Science - December 4, 2008

PAIN-FREE LAB ANIMALS

The laboratory animal of the future will suffer no pain or discomfort, won’t need feeding and can take a few knocks. All he needs is a bit of electricity to keep him going. The new lab animal is a computer, and this is what PhD student Jochem Louisse has been working on for a year. Louisse describes himself as an animal biologist, but real animals hardly come into his research.

Lab animals in the Central Veterinary institute in Lelystad.
The laboratory animal that Louisse is working on at the Toxicology chair group is really just a model with mathematical formulae for predicting exactly what will happen in your body after a substance is ingested, where it will accumulate and what the concentration in the blood will be. This data is used to translate effects of toxic substances which have been measured in tissue cultures in vitro into human terms. Ideally, no animal experimentation is involved.

Louisse is in the vanguard of a new Wageningen discipline, formally launched last month with the appointment of TNO scientist Ruud Woutersen as Associate Professor of Translational Toxicology. This discipline is all about translating the effects of poisonous substances measured on lab animals into human terms. The traditional approach is to determine the effect of a toxic substance on a rat, for example, and extrapolate to the human being. Translational toxicology aims to develop new methods, and Louisse is working on one of them.
With Woutersen’s appointment, Wageningen is responding to a growing interest in alternatives to animal testing in toxicology, due in part, Woutersen believes, to the European Reach programme that obliges producers to publicize the dangers of chemical substances. ‘Industry works with about 300 thousand different chemicals, 30 thousand of which are produced in large quantities. But we still know very little about many of these substances. Reach stands for registration, evaluation and authorization of chemicals. We are now at the registration and evaluation stage.’
And this is generating mountains of information, but is also revealing how little is known about the dangers of many substances, says Woutersen. This is where toxicologists come in. ‘And really, we shouldn’t make use of animal experiments for this research.’ Besides the stricter European regulations, animal testing is time-consuming and expensive – and it is under fire for ethical reasons.

Louisse’s computer model could provide an alternative to animal testing: the lab animal in silico. But a model isn’t much use on its own: it stands or falls with the quality of in vitro testing. For this purpose, Louisse uses a clump of undifferentiated stem cells which serve as a model for an embryo. ‘With this approach, you can demonstrate at an early stage whether a new substance is toxic for the embryo. And this is something that animals would otherwise be used for’, says Louisse.

And once it’s all up and running, the question is how quickly the computer lab animal can get to work. Woutersen feels it takes too long for new knowledge to be integrated into rules and regulations. Government is very cautious. But this is not just the government’s fault, says Woutersen – it involves society as a whole. ‘We may all have to accept a bit more risk. If we can’t accept that, we’ll never get anywhere. And then you can’t ban the use of animal testing – unless you say, ‘Test it on me’. But I don’t think society is ready for that.’

LESS ANIMAL TESTING
Animal testing is in decline in the Netherlands, and that’s true of Wageningen too. The university used 11,963 animals for experiments last year: ten per cent less than the year before, and forty per cent less than in 2004. (The figure does not include the institutes.)
Wageningen University accounts for two per cent of the total number of animal experiments in the Netherlands. Testing on live animals has been most drastically cut back in education, where films, CD-ROMs and plastic models are being used instead. Nevertheless, in Wageningen last year, 969 animals – half of them fish – were sacrificed to educational ends.

Re:act