Minutes of Meetings - December 1999

Animal Procedures Committee  APC (99) 8th Meeting
Minutes of the meeting held on 8 December 1999

1. Apologies for absence

1.1 Apologies from Dr Suckling and from Professors Atterwill, Broom, and Holland.

1.2 The Chairman noted that Dr Suckling was shortly to leave the Committee, having completed the maximum 8-year term as a member. He expressed his own and the Committee's thanks for the considerable contribution Dr Suckling had made over that time.

2. Minutes of the previous meeting (10 November)

2.1 The minutes were agreed, subject to changes to paras 1.1, 3.7, 3.8, 3.12 and 5.2.

3. Matters arising

3.1 Ferrets and gerbils (para 3.2) The Home Office ABCU were appraising the responses to the consultation exercise and would be submitting a revised draft to the Minister.

3.2 Tobacco applications (para 3.11) The Minister had replied to the Chairman (see INF(99)46).

3.3 Pigs as xenotransplantation source animals (para 3.14) The Secretary had written to Home Office ABCU (see INF(99)43).

3.4 Harlan-Hillcrest (para 3.16) The Inspectorate had completed their report and passed it to Home Office ABCU who would submit it to the Minister.

3.5 World Trade Organisation talks (para 4) The Chairman had written to the Home Secretary, who had replied confirming that details of the Committee's proposals had been passed to the Department of Trade and the Ministry of Agriculture, Fisheries and Food (see INF(99)45). The Chairman would write again to the Home Secretary to ask about the outcome. Action: Chairman

3.6 Cat experiments at Newcastle University Medical School (para 5.2) The Chief Inspector confirmed that the programme of work on cats had been carried out under licence at Newcastle University Medical School.

3.7 Accident cover for members of the APC (para 5.3) The Secretariat had consulted the Home Office Health & Safety section and been advised to refer the matter to the Department's legal advisers. They had done this and awaited the outcome. Action: Secretariat

4. Primate applications - APC(99)44, 45, 46

4.1 The Committee had before it two applications for the use of primates in substantial procedures connected with work on Parkinson's disease (PD) and related diseases. It had originally considered this programme of work at its June 1999 meeting, when it had been formulated as a single licence application. The Committee had at that time recommended that Ministers turn the application down, and they had done that.

4.2 The applicants had resubmitted their request to the Home Office. It now appeared as two separate applications, PPL 70/4986 (paper APC(99)44) and PPL 70/4995 (paper APC(99)45). The Secretariat had forwarded these papers to the primate sub-Committee, who had formulated some questions about them which appeared as paper APC(99)46. The applicants attended the meeting in person to assist the Committee.

4.3 Before discussion began a member asked that the minutes record what might be perceived as his an interest as a professor at the same institution, albeit in a different department to the one connected with the primate applications.

4.4 Applicants' responses to the comments in APC(99)46 applying to both applications

4.4.1 The applicants confirmed (point 1 in APC(99)46) that animals would be killed by lethal injection before decapitation.

4.4.2 Statistical advice (point 2) had been taken throughout the 15-year research period. New advice was taken when statistical methods and techniques had been refined or where unexpected results occurred, to ensure the analysis was correct.

4.4.3 Hemi-Parkinsonism was not considered to be a better alternative model for the experiment (point 3). The sensory deficit that would occur could lead to bizarre behaviour and affect the responses of the animals. For anatomical reasons there would inevitably be some unpredictable level of damage on the untreated side of the brain.

4.4.4 Marmosets were used in studies of PD (point 4), even though they would not develop Lewy bodies (LB) which are a pathological marker for PD. They would lose dopamine cells, and suffer damage to critical mitochondrial enzymes, also recognised end results of PD.

4.4.5 The applicants said that there had been no cases of anaemia in their animals (point 5). Taking blood samples could not in itself prevent animals becoming anaemic, so they ensured that the dietary intake of the animals was regularly checked and that the named vet was consulted about appropriate iron supplements.

4.4.6 The terms sporadic and idiopathic PD (point 6) were used to differentiate the common occurrences of PD with rare genetic, toxic or viral causes.

4.4.7 The applicants confirmed (point 7) that the overall numbers of animals to be used over the lifetime of both projects had been based on the maximum numbers they would expect to use. In reality, they did not anticipate using more than 50 or 60 animals per year. They suggested that they might be able to reduce the number of animals further if they were allowed to submit individual animals to more than one procedure. However, such action was not permitted under the 1986 Act.

4.4.8 In later discussion, the Home Office Inspectorate confirmed that animals must not be submitted to more than one procedure of substantial severity. Welfare questions aside, there was doubt about whether re-using an animal which had been subjected to an earlier experiment would provide reliable or worthwhile results.

4.5 Applicants' responses to other issues applying to both applications

4.5.1 The applicants confirmed that marmosets were the preferred primate subject, even where repeated doses of MPTP would need to be administered. Their size was crucial. Marmosets were small non-feral laboratory bred primates and avoided the need to use larger primates. Every care was taken to ensure that their welfare concerns were met.

4.5.2 Members expressed concern over the compulsive climbing behaviour of marmosets that had been recorded in the first 8 weeks after MPTP treatment. The applicants confirmed that this was not unique to the marmoset and may indicate exaggerated stereotypical behaviour.

4.5.3 Steps had been taken to reduce the impulse to climb by using perspex cages and removing the means to climb. Where this had been done animals seemed content and tended to rest. However, it remained unclear whether the withdrawal of a climbing environment caused the animals distress because their climbing urges had been repressed.

4.6 Applicants' responses to the comments on application PPL 70/4986 in paper APC(99)46

4.6.1 (points 1 and 2) The applicants explained that it was difficult to prioritise the aims and objectives of their PD work as between probing causes and investigating the side-effects of treatment. Patients were either new to PD and wanted to stop or slow the progression of the illness, or were established sufferers who tended to be worried about side effects. Each group had different priorities and needs.

4.6.2 The application would involve a pilot study to develop a model for 'Parkinson's Plus, a more serious form of the disease. This would require a group of 12 animals to be treated variously with MPTP, 3 Nitropropionic acid, and with both (4 animals in each case). Dr Langley later drew attention to the need to clarify why it was necessary to test animals with MPTP, when animals in the laboratory were already being tested with this substance and data from these tests could be provided.

4.6.3 The applicants confirmed that their reference to introducing new methodologies (point 3) meant that they would review techniques and procedures during the course of the licence. Any substantial changes would be referred to the Home Office Inspectorate.

4.6.4 (point 4) Drugs would be tested that affected other neuronal receptors (e.g. GABA, 5HT etc), even though changes in MPTP-treated marmoset occur only in the brain's dopamine systems. This was because neurones do not work in isolation, and whilst the researcher would not get a pathological change there would be a biochemical change - giving the opportunity to manipulate the output of the brain and control motor function through other receptor systems.

4.6.5 (point 5) Animals would not lose their blink reflex. However, it had been noted that following MPTP treatment the blink reflex to external stimulus was different.

4.6.6 (point 6) The applicants confirmed that there was no intention to use anti-Parkinsonian drugs as part of the research. This had been included in the application in the event that a problem occurred where it would be in the animal's best interests to administer the drugs.

4.6.7 (point 7) The amount of blood to be sampled was correct. Blood samples were needed for two different reasons. The first was on-going investigations into the effects of MPTP, looking to improve aftercare, and the second was a theoretical maximum for blood sampling to check test blood and was a one-off procedure. Veterinary advice had been given in both instances.

4.6.8 (point 8) Brain implants would be in place no more than 28 days.

4.6.9 (point 9) The application was for academic research only. The applicants did not screen drugs and it was not their intention to do so.

4.7 Applicants' responses to the comments on application PPL 70/4995 in paper APC(99)46

4.7.1 (point 1) The applicant holds a personal license.

4.7.2 (point 2) The applicant was satisfied that their work on viral vectors in rodents had now reached the stage where it was appropriate to move up to the primate (marmoset) model. They did not propose any experiments on primates which had not already been carried out on rats.

4.7.3 (point 3) It was proposed that anti-Parkinsonian drugs would be given to the viral vector study animals. These would act as probes which may cause a reaction on one side of the brain that may otherwise have been overlooked.

4.7.4 (point 4) This application involved plans to make surgical lesions in the brains of siome of the animals. The applicant said that the aim was it was important to try to identify a precise lesion site within the brain to guarantee improvement in Parkinsonian symptoms. Scientifically, a failure could give as much important information as a success. The applicant hoped that the research would lead to an explanation of why lesions work and that this would enable them to advise surgeons.

4.8 Applicants' responses to other issues raised:

4.8.1 The applicants confirmed that the lesion work would be for one year only and a maximum of 20 marmosets would be used. The results would be published. The co-ordinates stated in the application had been determined from a study which had a 90% hit rate.

4.8.2 The applicants explained that they were unable to get data from the United States (US) on lesion work for human patients. Most of the patients were still alive and there was no system in place to ensure that the brains of successfully treated patients be investigated after their deaths.

4.9 Recommendations

4.9.1 PPL 70/4986 Most members, but not all, were content for the Chairman to write to the Minister advising that the application be approved, without conditions, subject to clarification about the need to test 4 additional animals with MPTP (in the combined lesion pilot), as opposed to using data from other MPTP treated animals. Action: Secretariat

4.9.2 PPL 70/4995 Most members, but not all, were content for the Chairman to write to the Minister advising that the application be approved, but repeating the Committee's concerns about climbing behaviour, the recommendation for a notification condition in the licence in relation to upgrading the work on rats to primates, and confirming the Committee's understanding that the pilot lesion work would be for one year only and involve a maximum of 20 primates.  Action: Secretariat

4.9.3 The Committee agreed to revisit the general issue of re-use of animals at a later date.

5. Format of the 1999 annual report - APC(99)47

5.1 The Secretariat was considering the format of the 1999 annual report. A draft annual report would be prepared for the February meeting, with the intention of the final report being published April 2000.  Action: Secretariat

5.2 Members agreed that the report should be written in simple English, and were not averse to pictures being used, provided that they had the approval of the Committee.

5.3 Members agreed that the inclusion of various Home Office activities (referred to in para 7) might not be directly relevant to the APC. But this sort of information had proved very useful to a number of organisations and it might be desirable to keep it in the report, perhaps as appendices.

6. Follow-up of the review of the Act - APC(99)48

6.1 The Secretariat would report what progress had been made in connection with the review of the Act to the Committee at the February meeting, and members were invited to submit any comments for inclusion in this paper. A draft work-plan would be published on the web in January 2000.  Action: Secretariat

6.2 Dr Purchase drew the Committee's attention to a letter he had written to the Chairman concerning the work of an Expert Group which had been formed to consider ways in which the administrative burden and general bureaucracy created by the 1986 Act might be simplified (INF(99)47). The Chairman noted the existence of the group and confirmed that the Committee would be interested to hear its findings.

7. Animal procedures in Northern Ireland

7.1 Mr Collins said that Northern Ireland is subject to the Animals (Scientific Procedures) Act 1986 in the same way as the rest of the UK. But licences are issued via the NI Department of Health (DHSSNI), on behalf of the (newly) devolved administration.

7.2 DHSSNI have two part-time inspectors, whose work covers 14 designated establishments, 422 personal licensees and 192 projects. The 1998 statistics showed that 15,711 procedures had been carried out in 1998, with 14,929 animals used for the first time. Any non-compliance was reported to their Minister and APC (this occurs perhaps -2 times per year). DHSSNI inspectors receive regular updates and ensure consistency with their UK counterparts by regularly attending Home Office Inspectorate meetings. Northern Ireland also has its own independent training group, providing training modules 1-3 and 5. The Ethical Review Process works well and operates in the same manner as the UK.

7.2 The Chairman thanked Mr Collins. He suggested that the APC might hold a meeting in Northern Ireland in the future and make visits under his guidance, in order to compare work and conditions.

8. Secretariat

8.1 The Secretariat were making arrangements for the planned APC meeting, and associated visits, in Edinburgh in February. It would help them if members made their availability known. Attendance at the visits was not compulsory.

8.2 The Secretariat would prepare a paper outlining the next year's visit plan. In addition to the proposed venues they were also asked to consider visits to the establishments housing the primate and tobacco applications which had been discussed by the Committee. Action: Secretariat

8.3 The Secretariat would write to all members seeking availability dates for the next few months, and their confirmation of whether they would like to receive information and meeting papers electronically (where possible) rather than a hard copy. Action: Secretariat

8.4 The Committee agreed that forthcoming agendas for meetings (not associated papers) could be posted on the web-site, provided that members had received their own copies first; and for security reasons, that dates and times of meetings and any sensitive names were removed.

8.5 The Secretariat confirmed that to ensure best practice, future meetings of the sub-committees and working groups would be kept to morning or afternoon slots only. Only in exceptional circumstances would day-long meetings, other than the monthly Committee meetings, be arranged.

9. Any other business

9.1 The Miscellaneous working group meeting planned for 16 December had been cancelled and would be rearranged for January 2000.  Action: Secretariat

9.2 Mr Evans circulated the Home Office's revision of its core Guidance on the Operation of the 1986 Act . The closing date for responses was 11 February 2000. He hoped that the Committee would have the opportunity to consider the document over the next few weeks, with a view to discussing it in more detail and formulating a response at their February meeting.

9.3 Professor Flecknell asked the Secretariat to provide clarification from the Home Office on the copyright status of the Act and guidance notes.  Action: Secretariat

9.4 The Home Office ABCU confirmed that an article that had appeared in The Mirror on 24 November had been referred to the Inspectorate for comment.

9.5 Mr Ward agreed to forward an article about defence establishment work, reported in The Mirror, involving goats in underwater experiments, and to write to the Chief Inspector.  Action: Mr Ward

9.6 Mr Turner asked if the Secretariat could issue advice to members on how to handle questions from members of the public, when attending meetings. Action: Secretariat

9.7 Mr McCracken raised a matter concerning the work of the Secretariat. The Chairman and members agreed that it was inappropriate to air such issues at a Committee meeting. Mr McCracken should if he wished to do so pursue the point with the Chairman outside the meeting.

9.8 Mr Gregory asked if the Committee would consider discussing whether or not the practise of manual surgery skills be allowed on animals. He mentioned the recent cases concerning children's heart operations in Bristol, where surgeons had stated that higher mortalities should be expected when performing novel techniques and procedures, as they were on a learning curve.

9.9 Mr Baker reported that it would be difficult for the Openness working group to meet its February deadline and that they may possibly miss the opportunity to feed in comments to the Freedom of Information Bill, as they had only just been informed about Cabinet Office handling issues for consultation papers. The Secretariat confirmed that they had only just received this guidance, and that it was a guideline only. They would consult with members of the working group and come to a view. Action: Secretariat

10. Next meeting

February 9, 10.30, venue to be confirmed.

• Minutes of Meetings
• Reports and Publications
• Consultation Letters
• Press Releases

• Animals (Scientific Procedures) Act 1986 (available on the Home Office website)

[Copyright Statement] [Complaints Procedure]