Professor Martin Gore (Vice Chair)
Dr John Carr
Dr Martin Carrier
Dr Peter Coyle
Prof Ernest Gould
Dr Penny Hirsch
Dr Keith Howard
Prof David Lewis
Mr Robert Osborne
Dr Brian Robertson
Dr Peter Searle
Dr Michael Skinner
Dr Paul Logan
Mrs Diane Fox-Purday
Mrs Diane Tsavalos
Dr Androulla Gilliland
Dr Francesca Day
Dr David Brown
Dr Michael Paton
Prof Janet Bainbridge (Chair)
Dr Gary Burns
Dr Margaret Lacey
Dr Philip Minor
1. The Chair welcomed everyone to the twelfth meeting and suggested that given the discussion that agenda item 5 was likely to generate, agenda item 6, should be heard first.
2. The minutes were accepted as a true and accurate record of proceedings.
3. There were no matters arising.
4. The revision of The Guide to the Genetically Modified Organisms (Contained Use) Regulations 2000 or ‘The Brown Book’ has been delayed on account of a threat of legal action by the EC over improper implementation of the Contained Use directive. The HSE needs to address the points made and David Milliband, MP is dealing with the issue. As yet, there is no requirement for SACGM to become involved.
5. There have been a number of GM accidents involving the H5N1 vaccine strain. Although not very serious, the injured person (IP) experienced a disproportionate response upon reporting to the local A&E department. HSE is investigating and an early observation is that the company’s contact card is inadequate.
6. Dr Logan recounted his experiences as the appointed lead inspector into the two recent releases of FMDV at Pirbright. One of the knock-on effects of finding that the facilities and work procedures were not fit for purpose was that the competent authority (CA) had no choice other than to withdraw GM consents at the site. Work involving Morbilliviruses will be moved to a better laboratory. The CA is working very hard with the dutyholders to have consents reinstated. A question was raised about the implications for the proposed construction of a containment level 4 facility at Compton and planned avian influenza research. Dr Logan assured the committee that this would not be affected.
7. Dr Brown outlined the work activity that led to the accident in which a small volume of high titre culture was injected subcutaneously into the thumb of the IP.
8. The Chair directed the meeting to concentrate on the clinical picture and invited the views of the clinicians, Dr Coyle and Prof Lewis.
9. The main focus of discussion was on the unnatural route of delivery.
10. Members queried whether there were any data on the effects of delivering the wild type organism via this route. No wild type control was used.
11. The consensus was that the IP’s symptoms were typical of necrotising fasciitis.
12. The use of sharps was not indicated in the risk assessment and one member expressed surprise that this was not covered in the assessment. The committee were of the opinion that the severe reaction observed was unlikely to be the result of the genetic modification. The fact that all of the pigs injected subcutaneously with four different signature tagged mutants showed oedema at the injection sites indicates that the reaction was unlikely to have resulted from the random transposon insertion in the mutant. However, without carrying out further in vivo studies, members could only postulate that the wild-type organism would cause a similar reaction if subcutaneously injected into pigs.
13. The issue of whether it was likely that the bacteria had replicated following inoculation or if the reaction was due to the high levels of endotoxin was also discussed. The opinion, based on the pathology observed, was that it was likely that it had replicated in the thumb and the tissue damage observed was due to one or more of the bacterial toxins.
14. Finally, members commented that when any microorganism is inoculated by a novel or previously unexplored route there is a possibility that an unexpected reaction could occur, even when the organism is harmless via the natural exposure/ transmission route. Based on this advice, it may be necessary to amend risk assessments to consider the possibility of adverse reactions following accidental exposure to such pathogens. Where such a possibility exists, additional control measures need to be considered e.g. prohibiting the use of sharps or, if that is not possible, highlighting the risk of exposure through sharps injuries.
15. The Chair concluded that it was not possible to predict an organism’s pathogenesis when inoculation occurs via a novel route, which is likely to have been the cause of the IP’s injuries rather than it having been genetically modified.
16. Two members declared an interest as colleagues of the principal investigator (PI).
17. Dr Logan warned the Committee that decisions on levels of containment must not be taken lightly as they may have financially costly ramifications. He went on to outline the forthcoming presentation, pointing out that it was the work of the first and not the second PI that was of most relevance to the Committee. Parts of the programme have already been notified to the CA.
18. Major points for members to consider include:
19. In response to the Chair’s request for comments, one member pointed out that there are major occupational health considerations at the forefront of the programme and queried if the projects were being carried out sequentially. It was noted that some strands of work are to run concurrently.
20. The Chair introduced the two guest speakers who gave a detailed presentation outlining the proposed programme of work and inviting questions during the presentation. The PI explained the rationale behind the choice of the donor strains and described the benefits of reverse genetics.
21. The Chair thanked the speakers and pointed out that although the later stages of the programme are years away, the infrastructure needs to be of sufficient quality to enable a smooth transition. The programme therefore needs an indication from the CA that it is satisfied, in principle, with the proposal. The meeting was then opened for questions.
22. The Committee agreed that it was content with the proposed levels of containment and comfortable with the approaches taken. The Chair commented that this was only an outline proposal and the wording of the risk assessments will need to be considered carefully in order to influence public perceptions.
23. The Chair explained that this questionnaire originated from UK queries to the EU and it applies to SACGM/06/07/P3 – status and classification of herpes simplex virus strain 1716, which the German CA considers to be GM. This has raised wider issues in Europe and workers are interested in the UK’s two-system approach, i.e. Deliberate Release involving not many trials and Contained Use involving many trials. Although the EU has no views on how gene therapy should be treated.
24. One member expressed disappointment in the quality of the questionnaire which focuses on gene therapy and appears to view the two permissioning schemes as mutually exclusive. It may be that its authors are mistaken in their belief that all clinical trials involving GM are gene therapy. There are definite advantages of having the flexibility to be able to choose between DR and CU: the CU approach provides a richness of data that facilitates a DR application. The SACGM Compendium was written in the spirit of flexibility.
25. A review group on vaccines produced by reverse genetics is to start up early 2008.
26. The Royal Society is setting up a synthetic biology working group. HSE will argue that it should be regulated under CU. This will undoubtedly be a future issue for SACGM.
The Chair drew the meeting to a close, thanking everyone for their attendance and contributions.
