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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 />

milli<strong>on</strong> people around the world per year. 28 Since the introducti<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> vaccines, polio has<br />

largely been eliminated from industrialised countries. 29<br />

6.30 It had l<strong>on</strong>g been thought that polio was infectious, and in 1908 two <str<strong>on</strong>g>research</str<strong>on</strong>g>ers aimed to<br />

induce polio in several <str<strong>on</strong>g>animals</str<strong>on</strong>g> by injecting them with extracts <str<strong>on</strong>g>of</str<strong>on</strong>g> spinal cord material from<br />

a boy who had died <str<strong>on</strong>g>of</str<strong>on</strong>g> the disease. While the extracts did not cause polio-like disease in<br />

rabbits, guinea pigs or mice, the disease manifested itself quickly in Old World m<strong>on</strong>keys.<br />

Later, <str<strong>on</strong>g>research</str<strong>on</strong>g>ers were able to transmit polio from m<strong>on</strong>key to m<strong>on</strong>key by the injecti<strong>on</strong><br />

<str<strong>on</strong>g>of</str<strong>on</strong>g> extracts <str<strong>on</strong>g>of</str<strong>on</strong>g> diseased spinal cord. Thus the virus could be propagated and an animal model<br />

<str<strong>on</strong>g>of</str<strong>on</strong>g> the disease was created. Use <str<strong>on</strong>g>of</str<strong>on</strong>g> this animal model in further studies led to the<br />

identificati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> the polio virus. Welfare implicati<strong>on</strong>s for <str<strong>on</strong>g>animals</str<strong>on</strong>g> used in this early <str<strong>on</strong>g>research</str<strong>on</strong>g><br />

extended over a broad range, but could be expected to resemble some <str<strong>on</strong>g>of</str<strong>on</strong>g> the symptoms<br />

experienced by humans.<br />

6.31 In 1939, <str<strong>on</strong>g>research</str<strong>on</strong>g>ers were able to adapt <strong>on</strong>e <str<strong>on</strong>g>of</str<strong>on</strong>g> the strains <str<strong>on</strong>g>of</str<strong>on</strong>g> the polio virus to make it<br />

infectious to mice, thus creating a more c<strong>on</strong>venient rodent model for the disease. In the 1940s,<br />

<str<strong>on</strong>g>research</str<strong>on</strong>g>ers who were subsequently awarded a Nobel Prize dem<strong>on</strong>strated that the polio virus<br />

could be grown in cultured human cells, a property essential for future <str<strong>on</strong>g>research</str<strong>on</strong>g> <strong>on</strong> the virus.<br />

It was still not possible to observe the virus under the microscope at that time. <str<strong>on</strong>g>The</str<strong>on</strong>g>refore, in<br />

order to c<strong>on</strong>firm that the virus did propagate in cultured tissue, fluid was injected from the<br />

cultures into <str<strong>on</strong>g>animals</str<strong>on</strong>g> to observe if the disease developed. 30 In 1949, <str<strong>on</strong>g>research</str<strong>on</strong>g> <strong>on</strong> rodent models<br />

showed that there are in fact three types <str<strong>on</strong>g>of</str<strong>on</strong>g> polio virus. 31 In the 1950s Dr J<strong>on</strong>as Salk used<br />

cultured m<strong>on</strong>key kidney cells to grow the virus. He then used the virus particles to produce the<br />

first vaccine which was found to be very effective at preventing the disease in humans,<br />

although people could still carry and spread the virus if it invaded their intestinal tract. In the<br />

1960s, a new oral vaccine against the disease was developed. This vaccine c<strong>on</strong>tained live virus<br />

which had been ‘attenuated’, or weakened, by repeatedly growing it in cultured m<strong>on</strong>key cells.<br />

<str<strong>on</strong>g>The</str<strong>on</strong>g> vaccine produced an adequate immune resp<strong>on</strong>se without causing an infecti<strong>on</strong>. <str<strong>on</strong>g>The</str<strong>on</strong>g> live<br />

attenuated virus, however, can sometimes revert to a virulent form and cause infecti<strong>on</strong>.<br />

Animals are currently used to test the potential virulence <str<strong>on</strong>g>of</str<strong>on</strong>g> each batch <str<strong>on</strong>g>of</str<strong>on</strong>g> vaccine that is<br />

produced to overcome the problem <str<strong>on</strong>g>of</str<strong>on</strong>g> occasi<strong>on</strong>al vaccine-associated poliomyelitis (see Box 8.5).<br />

6.32 Mice and m<strong>on</strong>keys were used during important stages <str<strong>on</strong>g>of</str<strong>on</strong>g> the study <str<strong>on</strong>g>of</str<strong>on</strong>g> polio and the<br />

subsequent development <str<strong>on</strong>g>of</str<strong>on</strong>g> the vaccine. However, the initial development <str<strong>on</strong>g>of</str<strong>on</strong>g> the polio<br />

vaccine is regarded by some as an example which shows that animal <str<strong>on</strong>g>research</str<strong>on</strong>g> is misleading. 32<br />

<str<strong>on</strong>g>The</str<strong>on</strong>g> early <str<strong>on</strong>g>research</str<strong>on</strong>g> was c<strong>on</strong>troversial because, in the first half <str<strong>on</strong>g>of</str<strong>on</strong>g> the 20th century, the<br />

dominant scientific theory was that the polio virus entered the body through the olfactory<br />

nerves <str<strong>on</strong>g>of</str<strong>on</strong>g> the nose, as indicated by experiments in m<strong>on</strong>keys. Scientists, particularly in the USA<br />

and Canada, inferred from these observati<strong>on</strong>s that it would be useful to develop<br />

prophylactic nasal sprays. <str<strong>on</strong>g>The</str<strong>on</strong>g> sprays were tested <strong>on</strong> <str<strong>on</strong>g>animals</str<strong>on</strong>g> and then <strong>on</strong> humans. In <strong>on</strong>e<br />

large-scale trial in Tor<strong>on</strong>to in 1937, the spray was tested <strong>on</strong> 5,000 children. <str<strong>on</strong>g>The</str<strong>on</strong>g> trial results<br />

so<strong>on</strong> revealed that the spray was ineffective as a preventative for infecti<strong>on</strong> by the virus and,<br />

CHAPTER 6 THE USE OF ANIMALS IN THE STUDY OF HUMAN DISEASE<br />

28 Eggers HJ (1999) Milest<strong>on</strong>es in early poliomyelitis <str<strong>on</strong>g>research</str<strong>on</strong>g> (1840 to 1949) J Virol 73: 4533–5.<br />

29 <str<strong>on</strong>g>The</str<strong>on</strong>g> World Health Organizati<strong>on</strong> has recently estimated that polio would be eliminated during 2004–5, although similar<br />

statements have been made before. In 2003 there were 784 c<strong>on</strong>firmed cases <str<strong>on</strong>g>of</str<strong>on</strong>g> the virus, mostly occurring in Africa and<br />

south-east Asia, particularly in Nigeria, India and Pakistan. See World Health Organizati<strong>on</strong> Polio Eradicati<strong>on</strong>, available at:<br />

http://www.polioeradicati<strong>on</strong>.org/; Polio Case Count, available at: http://www.who.int/vaccines/casecount/case_count.cfm.<br />

Accessed <strong>on</strong>: 26 Apr 2005.<br />

30 For a mini-review <str<strong>on</strong>g>of</str<strong>on</strong>g> early polio <str<strong>on</strong>g>research</str<strong>on</strong>g> see Eggers HJ (1999) Milest<strong>on</strong>es in early poliomyelitis <str<strong>on</strong>g>research</str<strong>on</strong>g> (1840 to 1949) J<br />

Virol 73: 4533–5.<br />

31 Current vaccines c<strong>on</strong>tain a mixture <str<strong>on</strong>g>of</str<strong>on</strong>g> the three types which together c<strong>on</strong>fer immunity.<br />

32 See Paul JR (1971) A history <str<strong>on</strong>g>of</str<strong>on</strong>g> poliomyelitis (New Haven and L<strong>on</strong>d<strong>on</strong>: Yale University Press).<br />

115

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