The ethics of research involving animals - Nuffield Council on ...
The ethics of research involving animals - Nuffield Council on ...
The ethics of research involving animals - Nuffield Council on ...
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T h e e t h i c s o f r e s e a r c h i n v o l v i n g a n i m a l s<br />
furthermore, that the spray caused adverse reacti<strong>on</strong>s. 33 It was then discovered that humans<br />
are in fact primarily infected via the digestive system and not through the nose. <str<strong>on</strong>g>The</str<strong>on</strong>g><br />
<str<strong>on</strong>g>research</str<strong>on</strong>g>ers had not fully understood the pathogenesis <str<strong>on</strong>g>of</str<strong>on</strong>g> the disease and wr<strong>on</strong>gly assumed<br />
that viral entry was via the nose. Thus, this error does not support the claim that polio is an<br />
example showing that, in principle, <str<strong>on</strong>g>animals</str<strong>on</strong>g> are unsuitable models for the disease. Rather, it<br />
indicates that failures in this case resulted from a false hypothesis made by the <str<strong>on</strong>g>research</str<strong>on</strong>g>ers.<br />
Diseases for which treatments and cures have been difficult to develop<br />
HIV/AIDS<br />
6.33 Mounting epidemiological evidence led to the recogniti<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> the infectious nature <str<strong>on</strong>g>of</str<strong>on</strong>g> the<br />
HIV/AIDS disease in the early 1980s. Shortly after, it was dem<strong>on</strong>strated through studies with<br />
chimpanzees that the primary disease-causing virus, HIV-1, was transmitted in blood and<br />
blood products and body fluids. <str<strong>on</strong>g>The</str<strong>on</strong>g>se findings revealed that nati<strong>on</strong>al blood banks were at<br />
high risk <str<strong>on</strong>g>of</str<strong>on</strong>g> providing c<strong>on</strong>taminated transfusi<strong>on</strong>s and transfusi<strong>on</strong> products to patients.<br />
Widespread screening <str<strong>on</strong>g>of</str<strong>on</strong>g> blood supplies was quickly initiated. Two major groups <str<strong>on</strong>g>of</str<strong>on</strong>g> HIV<br />
viruses, termed HIV-1 and HIV-2, were identified, each c<strong>on</strong>sisting <str<strong>on</strong>g>of</str<strong>on</strong>g> a complex range <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
variants. As the virus replicates in infected people and populati<strong>on</strong>s, it generates natural<br />
variants that c<strong>on</strong>tinuously escape and evade the human immune system. In additi<strong>on</strong>, the<br />
complexity <str<strong>on</strong>g>of</str<strong>on</strong>g> the virus within each pers<strong>on</strong> depends <strong>on</strong> their own genetic makeup so that<br />
within a populati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> infected people there develops a large variety <str<strong>on</strong>g>of</str<strong>on</strong>g> different types <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
HIV. This rapidly evolving virus populati<strong>on</strong> is a ’moving target’, and has become <strong>on</strong>e <str<strong>on</strong>g>of</str<strong>on</strong>g> the<br />
major scientific obstacles facing the medical <str<strong>on</strong>g>research</str<strong>on</strong>g> community. <str<strong>on</strong>g>The</str<strong>on</strong>g> virus also has complex<br />
interacti<strong>on</strong>s with a number <str<strong>on</strong>g>of</str<strong>on</strong>g> different types <str<strong>on</strong>g>of</str<strong>on</strong>g> cells within the body, particularly those that<br />
have a primary role in the immune system. For these reas<strong>on</strong>s it has not yet been possible to<br />
develop a vaccine or effective means <str<strong>on</strong>g>of</str<strong>on</strong>g> ridding the body <str<strong>on</strong>g>of</str<strong>on</strong>g> the virus.<br />
6.34 An ideal animal model for HIV-1/HIV-2 infecti<strong>on</strong> would have the following features:<br />
practicalities such as ease <str<strong>on</strong>g>of</str<strong>on</strong>g> handling and housing <str<strong>on</strong>g>of</str<strong>on</strong>g> the <str<strong>on</strong>g>animals</str<strong>on</strong>g>, a well-characterised<br />
physiology and immunology, and readily available species-specific reagents. It would also<br />
need to be susceptible to the form <str<strong>on</strong>g>of</str<strong>on</strong>g> HIV-1 that causes HIV/AIDS in humans or a very closely<br />
related virus. <str<strong>on</strong>g>The</str<strong>on</strong>g> model would require similar routes <str<strong>on</strong>g>of</str<strong>on</strong>g> infecti<strong>on</strong> and target cells, and<br />
should develop similar symptoms to those <str<strong>on</strong>g>of</str<strong>on</strong>g> the human disease. 34<br />
6.35 However, no single ideal animal model perfectly reproduces the symptoms <str<strong>on</strong>g>of</str<strong>on</strong>g> HIV-1 infecti<strong>on</strong><br />
and development <str<strong>on</strong>g>of</str<strong>on</strong>g> the disease in the diverse human populati<strong>on</strong>. <str<strong>on</strong>g>The</str<strong>on</strong>g> primate models that<br />
are currently available have inherent limitati<strong>on</strong>s. 35 Despite the fact that chimpanzees are<br />
naturally infected with the virus SIVcpz, which is the most likely forebear <str<strong>on</strong>g>of</str<strong>on</strong>g> HIV-1 in humans,<br />
they are resistant to AIDS. Some macaque species are infected by an HIV-2-related lentivirus<br />
called SIVsm, which causes a form <str<strong>on</strong>g>of</str<strong>on</strong>g> AIDS that closely resembles the human disease. In<br />
additi<strong>on</strong>, rhesus macaques are outbred like the human populati<strong>on</strong>, and have a similar<br />
spectrum <str<strong>on</strong>g>of</str<strong>on</strong>g> disease outcomes. But while similarities with humans and cross-reactive<br />
immunological reagents exist, the current human epidemic is predominantly caused by HIV-<br />
1 and therefore the model does not provide all the features needed. More recently, GM<br />
rodents engineered to express human receptors <strong>on</strong> their cells have provided replacements<br />
for primates in certain experiments. 36<br />
33 Rutty CJ (1996) <str<strong>on</strong>g>The</str<strong>on</strong>g> Middle-Class Plague: Epidemic Polio and the Canadian State, 1936-1937 Can Bull Med Hist 13: 277–314.<br />
34 Adapted from Lewis AD and Johns<strong>on</strong> PR (1995) Developing animal models for AIDS <str<strong>on</strong>g>research</str<strong>on</strong>g> – progress and problems Trends<br />
Biotechnol 13: 142–50.<br />
35 Lewis AD and Johns<strong>on</strong> PR (1995) Developing animal models for AIDS <str<strong>on</strong>g>research</str<strong>on</strong>g> – progress and problems Trends Biotechnol 13: 142–50.<br />
36 For example, see the descripti<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>research</str<strong>on</strong>g> at the Biomedical Primate Research Centre, available at:<br />
http://www.bprc.nl/BPRCE/L4/AltRep.html. Accessed <strong>on</strong>: 27 Apr 2005; Van Maanen M and Sutt<strong>on</strong> RE (2003) Rodent models<br />
for HIV-1 infecti<strong>on</strong> and disease Curr HIV Res 1: 121–30.<br />
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