variety of ethical issues are raised by such practices, ranging from the treatment of animals to the effects of xenotransplantation in crossing the species border.

Xenotransplantation is by no means a new concept in medicine. Combining parts of different species dates back to Greek lore of over 3,000 years ago in the forms of centaurs (half man and half horse) and the Chimera (a mixture of goat, lion and serpent). In terms of medical procedures, the earliest example of combining man and animal parts was in 1682, when a Russian physician repaired a man's skull using the bone of a dog. After the turn of the 20th century, doctors began grafting tissues from animals to humans, a prime example of this being in 1905, when a French surgeon used slices of rabbit kidney to treat a child suffering from kidney failure. As exploration into xenotransplantation continued with other animals such as pigs, goats, lambs and monkeys, doctors began to notice that these transplants would fail in relatively short amounts of time, lasting for only weeks at best. It wasn't until the 1940's, when the cause for these transplantation failures, and thus the most significant setback within xenotransplantation, was identified as a crucial connection between the immune system and the rejection of a transplanted organ (3).

Two of the most crucial risks involved with xenotransplantation are rejection and xenozoonoses. Rejection primarily involves how the immune system uses several lines of defense against infection from foreign organisms like parasites and bacteria, and specifically when the system attacks transplants. "These defense mechanisms are a double-edged sword...in xenotransplantation, we are walking a fine line between asking the immune system to accept an organ from an animal, but still protect us from other threats, such as infectious disease" (4). To combat this, doctors have been trying various methods of modifying xenotransplantation procedures. One way is to attempt to alter the recipient's immune system to increase transplant tolerance. Another is to utilize genetic engineering to change the organs, cells, and tissues of the donating animal, especially by deleting certain animal genes to be replaced by human genes (2). An example of this transgenic procedure was in 1992, when doctors introduced a human gene that directs the production of a human complement-inhibiting protein into pig embryos, in order to prevent human complement proteins from doing damage (3). While experiments such as these have yet to solve the problem of rejection, the goal is becoming less and less elusive as medicine increases its options for "tricking" the immune system.

The concern of xenozoonoses is centered upon the delicate issue of animal viruses crossing the species barrier and causing human disease, and is also a good place to begin the ethics discussion of xenotransplantation. Not only does it raise questions about the safety of using animal organs in individuals, but it can potentially place the rest of society at great risk as well. The fact that putting living organs into the human body allows pathogens (organisms that cause disease) to bypass natural barriers like skin and the gastrointestinal tract, in addition to the reality that it is difficult to screen animals for these pathogens when we may not even know what they are, makes the spread of deadly infection quite possible (2). While many believe this was the starting point for how AIDS spread through the human race, it is no wonder that the ethical debate over this aspect is concerned with whether or not we have the right to risk the health of so many people by pursuing a procedure that involves significant dangers which we know relatively little about.

Breaking away from such a physical and biological basis, the risks of xenotransplantation extend into more philosophical issues of ethics. At the forefront of these is the use of animals as organ donors. Experts ask, "...is it inherently wrong to use animals for xenotransplantation or to treat them in a the way that is necessary to make them suitable as organ donors?" With relation to the use of animals in itself, doctors also need to know the best species of animal for transplantation use. The general debate has shown that, even though primates are genetically closest to humans, there are other factors such as the endangerment of many species, and perhaps most importantly, the idea that "the likelihood of the transfer of infective agents [is] more likely between more closely related species..." (5). Consequently, the transplant animal of choice has become the pig since their organs are most comparable in size to adult human recipients', they have large litters, grow quickly to maturity, and can be raised in sterile environments (2).

Finally, a major ethical issue has been the human-animal interface inherent in xenotransplantation. Various viewpoints regarding whether or not humans have a particular station and position among living organisms cause some complication with the principles of the transfer of human genes into animals as well as animal organs into human bodies. Experts on xenotransplantation issues say the questions revolve around not only "...the physical realities they [mixings] create, but also with respect to important societal values and, in particular, with respect to maintaining respect for both human and animal life" (5). Perhaps answering these questions may have to wait until the risks of xenotransplantation are better defined and stronger security measures can be identified.

In essence, xenotransplantation is like so many advances in the world of medicine: the advantage would be greatly significant and helpful to humans, yet the risks involved are many, the dangers are not completely defined, and the community questions whether or not medicine is prepared to make such potentialities a reality. There is also the complexity that risks such as contracting foreign disease would not only be exclusive to those who may agree to taking them, but may affect thousands of innocent people. While there are no blueprints for handling new advances in medicine, one of the required stages is to first become aware of as much information as possible surrounding the steps in consideration. Following this, formalizing a "worst-case" scenario could help doctors decide whether the risks are worth it. Granted, there will most likely never be perfect unanimity between doctors, experts, society, etc., but the taking of risks has been the key to advancement throughout history. At this point, an educated decision is the best society can hope for.

WWW Sources

1)FDA Fact Sheet on Xenotransplantation, government site that covers the basics of xenotransplantation

2)ABC's of Xeno ,Canadian site with comprehensive discussion of xenotransplantation concepts, including definition, risks analysis, legal considerations, etc.

3)Xenotransplantation ,Scientific American article about the historical, current, and future implications of xenotransplantation

4) Xenotransplantation: Animal Organs to Save Human Lives,Duke University site covering transplant rejection situations

5) A Retrospective Overview of the Discussion of the Ethical Issues , closing remarks of Dr. Margaret A. Sommerville from Health Canada's National Forum on Xenotransplantation discussing ethical issues




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