The Xenotransplantation Ethics Debate
In theory, xenotransplantation could be viewed as a life-saving answer for many awaiting organ transplants, and for doctors dealing with organ shortages. However, the use of animal organs for human transplants has been under scrutiny since the inception of the idea, due to the many risks involved, not only to the patient but the general public, and bioethics issues pertaining to the use of animals for human advancement.
Several years ago it appeared the main roadblock to using pig organs for xenotransplantation was the presence of galactosyl (GAL) moieties linked to the cell surfaces of animal tissues and produced by the enzyme alpha-galactosyl transferase. Primates, including humans, do not have GAL-linkages on their cell surfaces and produce antibodies against them, causing the rejection of transplanted animal organs.
It has since been established that the causes for organ rejection are more complicated than that, and additional antigens have been implicated in the human immune system response. However, immunological issues remain the main roadblocks to xenotransplantation, according to Dr. Muhammad Mohiuddin of the NIH Cardiothoracic Surgery Research Program, National Heart, Lung, and Blood Institute.
In addition to the immunological issues, there are safety concerns for whole populations, due to the possibility of infection of an organ recipient by an animal virus, and animal rights issues, that result in ethical debate over the topic of xenotransplantation. As a result, there are also many regulatory hurdles to overcome, before xenotransplantation becomes everyday practice.
What's at Stake?
Transplants of animal organs to humans is obviously performed at the expense of the animal in question. Animal rights advocates believe that it is not morally acceptable to sacrifice animals for the benefit of human lives, whether for the use of their organs or for research necessary to study the immunological factors causing organ rejection.
Humans are not without risk in this issue either. The effects latent animal viruses will have on human organ recipients are still unknown. Opponents of xenotransplantation fear that these viruses, when introduced into a human system might cause epidemics of diseases for which we have no immunity and no cure. Pigs, for example, currently the best candidate animal species for culturing organs for humans, carry a retrovirus called PERV (Porcine Endogenous Retrovirus). This virus has been shown to infect human cells and the consequences of infection have not yet been determined.
Some opponents of xenotransplantation believe that animals are not the solution, but that biotech companies are just looking to make money from their ability to clone animal cells and create GMOs, specifically GM pigs (knockouts lacking the alpha-galactosyl transferase enzyme).
Using animal organs would reduce the length of time many people have to wait for a suitable organ, and would allow transplants to occur while the recipient is still strong and somewhat healthy and better able to tolerate surgery. According to statistics quoted by the Lincoln Journal Star, the current number of 20,000 transplants per year in America could be increased to over 100,000, if animal organs were used, and 12 out of 73,000 Americans waiting for transplants die each day.
It is hoped that current practices of injecting donor cells into pig embryos, in utero, will eliminate the need for immunosuppressant drugs as this has been shown to make the donor and recipient compatible when tested on pigs and other animals. This means using molecular genetics techniques to create GM animals, specifically altered to be a match for an individual human recipient. The knockout species would be conceived and raised for the sole purpose of being sacrificed for medicine.
Pigs are a good choice of organ donor because of their short gestation period, rapid growth rate and size of organs (matching those of humans). Hyperacute rejection (HAR) of organs from Gal-knockout pigs transplanted into baboons was prevented due to the absence of expression of the 1,3-galactosyltransferase gene. Although other immune responses are present, there is hope that similar genetic alterations will be possible, to address the issue of HAR in humans.
According to Dr. Muhammad Mohiuddin, ethical issues based on the possibility of a disease spread from animals to humans seem to hold less water than previously thought, since PERV has not been found to infect any humans treated with pig tissues to date, nor have any epidemics arisen from infection of human farm workers involved in handling pigs.
Pigs are very clean and can be raised in exceptionally clean environments if necessary. Pig farms for research on xenotransplantation contain barns fitted with filters for keeping out viruses and bacteria. In future, if/when the pigs are raised for human transplants, even farm workers will wear masks to prevent exposure of the pigs to human pathogens.
Ethical issues surrounding the use of animal organs for human transplants appear to be threefold. There is the issue of animal rights and the breeding of animals simply for human consumption and medical benefit. Secondly, there are some who believe that xenotransplant technology is just another way for biotech companies to make money, and they are not concerned with the welfare of the animals or truly concerned with the welfare of mankind, due to their perceived disregard for the third issue, which is the unknown impact on the human race, should a new infection be introduced for which we have no cure.
Where It Stands
Experts involved in xenotransplant research seem to dismiss many of the arguments against the technology. According to lead researcher Dr. William Beschorner at the University of Nebraska Medical Center, who has successfully transplanted hearts and major blood vessels between pigs and sheep, the class action and malpractice lawsuits that could arise from foolishly jumping the gun, before all the risks have been addressed, should be enough to deter anyone from risking the safety of consumers just to make money.
Furthermore, one anonymous farmer was quoted by Bob Reeves of the Lincoln Journal Star as saying the profits to pig farmers would be minuscule.
Ethicist Dr. Andrew Jameton, from the Nebraska Medical Center in Omaha, pointed out that this issue is no different from research in any medical field. Although the desire for recognition and compensation for the cost of research is always a temptation, especailly where venture capitalists are involved, "scientists in all fields must guard against letting profit get ahead of scientific method and accuracy". That is, the issue of integrity is no greater in this than in any other field of science and should not necessarily be viewed as a reason to hold back the technology to save lives.
Scientists involved in xenotransplant research say their research is highly regulated and that the animals involved are treated with the greatest respect, in addition to being given any painkillers or anesthetics required to make them comfortable. In many experiments, nerve cells are not connected to transplanted organs, so the animals cannot feel pain from the organ being rejected.
Realistically, it must be acknowledged that none of the medical advances of mankind could have been accomplished without animal experimentation. However, the fact remains that xenotransplantation is ethically on a whole different level, as even after the technology is established, animals lives will continuously need to be sacrificed for the lives of human beneficiaries.
Mohiuddin, M. Clinical Xenotransplantation of Organs: Why aren’t we there yet? PLOS Med. 4(3):e75. doi:10.1371/journal.pmed.0040075.
Reeves, B. Animal Organs Hold Promise for Humans, Designer Pigs Goal of Med Center Research, and Special Farm Supports Research. Lincoln Journal Star online series on Medical Ethics: Tough Choices.