IAH scientist wins award for application of techniques that require fewer experimental animals for research into vaccines against Salmonella and E. coli in farm animals
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Mark Stevens on right receiving 3Rs award from Attila von Hanko President Intervet Japan 24 Aug 07 |
Professor Mark Stevens of the Institute for Animal Health’s Compton Laboratory has been awarded the 2007 Intervet Dieter Lütticken Award for his work on the reduction, refinement, and replacement (the 3Rs) of animals in research on bacteria that cause gastroenteritis in farm animals and people.
Professor Stevens and colleagues are identifying what it is that makes some types of Salmonella and E. coli cause gastroenteritis in animals and people. This research will identify targets within the bacteria for development of treatments against them. Surgical techniques developed within the Institute for Animal Health also speed up the identification of bacterial factors that play a role in the production of diarrhoea and enable new treatments to be tested using far fewer animals than previously.
Prof. Stevens said “By implementing novel methods
throughout our portfolio of research we believe that we have contributed
significantly to the development of veterinary medicines with minimal use of
animals in our experiments.”
The award recognises the progress in the 3Rs made by Mark Stevens not only with his colleagues in the Institute for Animal Health, but also with collaborators Professors Duncan Maskell (University of Cambridge), Ian Charles (University College London), and Gad Frankel (Imperial College, University of London).
He was presented with his award on Friday August 24 in Tokyo, during the 6th World Congress on Alternatives and Animal Use in the Life Sciences. (http://www.ech.co.jp/wc6/)
* For further information see below and/or contact Dr Dave Cavanagh, Press Officer, Institute for Animal Health:
* mobile (anytime) +44 (0)7789 941568.
* Office: 01635 577241
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The Dieter Lutticken Award for application of the the 3R's (reduction, refinement, and replacement) for the development and production of veterinary medicinal products
This international award, made by Intervet International, developer and producer of veterinary products, was established in 2004. It is given to scientists or public institutions that have delivered excellent contributions to the 3R's for the development and production of veterinary medicinal products. The award is named after Dr. Dieter Lütticken, a committed researcher who guided and shaped Intervet’s R&D for more than a quarter of a century. Dieter Lütticken retired in June 2003 from his position as Vice President and Intervet's Head of R&D. Further information on the award can be found at http://www.intervet.com/news/2007-06-22-intervet-dieter-luetticken-award-2008.asp
The three approaches that have led to a reduction in the number of animals used
In one approach (signature-tagged transposon mutagenesis) Mark Stevens and colleagues identified over 100 components of E. coli and over 200 components of Salmonella that enable the bacteria to colonise animals. This was done by making hundreds of mutants of the bacteria in the laboratory. Using old techniques it would have required the use of at least one animal to identify each component. Using modern (molecular biological) techniques, a mixture of 95 bacterial mutants can be examined using a single animal. Prof. Stevens is now using another molecular technique (transposon-mediated differential hybridisation), developed by collaborators Prof. Duncan Maskell (University of Cambridge) and Prof. Ian Charles (University College London), which enables at least 500 mutants to be analysed in a just one animal.
Figure 1. Hundreds of mutant bacteria are made in the laboratory. In one approach, a mixture of 95 of these mutant bacteria are inoculated into one animal. Those mutants that grow well are excreted and are identified. Those that do not grow well – because the mutation process had damaged a bacterial protein needed for growth in the animal (leading to disease) – are not excreted. By comparing the genes of the mutants that went into the animal with those that came out, it is possible to identify the proteins that were responsible for enabling the bacteria to cause disease. The objective is, with this knowledge, to then test whether any of these proteins could form the basis of a vaccine against E. coli.
In a second approach, anaesthetised animals are surgically operated on such that at least 12 different bacteria or disease control treatments can be studied in triplicate in one animal for their impact on invasion of the gut lining and the production of diarrhoeal symptoms.
Thirdly, in collaboration with Prof. Gad Frankel (Imperial College, University of London), researchers have been able to keep pieces of gut tissue alive in dishes in the laboratory for long enough to study how gut pathogens adhere to the tissue and invade or cause damage. In this way the researchers have been able to make use of animals that were killed for food reasons, humane reasons or at the end of unrelated experiments, thereby further reducing the number of animals produced for research.
Figure 2. Collaborative studies with Prof. Gad Frankel (Imperial College, University of London) have recently led to the keeping alive of pieces of gut tissue in Petri dishes. This permits studies of the interaction of the bacteria with cells at the gut surface. The pictures show cells infected with Escherichia coli O157. Top picture: visualization by immunofluorescence. Bottom picture: visualization by scanning electron microscopy