Ethics and the clinical utility of animal organs Katrina A. Bramstedt enotransplantation (cross-species transplantation) seems to be clearly on the medical horizon, yet the mere thought of the term can make some cringe while giving others a smile of hope. Why can one find these two diametrically opposed reactions to the same thought? Are there justifiable reasons for an ethical distinction between using whole animal organs for transplantation and the harvesting of cells and proteins from animal organs for clinical use? Should medicine’s focus be the development of artificial devices and cloned human organs instead of xenotransplants? In the USA, emotional uproar may have put most xenotransplantation research under wraps but research of this nature has not abated. Because of this, the ethical questions posed by this technology must be contemplated beforehand. Some might argue that the death of animals used for clinical medicine violates animal rights and thus makes this technology unethical, but I argue that death is implicit in many non-medicinal uses of animals (e.g. as a food source), making the organ’s destination ethically insignificant.
Polling A recent study published in The Lancet indicated that, of 113 Australian renal-failure patients surveyed, only 48% believed it appropriate to breed animals to provide organs for human transplantation and only 42% were willing to accept an animal organ for their transplant1. There was no difference in the acceptance rate for organs that were from species that were closely or distantly related to humans. Another study surveyed British renal-failure patients, with results indicating that 78% were willing to accept a pig kidney for their transplant. This group of patients indicated that they saw no moral distinction between pigs bred for human food and pigs bred specifically for saving lives2. Zoonosis and rejection risks aside, these studies highlight the fact that there is a wide range of ethical opinion regarding the technology of whole-organ xenotransplantation. Interestingly, the reasons for viewing it as ethically impermissible often do not seem to relate to the general clinical use of animal tissue but rather to the use of whole organs for transplant. I make this statement to pose the following argument: looking at their structural and functional relationships, there is no justifiable ethical distinction between animal-tissue (and animalcell) transplants and whole-animal-organ transplants. Biology schematic Whole-organ xenotransplantation can be argued to be ethically permissible either as a bridging technology (temporary in vivo or ex vivo transplant) or as a permanent replacement using the biological model of structure. The biological scheme of life is organized as follows: molecules→cells→tissues→organs→organisms. K. A. Bramstedt ([email protected]
) is in the Biomedical and Research Ethics Program at the University of California Los Angeles, CHS 52-242, Los Angeles, CA 90095-7041, USA.
Currently, animal molecules, cells and tissues are used for human patient therapy; for example, bovine insulin and porcine heart valves. In a recent study, foetal pig cells were implanted into the brains of two epilepsy patients3. No side effects were observed and both patients experienced a reduction in their seizure episodes. Extracted cells can also be used for incorporation into medical devices such as the Encellin XP device, which uses porcine islets of Langerhans embedded in a hydrogel matrix and is implanted to give responsive insulin production (http://www.islet.org/ 18.htm). Because organs are tissues integrated to perform a specific function, there can be no ethical distinction between allowing animal-tissue (and animal-cell) transplants and allowing whole-animal-organ transplantation. Even though the organs are much more structurally detailed, they are nonetheless intrinsically related to cells and tissue. Furthermore, it is the unique, integrated relationship of all four organizational components that makes drawing the line (ethically speaking) at whole-organ xenotransplants arbitrary. Organ harvesting Some are opposed to whole-organ xenotransplantation because they believe it results in the killing of an animal for the harvesting of one organ, with the remainder of the animal discarded. Those who work in either academic or commercial biotechnology know that this, in fact, does not have to be the case. Analysing the concept more deeply, one finds that, although the animal may die owing to its organ being removed, the removal of that organ alone is not necessarily the complete picture. In addition to retrieval of the organ destined for potential transplant, tissues, cells and other organs can be retrieved for protein and enzyme extraction. Other organ subparts could also be used for transplant (e.g. heart valves), so a large majority of the animal can be effectively used for medical purposes. Indeed, it can be argued that using animals for the extraction of enzymes and proteins without including the removal of whole organs for transplant is also potentially wasteful of medical resources. Meal or medicine? Clothing or cure? The quantity of animals that would be used to satisfy the organ-pool deficiency (if technologically achievable) is very small compared with the billions of animals slaughtered for food – it would take only 100 breeding sows to meet the entire UK kidney shortfall4. It would seem that slaughtering a sow to donate organs to a transplant pool would surely be at least as justified as if she were slaughtered for a platter of bacon. Furthermore, it would seem that it cannot be more ethical to use animal tissue to satisfy human hunger pangs than to use animal tissue to save human life via a transplant. In both instances, the tissue is used as nourishment to a human body. There seems to be no justification in terming one form of nourishment ethically
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TIBTECH NOVEMBER 1999 (VOL 17)
FEATURE permissible and the other ethically impermissible. Try defining an ethical distinction to the liver-disease patient who was kept alive using five pig livers via ex vivo perfusion until a human liver became available for transplantation5. Death is implicit in all forms of animal usage discussed above, including the use of animal tissue for clothing, shoes and baseball gloves, making the destination ethically insignificant. Admittedly, there will be those who will argue that using animals for food or medicinals is unethical under all circumstances. Regarding transplantation, some might argue that medicine’s focus should be on the development of human-organ cloning and artificial replacement organs instead of xenotransplants. Both artificial organs and xenotransplants present physiological rejection issues but there may be foreseeable instances in which one method is preferred over the other (e.g. optimal organ size, organ availability). Furthermore, there may be
clinical instances in which an artificial replacement organ would never be feasible and a whole-organ xenotransplant is the only solution. Although the in vitro production of whole human organs from human cells may avoid the need for immunosuppression, this technology has yet to be successful, and it may be more expensive than the use of more readily available animal organs. These reasons, along with the seemingly permanent shortage of donated human organs, provide justification to continue developing xenotransplant technology in the hope of perfecting it for human use. References 1 2 3 4 5
Mohacsi, P. J. et al. (1997) Lancet 349, 1031 Ward, E. (1997) Lancet 349, 1775 Schachter, S. C. et al. (1998) Epilepsia 39 (Suppl.), 67 Abdulla, S. (1997) Lancet 350, 868 Chari, R. S. et al. (1994) New Engl. J. Med. 331, 234–237
Knowledge discovery in gene-expressionmicroarray data: mining the information output of the genome Gary Zweiger A key aspect of the genomics revolution is the transformation of large amounts of biological information into an electronic format, leading to an information-based approach to biomedical problems. Large-scale RNA assays and gene-expressionmicroarray studies, in particular, represent the second wave of the genomics revolution, providing gene-expression data that complement gene-sequence data and help our understanding of the molecular basis of health and disease. They are being applied at several stages in the drug-development process and could ultimately have broad applications in disease diagnosis and patient prognosis.
or the biomedical sciences, the 20th century has been the century of the gene. Mendel’s ‘factors’ were rediscovered in 1900 and, over the course of the century, became increasingly relied upon to explain biological phenomena, to create diagnostic tests and to develop new disease treatments. Genes are now defined by their DNA sequences, as this information determines RNA and protein structures, which underlie the function and dysfunction of biological processes. Gene sequences relate each gene to a set of ancestral genes. Expressed sequence tags (ESTs) and other highthroughput sequencing schemes, coupled with new bioinformatics techniques and the collective findings from decades of molecular studies, have enabled a large number of gene sequences to be identified, related to other gene sequences and functionally annotated1,2. Our
G. Zweiger ([email protected]
) is at Incyte Pharmaceuticals, 3174 Porter Drive, Palo Alto, CA 94304, USA. TIBTECH NOVEMBER 1999 (VOL 17)
knowledge of this web of gene relationships has grown enormously and has been instrumental to many other advances in the biomedical sciences. This tremendous knowledge base enables DNA sequences (from a crime scene, ancient remains or a newly discovered gene) to have immediate and great utility. Such is the legacy of the first wave of the genomics revolution. The value of gene coding sequences and the resulting molecular structures and biochemical properties is indisputably great. However, organisms need additional information to operate. For us to understand the molecular basis of health and disease, we need to know more than coding sequences, molecular structures and biochemical actions. We need to know which gene products are made, how much is made and where, when and under what circumstances it is made; that is, we need to understand gene expression. Although the discovery of disease-causing genes and proteins, such as BRCA1 (Ref. 3), BRCA2 (Ref. 4),
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