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 />
the body was free to move. <str<strong>on</strong>g>The</str<strong>on</strong>g> m<strong>on</strong>key appeared not<br />
to resist this procedure (see paragraph 3.34). <str<strong>on</strong>g>The</str<strong>on</strong>g><br />
multiple electrodes inserted through the implanted<br />
recording chamber into the m<strong>on</strong>key’s brain were<br />
c<strong>on</strong>nected with wires to a computer, and to devices<br />
recording the activity <str<strong>on</strong>g>of</str<strong>on</strong>g> muscles in the arm and hand.<br />
With regard to the experimental procedure itself, the<br />
standard task required the m<strong>on</strong>key to perform a highly<br />
skilled hand movement, using its thumb and index<br />
finger to squeeze two levers into precise target z<strong>on</strong>es.<br />
Each time it squeezed the levers successfully, it was<br />
given a food reward by an animal technician sitting<br />
next to the m<strong>on</strong>key. Once <str<strong>on</strong>g>research</str<strong>on</strong>g>ers had obtained<br />
sufficient data <strong>on</strong> the c<strong>on</strong>necti<strong>on</strong> between certain<br />
neural areas <str<strong>on</strong>g>of</str<strong>on</strong>g> the motor cortex and hand movements,<br />
the electrodes were inserted into a new area <str<strong>on</strong>g>of</str<strong>on</strong>g> the<br />
brain. <str<strong>on</strong>g>The</str<strong>on</strong>g>re were typically three to five sessi<strong>on</strong>s per<br />
week, with regular breaks <str<strong>on</strong>g>of</str<strong>on</strong>g> three to four weeks. Each<br />
sessi<strong>on</strong> lasted approximately three hours, during which<br />
a m<strong>on</strong>key received around 600 food rewards. On<br />
average, each m<strong>on</strong>key provided 100–200 fully analysed<br />
neur<strong>on</strong>es over 18 m<strong>on</strong>ths. Animals were killed at the<br />
end <str<strong>on</strong>g>of</str<strong>on</strong>g> this period by administering deep general<br />
anaesthesia from which they did not recover. This<br />
Studies <str<strong>on</strong>g>of</str<strong>on</strong>g> animal development<br />
5.12 Developmental biologists <str<strong>on</strong>g>of</str<strong>on</strong>g>ten carry out experiments <strong>on</strong> embryos to determine the<br />
cellular and molecular basis <str<strong>on</strong>g>of</str<strong>on</strong>g> animal development. Parts <str<strong>on</strong>g>of</str<strong>on</strong>g> an embryo (<str<strong>on</strong>g>of</str<strong>on</strong>g>ten chick<br />
embryos) are removed to learn about how different tissues develop (see Box 5.5). In some<br />
cases, a fragment <str<strong>on</strong>g>of</str<strong>on</strong>g> tissue is transferred to a new locati<strong>on</strong> in the embryo to observe its<br />
development. <str<strong>on</strong>g>The</str<strong>on</strong>g> outcome indicates whether or not the tissue was already irreversibly<br />
programmed for development into a particular tissue or organ at the time <str<strong>on</strong>g>of</str<strong>on</strong>g> transfer. A<br />
dye might also be injected into <strong>on</strong>e or more cells, to enable observati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> their stages<br />
<str<strong>on</strong>g>of</str<strong>on</strong>g> development. Zebrafish embryos are <str<strong>on</strong>g>of</str<strong>on</strong>g>ten used because they are transparent, which<br />
is a useful property with regard to m<strong>on</strong>itoring the development <str<strong>on</strong>g>of</str<strong>on</strong>g> injected cells in the<br />
living embryo.<br />
Box 5.5: Example <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>research</str<strong>on</strong>g> –<br />
Developmental studies <str<strong>on</strong>g>involving</str<strong>on</strong>g> amphibians<br />
This is an example <str<strong>on</strong>g>of</str<strong>on</strong>g> animal <str<strong>on</strong>g>research</str<strong>on</strong>g> witnessed by some<br />
members <str<strong>on</strong>g>of</str<strong>on</strong>g> the Working Party during a visit to a<br />
<str<strong>on</strong>g>research</str<strong>on</strong>g> laboratory. <str<strong>on</strong>g>The</str<strong>on</strong>g> main focus <str<strong>on</strong>g>of</str<strong>on</strong>g> the <str<strong>on</strong>g>research</str<strong>on</strong>g> was<br />
to improve understanding <str<strong>on</strong>g>of</str<strong>on</strong>g> the processes that<br />
determine cell differentiati<strong>on</strong> during the early stages <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
embry<strong>on</strong>ic development. Researchers used two different<br />
species in order to provide comparable informati<strong>on</strong>.<br />
Amphibian embryos were preferred to mammalian<br />
models such as the mouse because amphibians produce a<br />
large number <str<strong>on</strong>g>of</str<strong>on</strong>g> eggs that develop externally to the<br />
mother, are <str<strong>on</strong>g>of</str<strong>on</strong>g> a size which allows experimental reagents<br />
to be injected easily, and develop fairly rapidly. <str<strong>on</strong>g>The</str<strong>on</strong>g><br />
<str<strong>on</strong>g>research</str<strong>on</strong>g> was undertaken <strong>on</strong> embryos <str<strong>on</strong>g>of</str<strong>on</strong>g> the frogs<br />
Xenopus laevis and Xenopus tropicalis. In general, the<br />
results gained from developmental studies <strong>on</strong> these frogs<br />
are c<strong>on</strong>sidered to be readily transferable to mammals,<br />
including humans, as most <str<strong>on</strong>g>of</str<strong>on</strong>g> the basic developmental<br />
mechanisms have been highly c<strong>on</strong>served in evoluti<strong>on</strong>.<br />
allowed electrophysiological and neuroanatomical<br />
investigati<strong>on</strong>s <str<strong>on</strong>g>of</str<strong>on</strong>g> brain pathways involved in hand<br />
c<strong>on</strong>trol which enabled the scientists to verify the<br />
anatomical positi<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> the electrodes that had been<br />
inserted during the <str<strong>on</strong>g>research</str<strong>on</strong>g>. At this particular<br />
laboratory, approximately <strong>on</strong>e m<strong>on</strong>key per year was<br />
used for this type <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>research</str<strong>on</strong>g>.<br />
* DBS involves the implantati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> small stimulating<br />
electrodes <str<strong>on</strong>g>of</str<strong>on</strong>g> approximately 1x3mm in the brain circuits <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
patients suffering from Parkins<strong>on</strong>’s disease. <str<strong>on</strong>g>The</str<strong>on</strong>g> electrodes<br />
are c<strong>on</strong>nected with wires to a unit implanted close to the<br />
collar b<strong>on</strong>e. This unit generates electrical impulses in a<br />
method similar to pacemakers. To date, approximately<br />
22,000 patients have been treated with DBS. <str<strong>on</strong>g>The</str<strong>on</strong>g> technique<br />
helps to reduce dramatically the manifestati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> tremors,<br />
episodes <str<strong>on</strong>g>of</str<strong>on</strong>g> spasticity and other forms <str<strong>on</strong>g>of</str<strong>on</strong>g> abnormal<br />
movement typically experienced by sufferers <str<strong>on</strong>g>of</str<strong>on</strong>g> Parkins<strong>on</strong>’s<br />
disease. See Rodriguez-Oroz MC, Zamarbide I, Guridi J,<br />
Palmero MR and Obeso JA (2004) Efficacy <str<strong>on</strong>g>of</str<strong>on</strong>g> deep brain<br />
stimulati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> the subthalamic nucleus in Parkins<strong>on</strong>’s<br />
disease four years after surgery: double blind and open<br />
label evaluati<strong>on</strong> J Neurol Neurosurg Psychiatry 75: 1382–5;<br />
Kumar R, Lozano AM, Kim YJ et al. (1998) Double-blind<br />
evaluati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> subthalamic nucleus deep brain stimulati<strong>on</strong> in<br />
advanced Parkins<strong>on</strong>’s disease Neurology 51: 850–5.<br />
<str<strong>on</strong>g>The</str<strong>on</strong>g> stimulati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> egg-laying was the <strong>on</strong>ly procedure<br />
undertaken in this study that fell under the A(SP)A. Adult<br />
female frogs were injected with a horm<strong>on</strong>e that caused<br />
them to lay large numbers <str<strong>on</strong>g>of</str<strong>on</strong>g> eggs within 3-12 hours. This<br />
involved a subcutaneous injecti<strong>on</strong> just over the dorsal<br />
lymph sac. <str<strong>on</strong>g>The</str<strong>on</strong>g> eggs were fertilised artificially to ensure<br />
synchr<strong>on</strong>ous development. In order to do so, a male frog<br />
was killed by methods referred to in Schedule 1 <str<strong>on</strong>g>of</str<strong>on</strong>g> the<br />
A(SP)A, and its testes was removed and used to fertilise<br />
the eggs. Female frogs generate more eggs over a four<br />
m<strong>on</strong>th rest period and are reused in the procedure<br />
described above for the producti<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> new eggs.<br />
<str<strong>on</strong>g>The</str<strong>on</strong>g> frogs were kept in a windowless room in three rows<br />
<str<strong>on</strong>g>of</str<strong>on</strong>g> five basins, each measuring approximately<br />
60x40x30cm. <str<strong>on</strong>g>The</str<strong>on</strong>g>re were between five and 25 frogs per<br />
tank, each frog having a minimum <str<strong>on</strong>g>of</str<strong>on</strong>g> <strong>on</strong>e litre <str<strong>on</strong>g>of</str<strong>on</strong>g> water.<br />
<str<strong>on</strong>g>The</str<strong>on</strong>g> water was changed daily. No enrichments were<br />
provided in the tanks. <str<strong>on</strong>g>The</str<strong>on</strong>g> room light operated <strong>on</strong> a 12-<br />
hour cycle, with gradual transiti<strong>on</strong>s between light and<br />
darkness.<br />
CHAPTER 5 THE USE OF ANIMALS IN BASIC BIOLOGICAL RESEARCH<br />
95