"... any experimental or other scientific procedure applied to a protected animal which may have the effect of causing that animal pain, suffering, distress or lasting harm."
"In determining whether any procedure may have the effect mentioned in subsection (1) above the use of an anaesthetic or analgesic, decerebration and any other procedure for rendering an animal insentient shall be disregarded; and the administration of an anaesthetic or analgesic to a protected animal, or decerebration or any other such procedure applied to such an animal, for the purposes of any experimental or other scientific procedure shall itself be a regulated procedure."
"Killing a protected animal is a regulated procedure only if it is killed for experimental or other scientific use, the place where it is killed is a designated establishment and the method employed is not one appropriate to the animal under Schedule 1 to this Act."
"(4) In determining whether and on what terms to grant a project licence the Secretary of State shall weigh the likely adverse effects on the animals concerned against the benefit likely to accrue as a result of the programme to be specified in the licence. (5) The Secretary of State shall not grant a project licence unless he is satisfied - (a) that the purpose of the programme to be specified in the licence cannot be achieved satisfactorily by any other reasonably practicable method not entailing the use of protected animals; and (b) that the regulated procedures to be used are those which use the minimum number of animals, involve animals with the lowest degree of neurophysiological sensitivity, cause the least pain, suffering, distress or lasting harm, and are most likely to produce satisfactory results."
"If it appears to any person specified in a certificate pursuant to subsection (5) above that the health or welfare of any such animal as is mentioned in that subsection gives rise to concern he shall - (a) notify the person holding a personal licence who is in charge of the animal; or (b) if there is no such person or it is not practicable to notify him, take steps to ensure that the animal is cared for and, if it is necessary for it to be killed, that it is killed by a method which is appropriate under Schedule 1 to this Act or approved by the Secretary of State."
"(a) a condition to the effect that the holder shall take precautions to prevent or reduce to the minimum consistent with the purposes of the authorised procedures any pain, distress or discomfort to the animals to which those procedures may be applied; and (b) an inviolable termination condition, that is to say, a condition specifying circumstances in which a protected animal which is being or has been subjected to a regulated procedure must in every case be immediately killed by a method appropriate to the animal under Schedule 1 to this Act or by such other method as may be authorised by the licence."
"(1) Where a protected animal - (a) has been subjected to a series of regulated procedures for a particular purpose; and (b) at the conclusion of the series is suffering or likely to suffer adverse effects, the person who applied those procedures, or the last of them, shall cause the animal to be immediately killed by a method appropriate to the animal under Schedule 1 ..."
"(1) The Secretary of State shall publish information to serve as guidance with respect to the manner in which he proposes to exercise his power to grant licences and certificates under this Act and with respect to the conditions which he proposes to include in such licences and certificates. (2) The Secretary of State shall issue codes of practice as to the care of protected animals and their use for regulated procedures and may approve such codes issued by other persons. (3) The Secretary of State shall consult the Animal Procedures Committee before publishing or altering any information under subsection (1) above or issuing, approving, altering or approving any alteration in any code issued or approved under subsection (2) above."
"... such information as he considers appropriate with respect to the use of protected animals in the previous year for experimental or other scientific purposes."
"5.40 The severity limit for each protocol is determined by the upper limit of the expected adverse effects that may be encountered by a protected animal, taking into account the measures specified in the licence for avoiding and controlling adverse effects. It represents the worst potential outcome for any animal subjected to the protocol, even if it may only be experienced by a small number of the animals to be used. 5.41 In assessing the severity limit of a protocol, account should be taken of the effect of all the procedures (whether regulated or not) applied to each animal or group of animals; the nature and extent of the likely adverse effects; the action taken to mitigate those effects; and the humane endpoints to be applied. 5.42 The severity limits in the protocols in the licence are categorised as follows. • Unclassified Protocols performed entirely under general anaesthesia, from which the animal does not recover consciousness. This includes the preparation and use of decerebrated animals. • Mild Protocols that, at worst, give rise to slight or transitory minor adverse effects. Examples include: small infrequent blood samples; skin irritation tests with substances expected to be non-irritant or only mildly irritant; minor surgical procedures under anaesthesia such as small superficial tissue biopsies or cannulation of peripheral blood vessels. However, if used in combination or repeated in the same animal, the cumulative severity may be increased beyond mild. Protocols may also be regarded as mild if they have the potential to caused greater suffering but contain effective safeguards to initiate effective symptomatic or specific treatment or terminate the protocol before the animal shows more than minor adverse effects. • Moderate Protocols regarded as moderate include toxicity tests (which do not involve lethal endpoints) and many surgical procedure (provided that suffering is controlled and minimised by effective post-operative analgesia and care). Protocols that have the potential to cause greater suffering but include controls which minimise severity, or terminate the protocol before the animal shows more than moderate adverse effects, may also be classed within the moderate severity limit. • Substantial Protocols that may result in a major departure from the animals state of health or well-being. These include: acute toxicity procedures where significant morbidity or death is an endpoint; some efficacy tests of anti-microbial agents and vaccines; major surgery; and some models of disease, where welfare may be seriously compromised. If it is expected that even one animal would suffer substantial effects, the procedure would merit a 'substantial' severity limit. The Secretary of State will not licence any procedure likely to cause sever pain or distress that cannot be alleviated [Section 10(2A)]. THE SEVERITY CONDITION 5.43 Licence holders are required by conditions in both project and personal licences to minimise any pain, suffering, distress or lasting harm. They should approach the limit of severity which has been authorised only when absolutely necessary to meet the specified objective [Sections 10(2) and 5(5)]. 5.44 If it seems likely that the severity limit of a procedure has or may be exceeded, the project licence holder, or the deputy project licence holder, must contact the Home Office. Provided the project licence holder can show sufficient justification, the Secretary of State may temporarily authorise a higher severity limit for a period of up to 14 days to allow the balance of likely benefit and likely cost to be reviewed and amendment to the project licence to be considered. 5.45 The project licence condition will be regarded as breached if the Home Office is not notified promptly by the project licence holder (or deputy) when a protected animal has, as the result of the regulated procedures performed, suffered (or is likely to suffer) more than is authorised by the severity limit. It will also be regarded as breached if the endpoints applied resulted in more suffering than was necessary to achieve the specific objectives. 5.46 The condition may be considered to have not been breached if the suffering arose for an unforeseeable, extraneous (that is, a problem unrelated to the regulated procedures), providing adequate and effective steps have been taken promptly to alleviate the suffering. THE OVERALL SEVERITY BAND OF A PROJECT 5.47 The assessment of the overall severity of a project will reflect the cumulative effect of each procedure. This assessment is used by the Secretary of State to weigh the likely adverse effects on all the animals to be used against the benefits likely to accrue, as required by Section 5(4) of the Act. 5.48 The assessment of the severity band for the project as a whole reflects the number of animals used on each protocol and the actual suffering likely to be caused as a result. It is based on the overall level of cumulative suffering to be experienced by each animal, not just the single worst possible case. It takes into account the proportion of animals expected to reach the severity limit of the protocol and the duration of the exposure to that severity limit, the nature and intensity of the adverse effects, and the actions to be taken to relieve the suffering. 5.49 The assessments of severity (of individual protocols or the project as a whole) should be reviewed and revised as necessary during the lifetime of a project."
"4.10 Many procedures are likely to be assessed as moderate. This could include much of the screening and development of potential pharmaceutical agents; toxicity tests avoiding lethal endpoints; and most surgical procedures, provided that suffering can be controlled by reliable post-operative analgesia and care. 4.11 Procedures will be regarded as being of substantial severity if they result in a major departure from the animal's usual state of health or well-being. These are likely to include acute toxicity procedures where significant morbidity or death is an endpoint; some efficacy tests of antimicrobial agents and vaccines; some models of disease and major surgery where significant post-operative suffering may result. If it were expected that a single animal would suffer substantial effects, the procedure would warrant a severity limit of 'substantial'."
"Neither the severity limit nor the wording used in the protocols to describe adverse effects is intended to convey to the public the severity of the protocols. They are a means of communication between researchers familiar with the particular work and the inspectors who have to judge whether the experiments performed accord with the licence authorities and controls."
"The Home Secretary will be empowered to issue guidelines describing in more detail the factors he will take into account in reaching a decision whether or not to issue a project licence and how the categories of severity are to be defined and applied. This will be a significant new step in explaining to licence applicants, licensees and members to the general public the way in which the controls are intended to work."
"4.17 Six of the protocols have been assigned moderate severity limits. 4.18 Five of the six moderate protocols were thus classified on the basis • that the intention is by performing surgery to produce specific and precise brain lesions that require pain relief; • that an appropriate period of special care immediately post-operatively will be provided; • that although the purpose is to model aspects of human brain disorders, the animals used do not display the persistent, severe, disabling signs seen in human clinical practice; • that the neurological defects are expected to be transient and thereafter only demonstrable on formal testing; or any persisting, stable neurological deficit will not prevent animals undertaking their normal activities of daily living; • and, furthermore, that should more severe adverse effects be seen the problems will be promptly identified and remedied."
" Stroke Studies 5.C.15 The stroke studies mentioned in the BUAV report use a model based upon occlusion of one middle cerebral artery. The project licence also makes provision for the occlusion of other blood vessels. 5.C.16 In the immediate post-operative period the animals are cared for incubator and hand-fed as required. This is generally required for several days post-operatively; all but two animals have been recovered quickly enough to be returned to their home cage in two to three days. 5.C.17. There have been two deaths using this model within six hours of surgery, and a further two deaths several weeks post-surgery from cerebral haemorrhages. 5.C.18 This procedure results in impaired use of one hand or arm, affecting voluntary use rather than automatic movements, but without evident weakness or paralysis requiring the provision of special care because the animals cannot undertake their normal activities of daily living. During the course of this review animals with established lesions were observed and appeared at first sight to be almost normal. 5.C.19 Transient, one-sided spatial neglect demonstrable on formal testing can be produced but usually resolves within eight to ten weeks. Again, in the laboratory setting, this does not require that additional care is provided. ... Adverse Effects Encountered 5.C.39 Records confirm that since the project licence was granted in 1998, approximately four percent of the animals used for this project have died or have been euthanased on welfare grounds before completing the study protocols. 5.C.40 The stroke produced by the unilateral occlusion of the middle cerebral artery has typically required that animals be kept in an incubator for several days after surgery; the average time in an incubator has been 3.2 days. During this time animals had reduced use of one hand and arm, and a tendency to rotate and/or turn the head to one side. Recovery was relatively rapid and the animals stabilised with reduced use of one hand and arm as described above. 5.C.41 In other studies the cognitive dysfunction (principally impairment of certain types of conditional learning and visual discrimination) and any visuo-spatial neglect caused by damage to selective brain structures was only apparent on formal testing. 5.C.42 Rarely delayed brain disorders were seen three weeks or so after surgery. These are discussed above. 5.C.43. Excitotoxic lesions tended to lower the seizure threshold for twenty-four hours or so post-surgery. Some seizures (generally spinal jerks or Jacksonian rather than grand mal) did occur. These were controlled and managed by the administration of diazepam and placing the animal in dimly let, quiet surroundings to prevent disturbance. 5.C.44 Following the production of bilateral thalamic excitotoxic lesions two animals did not recover: one died whilst still under general anaesthesia and the other within twenty-four hours of surgery. The protocol was amended and the problem did not recur. 5.C.45 Animals with bilateral infero-temporal lesions tended to display behavioural changes analogous to those reported in macaques with the Kluver-Bucy syndrome. In the affected marmosets the condition was manifest as a combination of abnormal tameness, altered social behaviour, 'oral tendency', inappropriate sexual behaviour and an inability to distinguish between food and non-food objects. Although the abnormal tameness persisted, the other behavioural changes were transient and generally resolved within a few days, during which time the impact of the behavioural changes was managed by appropriate changes to the husbandry and care systems. One animal, however, had a persistent form of the condition and was humanely killed as it was not considered a suitable research subject. 5.C.46 Although animals' behaviour is altered, and supplementary care must be provided when the condition is first seen, the more socially disabling signs are transient and do not seem to distress the animals."
"Protocols that may result in a major departure from the animals state of health or well-being."
"The systemic administration of the neurotoxin MPTP to non-human primates produces the full-blown clinical condition as seen in human clinical practice although, contrary to the human experience, the clinical signs may improve rather than worsen with time. This model produces, even with treatment, persistent, severely disabling and distressing clinical signs (with rigidity, tremor, and paucity of spontaneous movements being the main hallmarks of the condition) requiring a prolonged period of intensive care and leaving residual neurological damage requiring high-dependence special-care thereafter. Although not generally believed to be a painful condition in the animal models (it is essentially painless in man) it is considered to cause distress in the affected animals."
"... the reference at the 4th bullet point of paragraph 5.42 of the Guidance to 'Protocols that may result in a major departure from the animal's usual state of health or well being' should be interpreted in that context: i.e. it is a higher order of pain, suffering, distress or lasting harm than is catered for by the Moderate severity limit."
"... should more severe adverse effects [than transient neurological defects or persisting defects which will not prevent animals undertaking their normal activities of daily living] be seen the problems will be promptly identified and remedied."
"It is the responsibility of the project licence holder to ensure adherence to the severity limits as shown in the listing of procedures/protocols (Section 19a) and observance of any other controls described in the procedure/protocol sheets (Section 19b). If these constraints appear to have been, or are likely to be, breached, the project licence holder shall ensure that the Secretary of State is notified as soon as possible."