Countless mice and rats kick the bucket during the mandatory quality checks of produced vaccines. However, there are alternatives that can take place completely inside test tubes. 'If mice were monkeys, all hell would break loose.'

You never get used to seeing a mouse die of tetanus, says Prof. Dr. Coenraad Hendriksen, Professor in Alternatives for Animal testing at the Utrecht University and researcher for the National Institute of Public Health and the Environment (RIVM). Mice that have been injected with tetanus suffer visibly painful spastic cramps during their final hours. 'It's not a pretty sight. Most researchers in the laboratory think these tests are nasty and wouldn't mind losing them.'
The problem is that these mice are dying for a higher purpose, namely the production and testing of vaccines and hormone preparations. They are sacrificed for combating diseases that kill people and (agricultural) animals. Animal testing with this purpose is undisputed. Last year 20 percent of Dutch testing was aimed at this: 150 thousand of the total of almost 750 thousand.
But this number could be lower - much lower, thinks Hendriksen. Last week the RIVM held a symposium in Utrecht to advertise this to their colleagues and other interested scientists. New technologies make it possible to substitute live test subjects with in vitro methods (test tubes and analytic equipment). Synthetic vaccines, which can be tested for composition inside machines, could completely replace the current biological means and render one in five animal tests redundant.
Partly this is 'pure science fiction', warned researcher Dr. K. McCullough of the Swiss Institute of Virology and Immunoprophylaxis. On the other hand, the first vaccines tested according to this procedure are already on the market. One example is a vaccine for hepatitis B that is derived from yeast, and that can be analyzed with a gas chromatograph. 'In the area of animal testing there is still a lot to gain this way', says the Professor. 'Which is a good thing, because the total number of animal tests hasn't been going down but up for some years.'
The production of medicine or vaccines may seem a high-tech affair to outsiders, but the basic principles are often surprisingly primitive. Some vaccines are still grown in simple half-liter bottles and produced in relatively small quantities of a hundred to a thousand liters per batch. Because in principle every batch can be different, new laboratory animals have to be used to screen the quality of each production batch.
This is done with 'challenge testing', in which a group of usually twenty animals are administered four different doses of the vaccine. Then they are injected with the infectious organism, and their reactions are screened. This way they are proving time and time again the effectiveness of a substance, by dying or surviving after receiving a dose that is deemed to be lethal.
This is a reliable method, almost fifty years old and made mandatory in legal regulations. Only at the RIVM thousands of test animals die each year to guard the effectiveness and quality of vaccines for e.g. tetanus, whooping cough and diphtheria.
And this is a relatively low number, because many more animals are dying in test laboratories of the Dutch veterinary medicine industry. Mice are used the most, followed by rats, guinea pigs and rabbits, and a smaller number of dogs, chickens or pigs when vaccines are made especially for these animals.
An arithmetical analysis of old test reports made by RIVM researchers proved ten years ago that the reliability of tests is not compromised when the number of specimens in each control group is decreased from twenty to twelve. This number can even be brought back to eight, when all that's being done is taking blood from the animals and analyzing that, instead of waiting for the animals themselves to get ill.
'The problem is that the reliability of this method still has to be proved, says the Professor. The authorities that have to decide whether or not new methods are allowed are basically conservative. The RIVM has to deal with the European Pharmacopoeia, an institute of the European Council.
Pathetic mice do not count as a valid argument on this level, he knows. This was confirmed last week by many foreign researchers in Utrecht. It's nice that the number of test animals can be reduced, but more important is that these tests with analytic machinery and test tubes are more reliable, cheaper and easier to reproduce.
'This is also the reason why underdeveloped countries are interested in this technology. Many have their own vaccine production for which they use enormous animal testing laboratories. I visited institutes in Vietnam and Indonesia, that each held half a million test animals. The object is not so much to reduce the use of test animals, but to reduce cost, coupled with the fact that animal testing under tropical conditions is often difficult to do.'
In Holland the ethical aspect is more important, but Hendriksen is not completely satisfied. At his inauguration as extraordinary Professor Alternatives for Animal Testing at the Scientific Center of Animal and Society (WCDM) in Utrecht last year, he pleaded for a stricter justification of test animal use by scientists.
Half of the Dutch test animals are used at universities, for all kinds of promotional research. 'Everyone should be made to explain in their thesis why they have used test animals and why there was no alternative. Researchers still don't give possible alternatives sufficient thought.'

     
In 1978 one and a half million test animals were used in Holland. After a strong decline in the eighties this number stabilized at approximately seven hundred thousand. But in the last two years this number has been rising again, mainly because of an increase in the use of genetically engineered mice. He feels that action clubs and organizations that are against test animals should occupy themselves more emphatically with daily reality.
'They have to score with their followers and so they aim at the more cuddly animals, because they are supposed to be the most sad. But that's not where the biggest problem is, apart from the argument that these roughly six hundred monkeys usually don't die from testing and aren't involved in the really nasty experiments. Over 60 percent of all test animals are mice and rats, and sometimes it seems like nobody cares about them.'
     

By Jeroen Trommelen, translated by Lia Belt. This article appeared in the Dutch Volkskrant on 12th November 2001.
The Dutch article is copyrighted: copyright © 1999 Media Resultant b.v., resp. the original publisher and/or authors.