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 />
to insert human genes into the genome <str<strong>on</strong>g>of</str<strong>on</strong>g> mice to study, for example, their physiological<br />
role. Researchers working in the field believe that, in some cases, such experiments may<br />
yield more accurate animal models <str<strong>on</strong>g>of</str<strong>on</strong>g> human disease (see paragraph 6.35).<br />
7.4 <str<strong>on</strong>g>The</str<strong>on</strong>g> <str<strong>on</strong>g>animals</str<strong>on</strong>g> that are used most frequently to model the genetics <str<strong>on</strong>g>of</str<strong>on</strong>g> human disease are the<br />
mouse, rat and zebrafish. Virtually all <str<strong>on</strong>g>of</str<strong>on</strong>g> the GM <str<strong>on</strong>g>animals</str<strong>on</strong>g> used in experimental procedures in<br />
the UK during 2003 were from this group (see Appendix 2). 1 As we explain in more detail<br />
below, these three organisms have been chosen for a variety <str<strong>on</strong>g>of</str<strong>on</strong>g> reas<strong>on</strong>s.<br />
<str<strong>on</strong>g>The</str<strong>on</strong>g> mouse as a model for human disease<br />
7.5 <str<strong>on</strong>g>The</str<strong>on</strong>g> genetic modificati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> organisms such as the fruit fly Drosophila, the nematode worm<br />
C. elegans, yeast, bacteria and viruses can provide useful informati<strong>on</strong> <strong>on</strong> the fundamental<br />
biological role <str<strong>on</strong>g>of</str<strong>on</strong>g> genes. However, studies in these species cannot address questi<strong>on</strong>s that<br />
c<strong>on</strong>cern the effects <str<strong>on</strong>g>of</str<strong>on</strong>g> gene modificati<strong>on</strong> <strong>on</strong> the development <str<strong>on</strong>g>of</str<strong>on</strong>g> organs or physiological<br />
disease processes that are <strong>on</strong>ly found in vertebrates or mammals. <str<strong>on</strong>g>The</str<strong>on</strong>g> mouse is therefore<br />
increasingly the preferred organism for modelling the genetics <str<strong>on</strong>g>of</str<strong>on</strong>g> human disease. It is<br />
difficult to make an accurate current estimate <str<strong>on</strong>g>of</str<strong>on</strong>g> the total number <str<strong>on</strong>g>of</str<strong>on</strong>g> mouse mutant lines<br />
available in the world today but estimates suggest that there are more than 3,000. 2 <str<strong>on</strong>g>The</str<strong>on</strong>g>re<br />
are several approaches that are routinely used for manipulating the mouse genome and<br />
generating new GM mice, including:<br />
■ gene targeting by using ES cells (see paragraph 5.6);<br />
■ a mutagenesis programme using chemical mutagens followed by screening to identify<br />
relevant disease models (see paragraph 5.18); and<br />
■ new approaches, including the use <str<strong>on</strong>g>of</str<strong>on</strong>g> technologies to inactivate the RNA transcript <str<strong>on</strong>g>of</str<strong>on</strong>g> a<br />
gene so that it cannot be translated into a protein (RNA interference, or RNAi).<br />
Depending <strong>on</strong> the method used to produce mutati<strong>on</strong>s (see paragraphs 5.17–5.22), the<br />
number <str<strong>on</strong>g>of</str<strong>on</strong>g> mice that are required to establish a line carrying a specific mutati<strong>on</strong> varies from<br />
about 50 <str<strong>on</strong>g>animals</str<strong>on</strong>g> to several hundred. Additi<strong>on</strong>al <str<strong>on</strong>g>animals</str<strong>on</strong>g> will be required to investigate the<br />
phenotypic effects <str<strong>on</strong>g>of</str<strong>on</strong>g> any scientifically useful mutant that is created. Many large-scale<br />
<str<strong>on</strong>g>research</str<strong>on</strong>g> programmes <str<strong>on</strong>g>involving</str<strong>on</strong>g> these techniques are in progress at a number <str<strong>on</strong>g>of</str<strong>on</strong>g> centres<br />
around the world. One <str<strong>on</strong>g>of</str<strong>on</strong>g> the aims <str<strong>on</strong>g>of</str<strong>on</strong>g> the internati<strong>on</strong>al community <str<strong>on</strong>g>of</str<strong>on</strong>g> mouse geneticists is<br />
to develop at least <strong>on</strong>e mouse mutant line for every gene in the mouse genome over the<br />
next 20 years. <str<strong>on</strong>g>The</str<strong>on</strong>g> total number <str<strong>on</strong>g>of</str<strong>on</strong>g> mice that are expected to be used in mutagenesis and<br />
phenotyping studies is <str<strong>on</strong>g>of</str<strong>on</strong>g> the order <str<strong>on</strong>g>of</str<strong>on</strong>g> several milli<strong>on</strong> each year in the UK al<strong>on</strong>e (see<br />
paragraph 5.22). 3<br />
7.6 This use <str<strong>on</strong>g>of</str<strong>on</strong>g> GM <str<strong>on</strong>g>animals</str<strong>on</strong>g> for the study <str<strong>on</strong>g>of</str<strong>on</strong>g> human disease is rapidly expanding both in capacity<br />
and sophisticati<strong>on</strong>. A number <str<strong>on</strong>g>of</str<strong>on</strong>g> ‘mouse clinics’ are being built around the world with the<br />
space and tools to begin the analysis <str<strong>on</strong>g>of</str<strong>on</strong>g> the many thousands <str<strong>on</strong>g>of</str<strong>on</strong>g> mouse lines that will be<br />
developed. Ultimately, it is expected that highly detailed data that relate mutati<strong>on</strong>s in genes<br />
to different disease processes in the animal will be generated.<br />
1 GM <str<strong>on</strong>g>animals</str<strong>on</strong>g> were used in a total <str<strong>on</strong>g>of</str<strong>on</strong>g> 764,000 regulated procedures in 2003 (see paragraph 13.25). This figure comprises 27<br />
percent <str<strong>on</strong>g>of</str<strong>on</strong>g> all procedures for 2003. Ninety-eight percent <str<strong>on</strong>g>of</str<strong>on</strong>g> the procedures using GM <str<strong>on</strong>g>animals</str<strong>on</strong>g> involved rodents. Sixty-eight<br />
percent <str<strong>on</strong>g>of</str<strong>on</strong>g> the total number <str<strong>on</strong>g>of</str<strong>on</strong>g> GM <str<strong>on</strong>g>animals</str<strong>on</strong>g> were used for the maintenance <str<strong>on</strong>g>of</str<strong>on</strong>g> breeding col<strong>on</strong>ies but not for any further<br />
procedures. See Home Office (2004) Statistics <str<strong>on</strong>g>of</str<strong>on</strong>g> Scientific Procedures <strong>on</strong> Living Animals Great Britain 2003 (L<strong>on</strong>d<strong>on</strong>: HMSO).<br />
2 Abbott A (2004) Geneticists prepare for deluge <str<strong>on</strong>g>of</str<strong>on</strong>g> mutant mice Nature 432: 541<br />
3 For further informati<strong>on</strong>, see <str<strong>on</strong>g>The</str<strong>on</strong>g> Comprehensive Knockout Mouse Project C<strong>on</strong>sortium (2004) <str<strong>on</strong>g>The</str<strong>on</strong>g> Knockout Mouse Project Nat<br />
Genet 36: 921–4.<br />
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