From Research Magazine
Bart De Wever has worked in the field of human
skin culture for many years. Not for transplantation,
but as a means of testing the effects of cosmetic
products. De Wever explains: 'There is
a real need for alternatives. First and foremost,
there is, of course, the suffering inflicted
on so many laboratory rabbits. However, we are
also facing another problem. The skin and cornea
of the rabbit differ considerably from those
of humans and therefore do not always accurately
predict the way in which a human will respond.
Clearly, it is high time to use an alternative.'
De Wever has developed a method for culturing
skin, corneal tissue and oral mucous membrane
tissue. 'Tissue
cultured "in vitro” (in an artificial
environment) is a very good alternative. It is
an excellent way of testing the toxicity and effectiveness
of products.' How does De Wever go about
this process? 'We take cells from human tissue - from
skin that is removed during a surgical procedure,
for example. We isolate the individual cells from
the tissue and then put them into small plastic
beakers that have a permeable membrane in their
base. The cells are fed by this membrane and start
to grow. After about two weeks, tissue - in
this case, skin - has formed. We then expose
the cultures to the air. Under these natural
conditions the cells mature, and well-keratinized
skin or a strong cornea forms.'
Does this mean that, within
a few years, laboratory rabbits will no longer
be needed? De Wever: 'We
are still at the pre-validation stage, in which
we have shown that the results from our models
are comparable to those from the animal model.' To
facilitate this process, De Wever chose twenty
substances that had already been tested on rabbits.
Based on the results of these rabbit tests, ten
of these substances had been classified as non-irritants,
and ten others as either mild or strong irritants. 'We
applied these substances to the cultured corneal
tissues and studied the reaction. The traditional
Draize Test measures the degree of redness of the
rabbit's eye and observes how long it takes
for the redness to disappear. The substances
that cause redness in normal skin or corneal
tissue are called cytokines. The cultured tissue
also produces cytokines, and we are able to measure
these. Cells will die. If the rate of cell death
is low, this means that a substance is not a
strong irritant. And if cell death is high, the
opposite is true.'
However, De Wever was not completely satisfied.
He went on to test his results by using the same
number of substances in comparable tests on cows' eyes
(obtained from a slaughterhouse) and snails. 'Our
findings were confirmed once again by the results.
We demonstrated that ten of the chosen substances
were irritants. But our tests showed that three
of the ten substances that were not actually classified
as such, were, in fact, irritants.' This
was confirmed by hospital data obtained from people
who had experienced problems after getting one
of these three substances in their eyes. Our findings
were confirmed from all sides. 'It's
cause for concern that the information on toxicity
contained in data banks is based on rabbit tests
and indicates that these three substances are completely
harmless. In actual fact, it has been shown that
they do cause irritation.' For further confirmation
of his results, De Wever carried out his experiments
in the laboratories of no less than four large
pharmaceutical companies. The results were repeated
in every laboratory, which proves that De Wever's
in vitro test is reproducible. The same cannot
be said of the Draize Test. 'At one time,
three substances were tested on rabbits in 24
different laboratories. Every laboratory came
up with different results. Clearly, they were
not reproducible.'
Professor Frans Ramaekers - a professor in
Molecular Cell Biology and De Wever's supervisor - organized
a small symposium on the occasion of De Wever's
Ph.D. thesis defence. 'At this symposium,
internationally renowned scientists exchanged views
on alternatives to animal experimentation. Representatives
of the pharmaceutical industry showed a great deal
of interest as well. De Wever's research
is also of great importance to this group. From
2009, cosmetic products that have been tested
on animals may no longer be sold within the European
Union. As a result, the hunt for alternatives is
in full swing. Both from an economic and from a
political point of view, Bart De Wever's
research is attracting a great deal of interest.'
Throughout Europe, De Wever's alternative
is seen as important for the near future. Bart
De Wever says: 'The European Commission is
shortly planning to test the toxicity of 30,000
commonly used chemical substances because there
is not enough toxicological data on them. There
is a real need for a data bank. It is estimated
that this research will
entail four million animal experiments and will
cost €2.5 billion. Putting
aside the question of capacity, I should point
out that, even if all the laboratories in Europe
were to work on this full time, the research wouldn't
be finished until 2057. The decision has now
been made to test the most commonly used substances
first.'
Bart De Wever is critical of the so-called toxicology
bibles. 'Government employees take these "bibles” too
literally and accept them unquestioningly. Even
worse, people who question them are considered
to be nuisances. But the fact of the matter is
that you cannot always satisfactorily compare animal
experiments with the human situation.' Unfortunately,
it could be another ten years before the alternatives
are validated. 'But at least we are on the
right road,' says Bart De Wever. 'Three
of the largest pharmaceutical companies in the
world have supported my doctoral research. The
cosmetic industry is almost certainly going to
adopt this animal-friendly and cheap method.'
Dr Bart De Wever is Business Development Director
of Phenion,
a 100 % affiliated Henkel company, the competence
center for the development and validation of alternative
methods to animal tests. Tel: +32.494.507.886.
E-mail: B.dewever@phenion.uni-frankfurt.de
Professor Frans Ramaekers is a professor
in Molecular Cell Biology at the UM Department
of Genetics and Cell Biology. He is also attached
to the Growth and Development Institute (GROW),
where De Wever carried out his doctoral research.
Tel: +31 43 388 13. E-mail: f.ramaekers@MOLCELB.unimaas.nl |