Cutting edge: Bob Seamark

February 2, 2001

Having accidentally made a deadly disease more virulent, we went public with our research despite the inevitable furore.

Australia's unique landscapes and biodiversity stand threatened. Processes initiated just two centuries ago with European colonisation have led to the almost complete destruction of natural ecosystems and the extinction of many plants and native animals. Among the chief culprits are three introduced animals - the rabbit, fox and house mouse.

Management of such pests is a major challenge. The only practical, cost-effective prospect is to use bio-control agents such as myxoma virus and rabbit calicivirus. For most pests, however, there are very few agents that are lethal to the majority of animals and retain the species-specificity that environmental safety requires.

At the government-sponsored Cooperative Research Centre for the Biological Control of Pest Animals, we believe we may have an answer. Using biotechnology, we have shown it is possible to develop effective, non-lethal biological control agents that reduce the growth of pest populations through fertility control. What we have in mind are immunocontraceptive vaccines delivered in the wild via viruses. By judiciously choosing naturally occurring viruses that infect only the targeted pest animal and combining this with species-specific vaccine antigens, we can more than match the level of environmental safety required to satisfy Australia's revamped regulatory system.

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Researchers infected female mice with a benign mouse-specific virus, murine cytomegalovirus, or MCMV. This had been genetically modified to include a mouse gene that produces a female egg protein called ZP-3. Within three weeks, the mice generated an immune response to ZP-3 that rendered females sterile. We also needed to combat the agent's gradual loss of effectiveness. The myxoma virus killed more than 98 per cent of infected rabbits after its release in the 1950s, but in a few years it was killing only 50 per cent as surviving animals bred and passed on resistance genes.

Mice also have resistance genes, not only to MCMV but also to other viruses such as mousepox, a laboratory virus used to study disease resistance. It was during studies on how mousepox viruses might be modified to overcome resistance that we made the discovery that has caused such consternation.

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We found that if mousepox was modified to include a substance called interleukin-4, the virus could overwhelm resistance mechanisms, killing all infected mice. Furthermore, and much to our concern, we found that we were unable to protect them using normal vaccines. The spectre of scientists, inadvertently or deliberately, modifying human or livestock pathogens to create new disease organisms against which there was little defence demanded a response.

We chose total disclosure, publishing our results in an internationally respected journal and instigating a public awareness campaign. We knew the risks: raising the ire of some scientists and the public, causing our research sponsors concern and adding fuel to the already inflamed debate over genetically modified organisms. We argue that we were right, but only time will tell.

More recently, we have shown that a genetically weakened strain of modified mousepox allows mice to survive and show enhanced immune response. By revealing both sides of biotechnology, we expect our project to become a benchmark for regulatory protocols to assure the public of safety and transparency concerning the release of genetically modified organisms.

Bob Seamark is chief executive officer, Cooperative Research Centre for the Biological Control of Pest Animals in Canberra, Australia.

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