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Venomous Country (continued)

Ken Winkel: Certainly, that's true, although newborn mice for 24 hours are sensitive to the effects of the venom. So Struan's first experiments with the experimental anti-venom were in newborn mice. Perhaps John could tell us about the first proof of the efficacy of that product in those animals which then necessarily had to be taken to a primate model before a clinical trial.

John Pearn: I've been privileged to have some wonderful moments in my life. One of those occasions was in late 1980 or early 1981. I had a small toxinology laboratory in Brisbane and, at the time, Alan Coulter was helping us set up an ELISA for one particular snake (the rough-scaled snake, Tropidectus carinatus) that we were interested in assaying in Brisbane. I was in Melbourne for other reasons and I remember ringing Struan up and saying I'd like to talk about this. Struan said, 'Of course, John', and 'Would you come out tomorrow. We're doing the LD50s on the use of the model of newborn mice injected with the funnel web spider venom protected with our new emergent funnel web antivenom'.[63]

I remember visiting CSL the next day and going with Struan to his room where he had two plastic laboratory containers. They were green in colour, and full of wood shavings. In one, there were five little nude pink newborn mice, all dead. In the other, the shavings were moving as the newborn mice wriggled around in that box. I remember the words Struan said, 'This is a special day'. And it was one of the definitive experiments in the history of Australian toxinology - the first successful use of funnel web spider antivenom.

Now those sorts of experiment or LD50s are now not approved for animals in most parts of the world, though LD50 studies are a basic tool that toxinology is founded on. But at that time it was the normal assay for antivenom protection using whole animal models. And I recall that occasion as a very special moment in my life.

Ken Winkel: I guess the issue of the use of animals is very hotly debated today and I think Jim might have some particular comments on that issue.

Jim Angus: Firstly, we have come a long way and I think researchers in Australia today take a lot of comfort with the setting up of ethics committees and the serious way in which the state government officers patrol ethics. If we don't have the protection of the Government, and therefore the community, researchers couldn't do what we do today, and therefore couldn't do the critical science. We would otherwise be trying to work in an environment such as we see in England, and a lot of our research would have to be forced off-shore to places that don't have the ethics controls that we have. I think that would be a great shame because the quality of the research would not necessarily be at the high level that we sustain here.

So I am solemnly behind the ethics committees, but I do think in some instances they go too far. They get very strictly into the design of your experiment, and the numbers of animals, rather than really looking at the ethical issue of the application and the care of the animals, the use of anaesthetics and antibiotics etcetera. They tend to be more hooked on numbers.

So much so that when Struan first came to our group, we tried to get permission to set up the LD50 tests for some of the toxins that we had, which had never been through the mice LD50. Now in Victoria, to set up an LD50 you have to get express permission from the Minister and the Minister, of course, would refer back to an expert committee. And Struan wanted 16 mice in a particular LD50 test and was able to defend it with what he had done in the past at CSL. And do you know that after six months we were still prevented on statistical grounds from going ahead with this LD50. And we still, to this day, do not have permission to do those LD50 tests in a very controlled environment to look at a comparison of the toxicity of these venoms. I think we're the poorer for it. I understand all the issues about why LD50s in most instances shouldn't be allowed. But I still believe that we have got too much red tape in some areas.

As far as the teaching of people to use animals, it's dying. It's very hard today to find in a medical school, people with experience in handling animals in a practical sense. That's why we started a third year course in pharmacology in just teaching in vivo pharmacology so that we retain some expertise in Australia and can do some of these very important experiments on the way through to drug or antivenom development. It's terribly important that we have this resource.


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