Xenotransplantation - Nuffield Council on Bioethics

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Animal-to-Human Transplants : the ethics of xenotransplantation emerge as a consequence of xenotransplantation, it might be several years before the problem was identified. During this time the infection might be spreading throughout the population; 3 viruses can mutate rapidly and thereby change their characteristics. 8 Mutation might allow animal viruses to infect human beings more readily; to resist attack by the human immune system; or to become drug-resistant; 4 one type of mutation occurs when viruses from different species recombine with each other and form new and possibly more dangerous viruses. It is thought that influenza epidemics are caused when new types of influenza virus are formed by recombination of two viruses, sometimes from different species. <strong>Xenotransplantation</strong> would provide increased opportunities for recombination between animal and human viruses; 5 one group of viruses, known as endogenous retroviruses, are inserted into the genetic material of the host animal and can be passed in this way from parent to offspring. This makes endogenous retroviruses almost impossible to eliminate from any animals that might be used as a source of organs for xenografting. It is possible that, after xenotransplantation, the endogenous retroviruses would move from the transplanted organs and become inserted into the genetic material of the human cells. Such insertion may cause mutations in the human genetic material and lead to an increased risk of cancer. 9 Comparison of the risks to human beings from infectious organisms of primates and pigs 6.10 The high degree of genetic relatedness of human beings and other primates means that infectious organisms from primates may have a good chance of surviving in, and causing disease in, human beings. Baboons, for example, carry several viruses with the potential to infect human beings including several herpes viruses (SA8, simian cytomegalovirus, and herpes papio) and several retroviruses (STLV-1, baboon endogenous retrovirus and foamy virus). 10 As mentioned above, there is considerable evidence that primates do indeed carry viruses that infect and cause disease in human beings (paragraph 6.5). These risks are reflected in the safety 8 This is especially likely for RNA viruses, including retroviruses, which replicate less faithfully than DNA viruses. 9 Stoye J P and Coffin J M (1995) The dangers of xenotransplantation. Letter to Nature Medicine, 1:1100. 10 Allan J S (1995) <strong>Xenotransplantation</strong> at a crossroads: Prevention versus progress. Nature Medicine, 2:18-21. 70
Transmission of infectious diseases precautions taken by people handling primates. 11 There is also experimental evidence that endogenous retroviruses from baboons can infect human cells. 12 Because the viruses from human beings and other primates are often closely related, the risk of recombination to form new harmful viruses, may be high (paragraph 6.9.4). Another problem is that to breed primates free from known viruses, in so far as this is possible, would require a long-term programme because of their relatively slow breeding rates (paragraph 4.34). As discussed below, there are certain to be primate viruses that are currently unidentified and which may have the potential to cause disease in human beings (paragraph 6.14). 6.11 In contrast, the more marked biological differences between pigs and human beings, and between their infectious organisms, may make it more difficult for infectious organisms from pigs to cause disease in human beings. Moreover, pigs have been domesticated and used by human beings for centuries, yet there is no evidence for transmission of viral diseases into the human population on the scale seen with viral diseases of other primates. Although the risks are likely to be lower, however, they cannot be ignored. Imutran Ltd, the UK firm developing transgenic pigs for xenotransplantation have pointed out that “the particular concern that xenografting raises is the risk of transmitting a pig pathogen to a human.” 13 Pig viruses with the potential to infect human beings include those causing porcine influenza, parainfluenza, swine vesicular disease, encephalomyocarditis and, possibly, pseudorabies. 14 Pigs, like primates, contain endogenous retroviruses and studies are needed to assess whether they can infect human cells. 15 Since they have a shorter generation time than primates, breeding pigs free of known viruses should prove more feasible. Pigs, however, will also contain viruses and other infectious organisms that have not yet been identified. Moreover, at least initially, recipients of pig xenografts might require high levels of immunosuppression which would render them very susceptible to infections. However, the hope is that, eventually, relatively low levels of immunosuppression could be used if organs are taken from transgenic pigs that have been genetically modified to reduce the immune response after transplantation. 16 11 Whitney R A and Wickings E J (1987) Macaques and other old world simians, Chapter 40 of The UFAW Handbook on the Care and Management of Laboratory Animals Sixth Edition. UK: Longman Scientific & Technical. 12 Benveniste R et al. (1974) Infectious type-C virus isolated from baboon placenta. Nature (London), 248:17-20. 13 Imutran Ltd: submission to the Working Party. 14 Onions D: submission to the Working Party. 15 Stoye J P and Coffin J M (1995) The dangers of xenotransplantation. Letter to Nature Medicine, 1:1100. 16 Cozzi E and White D J G (1995) The generation of transgenic pigs as potential organ donors for humans. Nature Medicine, 1:964-6. 71
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NUFFIELD COUNCIL ON BIOETHICS Anima
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Preface Preface Since the N
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Table of contents Table of contents
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Working Party on Xenografts Working
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Summary of recommendations Summary
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Summary of recommendations Effects
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The promise and the problems Chapte
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Alternatives to xenotransplantation
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Xenotransplantation - Nuffield Council on Bioethics

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