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 />
<str<strong>on</strong>g>of</str<strong>on</strong>g> specific proteins in living cells and to analyse their activity. <str<strong>on</strong>g>The</str<strong>on</strong>g> cells expressing these<br />
fluorescent proteins can be readily visualised in tissue using a fluorescence microscope and<br />
purified using a fluorescence-activated cell sorter. Fluorescent proteins themselves are not<br />
known to cause adverse welfare effects. Mice can also be engineered to express a toxic<br />
protein in a specific cell type so that cells <str<strong>on</strong>g>of</str<strong>on</strong>g> this type can be eliminated by the body. This<br />
technique is used as an effective way <str<strong>on</strong>g>of</str<strong>on</strong>g> determining the normal functi<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> a particular type<br />
<str<strong>on</strong>g>of</str<strong>on</strong>g> cell. 13 Adverse effects <strong>on</strong> the animal would depend <strong>on</strong> the cell type that is eliminated.<br />
Research tools and techniques<br />
Producti<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> antibodies<br />
5.24 Antibodies are proteins that are widely used in many areas <str<strong>on</strong>g>of</str<strong>on</strong>g> biomedical <str<strong>on</strong>g>research</str<strong>on</strong>g>, as well as<br />
in clinical medicine. <str<strong>on</strong>g>The</str<strong>on</strong>g>y are highly useful tools, as each antibody type recognises the specific<br />
‘foreign’ molecule (antigen) against which it was produced. Antibodies <str<strong>on</strong>g>of</str<strong>on</strong>g> a particular type<br />
can therefore be used to identify, localise, quantify or purify an antigen. For example,<br />
antibodies might be labelled with fluorescent dyes and then used to locate specific molecules<br />
by fluorescence microscopy <str<strong>on</strong>g>of</str<strong>on</strong>g> tissues in vitro (i.e. in a tissue sample in the laboratory). <str<strong>on</strong>g>The</str<strong>on</strong>g>y<br />
can also be labelled with enzymes and used to quantify specific molecules in blood or other<br />
fluids or tissues, as for example in the comm<strong>on</strong> pregnancy test. Antibodies are also used to<br />
purify cells or molecules by attaching them to magnetic beads. <str<strong>on</strong>g>The</str<strong>on</strong>g> antibodies bound to the<br />
cells or molecules <str<strong>on</strong>g>of</str<strong>on</strong>g> interest can then be ‘attracted’ out <str<strong>on</strong>g>of</str<strong>on</strong>g> soluti<strong>on</strong>s.<br />
5.25 Antibodies are made by B lymphocytes, which develop in the b<strong>on</strong>e marrow. In order to<br />
produce antibodies against an antigen <str<strong>on</strong>g>of</str<strong>on</strong>g> interest, an animal (usually a mouse, rabbit, sheep<br />
or goat) is administered with the antigen <strong>on</strong>e or several times (immunised), together with a<br />
stimulant (an adjuvant), and the antibodies that are activated in resp<strong>on</strong>se are then collected<br />
from the blood. Adverse effects depend <strong>on</strong> the dose, frequency <str<strong>on</strong>g>of</str<strong>on</strong>g> injecti<strong>on</strong>s and the use <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
adjuvants, which can lead to irritati<strong>on</strong> and the formati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> an abscess. Immunisati<strong>on</strong> can<br />
also occasi<strong>on</strong>ally lead to a severe allergic reacti<strong>on</strong> (anaphylaxis), which can be fatal. If<br />
<str<strong>on</strong>g>animals</str<strong>on</strong>g> are used for the producti<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> purified m<strong>on</strong>ocl<strong>on</strong>al antibodies (the ascites method),<br />
then serious adverse effects can occur. This procedure is rarely used in the UK, although<br />
antibodies made by this method may be imported from abroad. 14<br />
Animal cl<strong>on</strong>ing<br />
5.26 <str<strong>on</strong>g>The</str<strong>on</strong>g> term cl<strong>on</strong>ing refers to the process <str<strong>on</strong>g>of</str<strong>on</strong>g> creating an identical copy <str<strong>on</strong>g>of</str<strong>on</strong>g> a gene, cell or a whole<br />
animal. Two types <str<strong>on</strong>g>of</str<strong>on</strong>g> cl<strong>on</strong>ing need to be distinguished: reproductive and therapeutic. <str<strong>on</strong>g>The</str<strong>on</strong>g><br />
former is used to produce an animal that is virtually genetically identical 15 to the predecessor<br />
from which it was cl<strong>on</strong>ed (see Figure 5.1 and Box 5.6).<br />
5.27 <str<strong>on</strong>g>The</str<strong>on</strong>g> main purpose <str<strong>on</strong>g>of</str<strong>on</strong>g> developing reproductive cl<strong>on</strong>ing techniques is to facilitate the targeted<br />
genetic modificati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>animals</str<strong>on</strong>g>. 16 Research also seeks to explore their potential for novel<br />
medical applicati<strong>on</strong>s such as providing organs for xenotransplantati<strong>on</strong> (see paragraph 1.18).<br />
In additi<strong>on</strong>, cl<strong>on</strong>ed <str<strong>on</strong>g>animals</str<strong>on</strong>g> could be used to rapidly increase the number <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>animals</str<strong>on</strong>g> <str<strong>on</strong>g>of</str<strong>on</strong>g> a<br />
genetically identical strain and therefore might replace repeated inbreeding (paragraph<br />
5.8). Cl<strong>on</strong>ed <str<strong>on</strong>g>animals</str<strong>on</strong>g> are being used to study age-related changes in cells, including cancers,<br />
13 <str<strong>on</strong>g>The</str<strong>on</strong>g> specific use <str<strong>on</strong>g>of</str<strong>on</strong>g> GM <str<strong>on</strong>g>animals</str<strong>on</strong>g> as disease models is discussed separately (see Chapter 7).<br />
14 No procedures were performed during 2003 in the UK using the ascites model. See Home Office (2004) Statistics <str<strong>on</strong>g>of</str<strong>on</strong>g> Scientific<br />
Procedures <strong>on</strong> Living Animals Great Britain 2003 (L<strong>on</strong>d<strong>on</strong>: HMSO).<br />
15 A very small fracti<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> DNA (16,500 base pairs out <str<strong>on</strong>g>of</str<strong>on</strong>g> a total <str<strong>on</strong>g>of</str<strong>on</strong>g> 3,000 milli<strong>on</strong> base pairs in the human genome) is external<br />
to the nucleus, and therefore comes from the d<strong>on</strong>or egg rather than the d<strong>on</strong>or nucleus.<br />
16 See Clark J and Whitelaw B (2003) A future for transgenic livestock Nat Rev Genet 4: 825–33.<br />
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