National Antivisection Society
Back inside the Institute of Neurology
16 January 2007
Last year an NAVS/ADI Field Officer worked for several months as an animal technician in the Medical Research Council’s Prion Unit in London, part of the Department of Neurodegenerative Disease and the Institute of Neurology.
The main focus of the Prion Unit is the Transmissible Spongiform Encephalopathies (TSEs), a group of diseases including mad cow disease (BSE) in cattle, scrapie in sheep and goats, and variant Creutzfeldt-Jakob Disease (vCJD) in humans.
TSE diseases are caused by prions (proteins rather than organisms) and cause a change in naturally occurring proteins into a “misfolded” variant, which accumulates in the central nervous system and lymphoid organs[1].
TSE diseases are highly resistant to conventional disinfection methods[2]. The risk of transmitting prion disease between patients has prompted a number of scientific reports on this subject[3-5]. The absence of effective treatment and the fatal nature of the prion diseases should demand extreme caution by researchers working with prions[6], particularly with sterilsation.
Our Field Officer noted that the lab’s rules require that everything coming from the experimental labs is contaminated and so must be sterilised – generally by autoclave. However this rule is often broken in the Prion Unit, and the sterilisation equipment was frequently out of order.
Animal suffering
The Home Office licences experiments on animals in four categories of severity – ‘unclassified’, ‘mild’, ‘moderate’ and ‘substantial’. Substantial is described as “involving more than a transitory major departure from the animal’s usual state of health or well-being” and covers e.g. “some models of disease, where welfare may be seriously compromised.”
Prion diseases lead to severe symptoms and death. Our Field Officer learned that the project carried a ‘substantial’ licence allowing the animals to endure an extended period of suffering before being killed. He was told that animals can be left until they lose 25% of body weight, or are unable to eat or drink.
As we have reported in the past, the high level of surplus animals killed in laboratories means many animals die than are recorded. This also reinforces the culture within laboratories that the animals are simply disposable. Over a period of 15 weeks 1,729 mice were killed because they were not needed.
Unreliable, Unnecessary
There are key differences between humans and mice when it comes to prion disease. Infected mice die within months, while the incubation time for CJD in humans can be decades[1]. Furthermore, mice do not naturally develop prion disease, they must be artificially infected – usually by injection into the brain. By contrast prion disease such as BSE transmits to humans through ingestion of infected meat[1,9].
Researchers successfully infected mice with prion disease for the first time in 1961, by injecting infected brain substance into their brains. The same method is still commonly used, and preferred, as it results in the rapid onset of disease[10]. Yet today, alternatives are available for most areas of prion research[10].
Experiments in the Prion Unit
Decontamination methods
Researchers inserted prion-covered steel wires into the brains of hundreds of mice to compare different decontamination methods for surgical instruments[11].
The metal wires were contaminated with prions from mice terminally ill with prion disease, with some decontaminated by different methods. Genetically modified (GM) mice were used but normal mice were used as well in order to compare results with the GM mice.
The tests were also repetition of earlier work. Numerous studies of prion decontamination methods have already been conducted, including. studies on both hamsters[12] and mice[13].
The animals suffered the symptoms of the disease, the pain and distress of the implants, and some were simply found dead in their cages.
Yet these researchers were not only aware of an alternative, two of them had actually co-authored a paper on a highly sensitive cell-based method for measuring prion infectivity[14] – more sensitive than the animal tests.
An alternative to sterilising surgical instruments would be to develop better single-use instruments. This would not only spare animals from suffering, but would also be safer. The failure of a laboratory mouse to develop scrapie under such laboratory conditions is not guarantee of the sterilisation method.
Prion structure
In one experiment, researchers injected GM mice with human prions to trigger an immune system response[15] so that the structure of the prion proteins could be studied. Brains from healthy as well as from terminally scrapie-ill mice were used. Despite the considerable suffering caused, the paper published by these researchers did not even discuss the potential application of their findings for the benefit of human vCJD patients.
Similar research has been carried out for almost 10 years[16].
Yet a review of this field in 1999 noted that non-animal methods for studying the mechanisms of prion conversion were already available[10].
Crippled mutant mice and scrapie
Another study to examine the transport of prions in the nervous system in connection with the onset of scrapie[17], employed mice carrying a mutation affecting the transport of nerve signals, as compared with other mice.
The researchers injected scrapie prions into mice, killed them, liquidated their brains and then injected the mixture into the brains or abdomens of other mice.
All mice injected with prions developed scrapie and were killed. No differences in incubation times were found between the different mouse strains or between the two injection methods.
Yet cell-based studies, using rodent brain cells, had already been used to examine this area of prion research[18]. In this instance the experimenters claimed that the cell-based studies didn’t provide clear answers about the role of the pathways – but neither did their study.
References:
1. Voet, D. & Voet J.G. (2004) Biochemistry 3rd Ed. John Wiley & Sons, Inc.
2. Rutala, W.A. & Weber D.J. (2001) Clinical Infectious Diseases 32: 1348-1356.
3. McDonnell, G. & Burke, P. (2003) Clinical Infectious Diseases 36: 1152-1154.
4. Fichet, G. et al. (2004) Lancet 364: 521-526.
5. Hirsch, N. et al. (2005) Anaesthesia 60: 664-667.
6. Richmond, J.Y. et al. (2003) ILAR Journal 44: 20-27.
7. Health and Safety Executive (2006). http://hse.gov.uk/biosafety/law.htm. Accessed 070906.
8. Approved List of biological agents (2004) http://hse.gov.uk/pubns/misc208.pdf. Accessed 070906.
9. WHO (2002). Fact sheet no 180, November http://www.who.int/mediacentre/factsheets/fs180/en/index.html. Accessed 070906.
10. Jenkins, E.S. & Combes, R.D. (1999) ATLA 27 (supplement 1): 827-838.
11. Jackson, G.S. et al. (2005) Journal of General Virology 86: 869-878
12. Yan, Z-X. et al. (2004) Infection Control and Hospital Epidemiology 25: 280- 283.
13. Flechsig, E. et al. (2001) Molecular Medicine 7: 679-684.
14. Klöhn, P-C. et al. (2003) PNAS 100: 11666-11671.
15. Khalili-Shirazi, A. et al. (2005) Journal of General Virology 86: 2635–2644.
16. Hill, A.F. et al. (1997) Nature 389: 448-450.
17. Hafezparast, M. et al. (2005) Biochemical and Biophysical Research Communications 326: 18-22.
18. Moya, K.L. et al. (2004) J. Neurochem. 88: 155–160.
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