May 2000
Pigs are currently thought to be the best candidates for human organ donation and islets for diabetes treatment. Source: USDA
Introduction
Throughout human history there are periods when what was considered mere whimsy, the fruit of a fantastic imagination, becomes real. These situations challenge and change our ideas of what is normal and moral.
Right now we are being challenged by two technological innovations:
- Genetic engineering: this refers to the ability to take a gene from one source and introduce it to a new tissue or organ so that it will then express a new characteristic or feature.
- Xenotransplantation: this refers to the transplantation of an organ or tissue from a different (non-human) species into a human being.
The arrival of these technologies is ushering in new possibilities and new dilemmas. As for all human innovations, there will be no blanket answer, no moral cover-all that will help us decide what is acceptable. Rather we will have to wade our way through the messy details and decide case by case. As part of this process, this article will present a case for the use of these two technologies with specific reference to their potential to provide a cure for a presently incurable disease called Type I diabetes.
What is Type I diabetes?
Type I diabetes is a serious disease diagnosed mainly in children.
Type I diabetes affects approximately 1.5 million people in the United States.
The core issue of diabetes is an inability to control the level of glucose (sugar) in the blood.
Blood glucose levels are normally controlled by the hormone insulin, but the cells that make insulin are destroyed by the immune system in people with diabetes.
A lifetime of diabetes results in severe, debilitating consequences including kidney failure, adult blindness, nerve damage and blood vessel damage (leading to limb amputations, heart attack and stroke).
As a result of these complications diabetes sufferers have an average life expectancy 15 years less than that of non-diabetic people.
There is currently no available cure for diabetes that would prevent the occurrence of these consequences.
The search for a cure
Currently the only treatment option for the many diabetes sufferers is a daily injection of insulin. Unfortunately, this treatment is unable to prevent the occurrence of complications in the majority of diabetics. This sad reality has driven scientists to find alternate strategies that will cure diabetes.
In the early 1970’s it was demonstrated that islets of Langerhans (the tissue that produces insulin) isolated from one animal could be transplanted to another and cure diabetes. These were the first experiments demonstrating that transplantation might indeed offer a complete cure for diabetes.
This led to the initiation of an ambitious program to repeat this in humans. Thus, in the early 1980’s islets from cadaver organ donors were transplanted into diabetic patients.
However, despite the high optimism, the relative success of this procedure has been incredibly low. Of 270 islet transplants performed world wide by 1995, in only 5% (~14) of cases were the transplanted individuals still cured one year later. This is staggeringly low, especially when you consider that the success rates for other organ transplants are much higher (better than 90% for heart, lung and kidney transplants).
A more recent trial in Edmonton, Canada has met with higher success rates. However, in those cases it was necessary to provide each individual recipient with the equivalent of ‘two persons’ worth of islets. This is in contrast to the fact that we can survive quite well with as little as a third of our own islets.
The poor success of the earlier trials and the requirement for high numbers of islets in the latter is attributed to the rapid destruction and death of the islets following transplantation. The activation of an aggressive immune response against the newly transplanted islets is one factor involved in their death. Additionally, it is believed that transplanted islets are quite sensitive to their new environment, and in the time that it takes them to adjust to their new body, many of the islets die.
Apart from the issues surrounding islet survival there is an additional problem. Simply put there are not enough islets available.
- There are 1.5 million Type I diabetics in the US.
- The number of suitable islet donors in the US is less than 5000 per year.
- If we use two donors per person we could transplant 2,500 diabetics.
This amounts to less than 1% percent of the number of people who could benefit from such a therapy!
Solving the problems
Animals as spares?
Although it seemed conceptually easy to cure diabetes by transplanting new islets, in practice it has been far more difficult. The major hurdle is finding enough human islets to transplant all the people who could benefit from this treatment. The supply of islets from cadaver donors will never be sufficient to supply this need.
- One alternative is to take islets from living donors; however, this procedure has the risk of causing diabetes in the donor.
- Another possibility is to use fetal tissue to grow new islets, but currently this is not technically possible, aside from the ethical considerations concerning the use of human embryos.
- The issue of supply has led many researchers to discuss whether we could use islets from other animals to transplant into humans (xenotransplantation).
Although many different animal sources have been proposed, pig islets seem to be the most popular choice for two reasons:
- Physiological reasons — Pig insulin works well in humans (pig insulin is currently used for diabetes treatment). The blood levels of glucose in pigs and humans are similar.
- Practical reasons — The commercial rearing and breeding of pigs for food is currently practiced. This knowledge could be used to develop facilities for large-scale preparation of pig islets.
However, there are still many important issues that need to be addressed before pig islets can be used in humans. One basic issue is to decide whether it is ethically acceptable to use animals as a source of ‘parts’ for humans. If it is agreed that this is acceptable, the use of pigs may be more justifiable than the use of non-human primates for the reason that pigs are currently utilized as a food source. Other issues are more technical but no less important. For instance, there has been a vigorous debate as to whether the use of pig tissues may expose the human population to dangerous new viruses. This issue must be resolved before we can consider widespread transplantation of pig tissues into humans.
Genetic engineering
The use of pigs may provide an excellent source of islets for the treatment of diabetes by transplantation. However, such an approach would still require that we overcome the problems of islet survival following transplantation. The use of pig islets for instance, would not deter the immune system. The current strategy in most transplant situations is to suppress the immune system with powerful inhibitory drugs known as immunosuppressants. However, these drugs are not as effective at preventing immune attack on the islets in people with diabetes. More importantly their use in islet transplantation is considered ethically unacceptable. This due to the fact that they have many toxic effects and their long term use may cause developmental problems in children. Given the fact that these drugs will have to be taken for the whole life of the transplant recipient and that most Type I diabetics are children these are important considerations. This dilemma has again led to a search for new answers, of which genetic engineering of islets is one option.
Genetic engineering in this sense refers to the technology by which we can artificially add a gene to a tissue so that it will then express a new characteristic or feature.
For diabetes, this might mean using a genetic engineering approach to make a ‘super’ islet that cannot be destroyed. This idea has been spurred on by research showing that normal cells in our bodies can protect themselves from dying, or being killed by the immune system, by making specialized protective proteins. It is suggested that if we genetically engineer islets to express these proteins they might then survive in the absence of any other treatment.
Genetic engineering also offers the promise of other treatments that do not involve transplants at all. One is to just add back a new copy of the gene that codes for insulin production. Nevertheless, this also suffers from many difficulties. Were will we put the gene? How can we engineer the insulin gene so that it will produce insulin in the right amounts? These are not trivial problems but in December of 2000, a group from Korea demonstrated that this could, in fact, cure diabetes in an animal using this approach.
Conclusion
Type I diabetes is a serious debilitating disease with no effective cure. The arrival of new technologies such as xenotransplantation and genetic engineering has created a hope in the diabetes community that they can bring the promise of a cure. But they also bring new dilemmas. How will we finally decide?
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