Practical difficulties in balancing harms and benefits in the modern use of laboratory animals: biotechnology.

Every ethical review process presupposes a set of ethical criteria, proper procedures and a consistent legal framework. The Netherlands became unique in 1996, by the decision of the Parliament to start a national ethical review procedure regarding the ethical aspects of genetic modification of animals (Animal and Biotechnology Decree). Due to the policy of public disclosure of all relevant documents and providing a legal trajectory for public objections, extensive ethical arguments pro and con are well documented. This paper lists and analyses the misconceptions when one tries to apply the "classical" ethical framework of harms and benefits to the new designs of animal experiments in the context of biotechnology. For instance, what is the object? The foster mothers, the manipulated egg cell, the malformed embryo, the pups dying before weaning or the adult mice in the experiments? The public considers the whole methodology ethically relevant. Most researchers tend to check out only "consciously" experienced harm, which implies only autonomously living mice and not a cell or an embryo. And, what is the domain of benefits? An exciting construct to be incorporated in the genome, the healthy birth of a surviving knock out, or a successful experiment with adult genetically modified mice? In the same way, the question for relevant alternatives in the "classic" sense of the Three Rs seems to shift completely to a discussion about goals in the far future. Is this modification absolutely necessary, or are the goals also reached by research strategies without genetic modification?