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
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
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
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.'