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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 />

fact that some mice used in this type <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>research</str<strong>on</strong>g> are allowed to age. <str<strong>on</strong>g>The</str<strong>on</strong>g>y may therefore<br />

show signs related to old age, such as abscesses, starey coats (not lying flat) or holding<br />

their tails abnormally.<br />

6.17 Similar experimental studies have dem<strong>on</strong>strated the transmissibility <str<strong>on</strong>g>of</str<strong>on</strong>g> BSE between cattle,<br />

sheep and primates. Transmissi<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> BSE to m<strong>on</strong>keys by injecti<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> bovine pri<strong>on</strong>s into the<br />

brains <str<strong>on</strong>g>of</str<strong>on</strong>g> macaques was the first dem<strong>on</strong>strati<strong>on</strong> that BSE was able to cross the species barrier<br />

from ruminants to primates. <str<strong>on</strong>g>The</str<strong>on</strong>g>se experiments, undertaken in 1996 in the UK and France,<br />

were a forewarning that BSE might be transmissible to humans.<br />

6.18 As there is no immune resp<strong>on</strong>se to pri<strong>on</strong> infecti<strong>on</strong>, it has not yet been possible to develop<br />

diagnostic tests that dem<strong>on</strong>strate the presence <str<strong>on</strong>g>of</str<strong>on</strong>g> the disease before symptoms occur.<br />

Although there is now a range <str<strong>on</strong>g>of</str<strong>on</strong>g> biochemical markers for detecting the abnormal protein<br />

in potentially affected tissues, infecti<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> mice remains the accepted standard for<br />

diagnosing pri<strong>on</strong> diseases.<br />

6.19 In view <str<strong>on</strong>g>of</str<strong>on</strong>g> the potential number <str<strong>on</strong>g>of</str<strong>on</strong>g> human cases, it is important to develop interventi<strong>on</strong><br />

strategies aimed at slowing down or preventing the spread <str<strong>on</strong>g>of</str<strong>on</strong>g> pri<strong>on</strong>s. This may eventually be<br />

achieved by treatment with medicines or through the development <str<strong>on</strong>g>of</str<strong>on</strong>g> a vaccine. A vaccine<br />

could theoretically stimulate the producti<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> antibodies to PrPsc, thus preventing pri<strong>on</strong><br />

proteins from spreading in vivo. Scientists using <str<strong>on</strong>g>animals</str<strong>on</strong>g> in <str<strong>on</strong>g>research</str<strong>on</strong>g> with this aim assert that<br />

the development <str<strong>on</strong>g>of</str<strong>on</strong>g> effective therapeutic strategies is likely to depend <strong>on</strong> c<strong>on</strong>tinued<br />

<str<strong>on</strong>g>research</str<strong>on</strong>g> <strong>on</strong> <str<strong>on</strong>g>animals</str<strong>on</strong>g>.<br />

<str<strong>on</strong>g>The</str<strong>on</strong>g> c<strong>on</strong>tributi<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> animal models for TSEs to public health policy<br />

6.20 <str<strong>on</strong>g>The</str<strong>on</strong>g> in vivo models for the pathogenesis <str<strong>on</strong>g>of</str<strong>on</strong>g> TSEs have had decisive influence <strong>on</strong> the<br />

development <str<strong>on</strong>g>of</str<strong>on</strong>g> policies for public health aimed at c<strong>on</strong>trolling these diseases in cattle and<br />

sheep, and to protect humans from further exposure to agents <str<strong>on</strong>g>of</str<strong>on</strong>g> animal TSEs. 19 <str<strong>on</strong>g>The</str<strong>on</strong>g> current<br />

public health measures are based <strong>on</strong> evidence obtained from experiments <strong>on</strong> the<br />

pathogenesis <str<strong>on</strong>g>of</str<strong>on</strong>g> TSEs in cattle, sheep, pigs and chickens. Without these studies, it would have<br />

been difficult to know how to devise and implement public health measures, other than to<br />

prohibit the eating <str<strong>on</strong>g>of</str<strong>on</strong>g> any animal products, since, at the time, <str<strong>on</strong>g>research</str<strong>on</strong>g>ers were not able to<br />

undertake the <str<strong>on</strong>g>research</str<strong>on</strong>g> by alternative, n<strong>on</strong>-animal methods.<br />

BSE pathogenesis and public health measures<br />

6.21 In several large-scale studies <strong>on</strong> the pathogenesis <str<strong>on</strong>g>of</str<strong>on</strong>g> BSE, scientists infected calves by feeding<br />

them with an extract <str<strong>on</strong>g>of</str<strong>on</strong>g> cow brain taken from an animal with the disease. <str<strong>on</strong>g>The</str<strong>on</strong>g> spread <str<strong>on</strong>g>of</str<strong>on</strong>g><br />

infectivity was then m<strong>on</strong>itored in various tissues. Infectivity was determined by<br />

administering extracts <str<strong>on</strong>g>of</str<strong>on</strong>g> tissue to mice and assessing if they develop the disease (see<br />

paragraph 6.18). Several hundred cattle and several thousand mice were used in these<br />

experiments. <str<strong>on</strong>g>The</str<strong>on</strong>g>se studies established unequivocally that BSE replicates early <strong>on</strong> in the gut<br />

lymphoid tissues and then spreads to other lymphoid tissue and via major nerves to the CNS.<br />

<str<strong>on</strong>g>The</str<strong>on</strong>g> highest levels <str<strong>on</strong>g>of</str<strong>on</strong>g> infectivity were found in gut-associated lymphoid tissue, major nerves<br />

in the head and neck, brain, spinal cord and collecti<strong>on</strong>s <str<strong>on</strong>g>of</str<strong>on</strong>g> nerve cells embedded in the<br />

vertebral column known as the dorsal root ganglia. Little infectivity was detected in skeletal<br />

muscles. 20<br />

19 Experimental transmissi<strong>on</strong> studies in pigs and chickens, for example, showed that these <str<strong>on</strong>g>animals</str<strong>on</strong>g> are not susceptible to BSE<br />

when fed infected tissue, thus allaying fears that pigs and poultry, which were also exposed to infective MBM, could be<br />

infectious for humans through the food chain.<br />

20 <str<strong>on</strong>g>The</str<strong>on</strong>g> BSE Enquiry (2000) Report <str<strong>on</strong>g>of</str<strong>on</strong>g> the BSE Enquiry, Volume 2, Chapter 3, available at:<br />

http://www.bseinquiry.gov.uk/report/volume2/chaptea8.htm#821257. Accessed <strong>on</strong>: 26 Apr 2005.<br />

112

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