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 />
Producti<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> tools<br />
10.9 Animals are widely used for the producti<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> antibodies, which can be employed to identify,<br />
localise, quantify or purify a substance. To produce antibodies against an antigen <str<strong>on</strong>g>of</str<strong>on</strong>g> interest,<br />
an animal is repeatedly immunised with the antigen together with an immunostimulant (an<br />
adjuvant), and the antibodies are then harvested from the blood. <str<strong>on</strong>g>The</str<strong>on</strong>g> use <str<strong>on</strong>g>of</str<strong>on</strong>g> adjuvants in<br />
<str<strong>on</strong>g>animals</str<strong>on</strong>g> (which are not always required) can lead to the development <str<strong>on</strong>g>of</str<strong>on</strong>g> sterile abscesses or<br />
lameness after intramuscular injecti<strong>on</strong>s into the leg. Immunisati<strong>on</strong> can sometimes cause<br />
anaphylaxis which can be lethal. <str<strong>on</strong>g>The</str<strong>on</strong>g> use <str<strong>on</strong>g>of</str<strong>on</strong>g> mice, primed with an irritant, to produce large<br />
amounts <str<strong>on</strong>g>of</str<strong>on</strong>g> a m<strong>on</strong>ocl<strong>on</strong>al antibody in ascitic fluid in the perit<strong>on</strong>eal cavity is now rarely used in<br />
the UK; it has been replaced by an in vitro method.<br />
Animals in the study <str<strong>on</strong>g>of</str<strong>on</strong>g> human disease (Chapter 6)<br />
10.10 Animals are used for the study <str<strong>on</strong>g>of</str<strong>on</strong>g> diseases affecting <str<strong>on</strong>g>animals</str<strong>on</strong>g> and humans to learn about causal<br />
factors, development and infectivity, and to explore therapeutic and preventative strategies.<br />
Many diseases induce complex and dynamic interacti<strong>on</strong>s between molecular, cellular and<br />
organ systems. Although in vitro experiments form an important part <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>research</str<strong>on</strong>g> <strong>on</strong> diseases,<br />
scientists whose work involves <str<strong>on</strong>g>animals</str<strong>on</strong>g> emphasise that their work is crucial in understanding<br />
the interacti<strong>on</strong>s <str<strong>on</strong>g>of</str<strong>on</strong>g> these complex processes. Disease models can be obtained by discovery <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
sp<strong>on</strong>taneous mutati<strong>on</strong>s, by selective breeding or by means <str<strong>on</strong>g>of</str<strong>on</strong>g> more targeted interventi<strong>on</strong>s<br />
such as genetic modificati<strong>on</strong> (paragraphs 10.16-10.18). If <str<strong>on</strong>g>animals</str<strong>on</strong>g> are to provide useful models,<br />
it is <strong>on</strong>ly important that relevant elements <str<strong>on</strong>g>of</str<strong>on</strong>g> their bodily processes are similar to those <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
humans. In some cases this may mean that although <str<strong>on</strong>g>animals</str<strong>on</strong>g> can be useful models for the<br />
study <str<strong>on</strong>g>of</str<strong>on</strong>g> diseases that cause great suffering in humans, the <str<strong>on</strong>g>animals</str<strong>on</strong>g> used may not experience<br />
the same level <str<strong>on</strong>g>of</str<strong>on</strong>g> discomfort. In others, <str<strong>on</strong>g>animals</str<strong>on</strong>g> may spend much (or all) their lives suffering<br />
from the animal form <str<strong>on</strong>g>of</str<strong>on</strong>g> the disease under study.<br />
CHAPTER 10 SUMMARY OF SECTION 2<br />
10.11 We described two recently developed disease models for rheumatoid arthritis (RA) and<br />
transmissible sp<strong>on</strong>giform encephalopathies (TSEs). RA is <strong>on</strong>e <str<strong>on</strong>g>of</str<strong>on</strong>g> the most comm<strong>on</strong> human<br />
autoimmune diseases. It is a crippling disease resulting in chr<strong>on</strong>ic inflammati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> the joints,<br />
the cause <str<strong>on</strong>g>of</str<strong>on</strong>g> which remains unknown. In the last ten years there have been major advances in<br />
the understanding <str<strong>on</strong>g>of</str<strong>on</strong>g> the disease process. Both animal and n<strong>on</strong>-animal approaches to <str<strong>on</strong>g>research</str<strong>on</strong>g><br />
have been pursued simultaneously and <str<strong>on</strong>g>of</str<strong>on</strong>g>ten by the same <str<strong>on</strong>g>research</str<strong>on</strong>g>ers (paragraph 6.5). Study<br />
<str<strong>on</strong>g>of</str<strong>on</strong>g> rodent models with induced arthritis helped to c<strong>on</strong>tribute to the discovery that an immune<br />
molecule called TNF plays a crucial role in the inflammatory process. <str<strong>on</strong>g>The</str<strong>on</strong>g> <str<strong>on</strong>g>animals</str<strong>on</strong>g> experienced<br />
a painful swelling <str<strong>on</strong>g>of</str<strong>on</strong>g> the paws, and damage to the cartilage which would have affected the<br />
<str<strong>on</strong>g>animals</str<strong>on</strong>g>’ welfare since rodents use their fr<strong>on</strong>t feet extensively for grooming, holding food,<br />
eating and moving around. Various interventi<strong>on</strong>s were tested <strong>on</strong> the models, aimed at<br />
neutralising the inflammatory reacti<strong>on</strong>s by blocking the molecule through administrati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
antibodies. This strategy had dramatic effects <strong>on</strong> reducing the inflammati<strong>on</strong> and damage<br />
caused by the disease in mice. In the early 1990s, clinical trials were carried out in humans and<br />
proved successful (see paragraphs 6.9-6.10). Some 200,000 people have since been treated<br />
effectively with the antibody therapy.<br />
10.12 When BSE emerged in cattle in the mid-1980s little was known about its causes and<br />
infectivity (paragraph 6.12). Experimental <str<strong>on</strong>g>animals</str<strong>on</strong>g> were used to test the novel hypothesis<br />
that the disease was caused by abnormal forms <str<strong>on</strong>g>of</str<strong>on</strong>g> a protein, called pri<strong>on</strong>s. Transmissi<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
BSE to m<strong>on</strong>keys by injecting bovine pri<strong>on</strong>s into their brains was the first dem<strong>on</strong>strati<strong>on</strong> that<br />
the disease was able to cross the species barrier to primates, and ultimately also to humans.<br />
In 1996, the first cases <str<strong>on</strong>g>of</str<strong>on</strong>g> vCJD occurred in people in the UK who had been exposed to the<br />
BSE agent. Experiments using mice were used to define important stages in the<br />
development <str<strong>on</strong>g>of</str<strong>on</strong>g> sp<strong>on</strong>giform encephalopathies. <str<strong>on</strong>g>The</str<strong>on</strong>g> mice typically experienced progressive<br />
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