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 />
cerebral cortex, which is resp<strong>on</strong>sible for most higher brain functi<strong>on</strong>s such as thought and<br />
speech, is very poorly developed in <str<strong>on</strong>g>animals</str<strong>on</strong>g> other than primates. For example, individual<br />
nerve cells or groups <str<strong>on</strong>g>of</str<strong>on</strong>g> cells in the cortex <str<strong>on</strong>g>of</str<strong>on</strong>g> a c<strong>on</strong>scious m<strong>on</strong>key that are involved in<br />
anticipating a movement before it occurs can be distinguished from those cells that send the<br />
signal for the movement itself. In a similar way, it is possible to distinguish areas <str<strong>on</strong>g>of</str<strong>on</strong>g> the cortex<br />
involved in recognising the colour <str<strong>on</strong>g>of</str<strong>on</strong>g> an object from those involved in recognising moti<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
that object. Although n<strong>on</strong>-invasive imaging techniques such as magnetic res<strong>on</strong>ance imaging<br />
(MRI) and positr<strong>on</strong> emissi<strong>on</strong> tomography (PET) now allow the physiological activity <str<strong>on</strong>g>of</str<strong>on</strong>g> large<br />
groups <str<strong>on</strong>g>of</str<strong>on</strong>g> nerve cells in the human brain to be studied, the resoluti<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> these methods is<br />
still too poor to study individual nerve cells, or even small groups <str<strong>on</strong>g>of</str<strong>on</strong>g> nerve cells. Currently,<br />
therefore, the <strong>on</strong>ly way in which individual or small groups <str<strong>on</strong>g>of</str<strong>on</strong>g> cells can be studied is by<br />
inserting needle electrodes into the brain (see Box 5.4). N<strong>on</strong>etheless, imaging techniques are<br />
rapidly improving and are likely to provide increasingly powerful alternatives to invasive<br />
animal <str<strong>on</strong>g>research</str<strong>on</strong>g> <str<strong>on</strong>g>of</str<strong>on</strong>g> this type (see Box 11.1).<br />
Box 5.4: Example <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>research</str<strong>on</strong>g> – Studying<br />
c<strong>on</strong>trol and functi<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> the hand using<br />
primates<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<br />
some 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> establishment.<br />
<str<strong>on</strong>g>The</str<strong>on</strong>g> objective <str<strong>on</strong>g>of</str<strong>on</strong>g> this <str<strong>on</strong>g>research</str<strong>on</strong>g> <str<strong>on</strong>g>involving</str<strong>on</strong>g> macaque<br />
m<strong>on</strong>keys was to increase understanding <str<strong>on</strong>g>of</str<strong>on</strong>g> how a<br />
stroke can impair use <str<strong>on</strong>g>of</str<strong>on</strong>g> the hand in humans. It sought<br />
to investigate how activity in groups <str<strong>on</strong>g>of</str<strong>on</strong>g> brain cells in a<br />
part <str<strong>on</strong>g>of</str<strong>on</strong>g> the brain called the motor cortex c<strong>on</strong>trolled<br />
specific hand and finger movements. Primates were<br />
used because <strong>on</strong>ly these <str<strong>on</strong>g>animals</str<strong>on</strong>g> have a sufficiently<br />
similar brain structure, functi<strong>on</strong> and cognitive ability to<br />
ensure that the results were relevant to humans.<br />
Research <str<strong>on</strong>g>of</str<strong>on</strong>g> this type has recently made significant<br />
c<strong>on</strong>tributi<strong>on</strong>s to the diagnosis and therapy <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
movement disorders and has been crucial to the<br />
development <str<strong>on</strong>g>of</str<strong>on</strong>g> deep brain stimulati<strong>on</strong> (DBS), a new<br />
treatment for Parkins<strong>on</strong>’s disease.*<br />
<str<strong>on</strong>g>The</str<strong>on</strong>g> m<strong>on</strong>keys were procured from a breeding col<strong>on</strong>y in<br />
the UK where normal practice was to rear them in<br />
groups <str<strong>on</strong>g>of</str<strong>on</strong>g> 16–18 <str<strong>on</strong>g>animals</str<strong>on</strong>g> and accustom them to c<strong>on</strong>tact<br />
with humans. In the laboratory, the <str<strong>on</strong>g>animals</str<strong>on</strong>g> were<br />
housed in pairs from the age <str<strong>on</strong>g>of</str<strong>on</strong>g> 18 m<strong>on</strong>ths. <str<strong>on</strong>g>The</str<strong>on</strong>g> cages<br />
measured approximately 2.40x1.80x1.20m<br />
(width/height/depth) and c<strong>on</strong>tained objects for<br />
enrichment such as toys, mirrors, puzzle boxes and<br />
swings. Foraging material was provided in <strong>on</strong>e part <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
the cage. <str<strong>on</strong>g>The</str<strong>on</strong>g> room was lit with natural daylight<br />
through windows <strong>on</strong> two walls. In winter, the light was<br />
regulated <strong>on</strong> a 12-hour scheme with fading transiti<strong>on</strong>s.<br />
Researchers reported that they maintained frequent<br />
social c<strong>on</strong>tact with the m<strong>on</strong>keys.<br />
This project and the procedures were classified as<br />
‘moderate’ by the Home Office. <str<strong>on</strong>g>The</str<strong>on</strong>g> first procedure was<br />
usually an MRI scan. Under anaesthesia, threedimensi<strong>on</strong>al<br />
scans <str<strong>on</strong>g>of</str<strong>on</strong>g> the m<strong>on</strong>key’s skull and brain were<br />
taken. <str<strong>on</strong>g>The</str<strong>on</strong>g>se pictures aid the accurate targeting <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
areas <str<strong>on</strong>g>of</str<strong>on</strong>g> the brain from which recordings are made.<br />
<str<strong>on</strong>g>The</str<strong>on</strong>g> <str<strong>on</strong>g>animals</str<strong>on</strong>g> then underwent a period <str<strong>on</strong>g>of</str<strong>on</strong>g> training and<br />
learned that they would be rewarded with treats such<br />
as fruit, nuts and biscuits when they performed certain<br />
tasks correctly. Over a period <str<strong>on</strong>g>of</str<strong>on</strong>g> time, which varied<br />
between six and 12 m<strong>on</strong>ths, they were also trained to<br />
remain still while the <str<strong>on</strong>g>research</str<strong>on</strong>g> was being carried out,<br />
which required the use <str<strong>on</strong>g>of</str<strong>on</strong>g> some degree <str<strong>on</strong>g>of</str<strong>on</strong>g> restraint to<br />
which they became accustomed.<br />
<str<strong>on</strong>g>The</str<strong>on</strong>g> primary surgical interventi<strong>on</strong> was the implanting<br />
<str<strong>on</strong>g>of</str<strong>on</strong>g> devices necessary to record specific nerve-cell and<br />
muscle activity. Under general anaesthesia, a headrestraint<br />
device and recording chamber were fitted.<br />
<str<strong>on</strong>g>The</str<strong>on</strong>g> implants weighed 150g and c<strong>on</strong>sisted <str<strong>on</strong>g>of</str<strong>on</strong>g> a metal<br />
ring <str<strong>on</strong>g>of</str<strong>on</strong>g> approximately 10cm in diameter and 1mm in<br />
thickness, which was attached to the m<strong>on</strong>key’s head by<br />
means <str<strong>on</strong>g>of</str<strong>on</strong>g> four b<strong>on</strong>e screws <str<strong>on</strong>g>of</str<strong>on</strong>g> about 3mm diameter.<br />
<str<strong>on</strong>g>The</str<strong>on</strong>g> screws were inserted through holes made in the<br />
skull and were fixed <strong>on</strong> the inside. <str<strong>on</strong>g>The</str<strong>on</strong>g>se screws were<br />
subsequently used to attach the head <str<strong>on</strong>g>of</str<strong>on</strong>g> the m<strong>on</strong>key to<br />
a specially designed primate chair during an<br />
experimental procedure. During surgery, electrodes<br />
were also implanted to record the activity <str<strong>on</strong>g>of</str<strong>on</strong>g> the<br />
various nerve cells and muscles that are involved in<br />
moving the hand and arm.<br />
After surgery, m<strong>on</strong>keys received post-operative care<br />
including pain relieving medicines and antibiotics and<br />
were m<strong>on</strong>itored according to a regime approved by the<br />
named veterinary surge<strong>on</strong> (NVS). <str<strong>on</strong>g>The</str<strong>on</strong>g> average recovery<br />
time to normal behaviour was two to three days. <str<strong>on</strong>g>The</str<strong>on</strong>g><br />
recording procedure itself, which involved introducing<br />
very fine microelectrodes into the brain, is not painful,<br />
because the brain itself has no pain receptors. With<br />
regard to the psychological effects <strong>on</strong> the <str<strong>on</strong>g>animals</str<strong>on</strong>g>,<br />
there was usually a period <str<strong>on</strong>g>of</str<strong>on</strong>g> two to three days during<br />
recovery from surgery when the m<strong>on</strong>keys touched the<br />
implant. <str<strong>on</strong>g>The</str<strong>on</strong>g>y then became accustomed to it and<br />
stopped doing so.<br />
In order to allow for the recording <str<strong>on</strong>g>of</str<strong>on</strong>g> neural and<br />
muscular activity, the m<strong>on</strong>key was placed in a primate<br />
chair. This is a steel device, measuring approximately<br />
70x30x30cm. Once the m<strong>on</strong>key was seated in the chair,<br />
a metal disk was put over the ring attached to its skull,<br />
thereby immobilising the head by c<strong>on</strong>necting it to the<br />
chair. This is required to allow for the stable recording<br />
<str<strong>on</strong>g>of</str<strong>on</strong>g> the activity <str<strong>on</strong>g>of</str<strong>on</strong>g> single neur<strong>on</strong>es. <str<strong>on</strong>g>The</str<strong>on</strong>g> m<strong>on</strong>key<br />
remained able to move its jaw and chew, and the rest <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
C<strong>on</strong>tinued<br />
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