Bioassays are performed to ensure a constant quality of medicines derived from biological sources. These tests are stipulated for some drugs in the German and European Pharmacopoeias. They are justified because physico-chemical or other analytical methods may not be appropriate to define exactly the potency of the drug in each individual batch and/or to detect any biologically relevant impurities. However, the implementation of good manufacturing practice and the technological progress in manufacturing and in analytical methods in the last few years raise the question whether some traditional bioassays can be replaced by new alternative methods which do not require biological tissues or animals. With respect to this topic the pharmacopoeias were reviewed and some proposals are presented in this paper. However, these approaches can only be realised when all parties involved - pharmaceutical industry, regulatory authorities and others - co-operate in the challenge to replace - wherever possible - bioassays by appropriate alternative methods.

Oxidative damage in the vascular system has been linked to the development of atherosclerosis. The aim of the present study was to establish a cell culture model for the investigation of in vitro induced oxidative DNA injury, its modulation and repair kinetics. Primary cultures of human coronary artery smooth muscle cells were used as target cells. The cells were exposed to hydrogen peroxide (H2O2). DNA damage was quantified by the alkaline single-cell gel electrophoresis assay (comet assay). This method allows quantification of DNA single and double strand breaks and of alkali-labile sites in individual cells. In the present study H2O2 concentration-responses and dependence of damage on exposure time and temperature were evaluated and the repair kinetics were studied. The results show that this cell culture model can be employed to study oxidative DNA injury in the cells of the human cardiovascular system, a promoter of cardiovascular disease. Further it offers the possibility to investigate pharmacological modulators of such oxidative effects. Such modulators are antioxidants like vitamin C and E, steroid hormones, phytoestrogens, or synthetic agents. Today, pigs, rabbits or rats are used to test systemic and local administration of the named modulating substances, the latter by use of special catheters or stents placed inside the arteries. These experiments require treatment observation over a number of weeks and killing of the animals at the end of the experiment. By using the proposed cell culture model such animal experiments could be partly avoided.

The history of biomedical research clearly shows that, with exception of a very few, scientific findings could be realised only with the help of animal experiments. Unfortunately, in the past the life of animals was treated negligently and, at times, in fact criminally. Only the researchers' willingness to apply ethical principles toward laboratory animals could create a climate in which research is opening up to constructive, active animal protection and is ready to co-operate through the implementations of such programmes as the 3R-principle into daily practice. Using a number of examples, the article at hand tries to show that the dimensions concerning animal protection is very old indeed and that only a change of consciousness by the public and in research has created a situation in which a gentler treatment of life and life conditions of laboratory animals could be realised. A further development of "constructive" animal protection within the industrialised nations is only possible with this back ground. Without such a development, biomedical research is bound for deficits in one way or another. It will be loosing it's medical and economical opportunities and with it, it's meaning for man.

My paper will focus on those events happening within the United States during the last year.
The issue of including or excluding rats, birds and mice from inclusion under the Animal Welfare Act has been a difficult battle for both those that wish to exclude them and those that wish to include these animals under this legislation. As of the writing of this abstract, the Senate, which originally intended to include rats, birds and mice under the Animal Welfare Act, has passed an amendment which will permanently exclude their listing under this Act.
During the last several years it has become clear that refinement, as one of the 3Rs, has and will become the most important set of activities to add humanness to animal experimentation. It is clear that refinement approaches provide the opportunity to possibly eliminate or significantly minimize any pain or distress in animal protocol. My presentation will focus on CAAT's (http://caat.jhsph.edu) activities in this important area.
Understanding potential health hazards to environmental industrial chemicals has become a major focus of activity both in the US, Europe and Japan. These programs offer the first opportunity to provide information, in the public domain, on these chemicals. One of the consequences, however, is the potential requirement for large numbers of animals. In the presentation, I will focus on two approaches to significantly including the 3Rs in these important programs.
Although it is common practice in Japan to recognize contributions of laboratory animals through a day of memorialization, this has not been the case in the United States. During the last year, several activities have been initiated to begin to institutionalize memorial services for animals used in research.
As the host institution of Altweb (http://altweb.jhsph.edu), the alternative web site internationally, current statistics and accomplishments will be provided on its worldwide utilization.

The use of animals for research and testing purposes has decreased substantially during the last two decades but is now increasing again, mainly because of the increased use of transgenic animal models. Presently, 10-12 millions of vertebrate animals are used per year within EU Member States. Scientists who are using animals in research are frequently criticised by animal protection groups and blamed that they do not respect the integrity of an animal's life. The European Science Foundation (ESF) is recognising that legislation cannot be the only answer to those worries in society and that it is essential to take a stand and to clearly explain what the Foundation's position with regard to the use of animals is. In a recently published position paper, ESF has discussed its views and has adopted guidelines for the use of animals in research. The document explicitly states that laboratory animals have an intrinsic value, which must be respected. The consequences of recognising the intrinsic value have been elaborated in the position paper and include, among others, strong endorsement of the replacement, reduction, refinement principles. It is stated that, prior to the performance of an animal experiment, the protocol should be subjected to independent expert review including the weighing of the likely benefit versus the likely animal suffering. Also, the development and organisation of accredited courses on laboratory animal science, including information on animal alternatives, welfare and ethics are encouraged. The guidelines, as formulated in the position paper, can be seen as reinforcement of developments that have already been started in several countries, but have not always received full support from the scientific community. With this document, the association of 70 leading national science organisations in Europe has taken a position that, in several aspects, exceeds current European legislative regulations. For bridging the science - society controversy, it is essential to continue this initiative by promoting the implementation of the guidelines at all levels of the scientific community. This requires commitment and scientific leadership.

ECVAM CORNER

NEWS
USA: Charles River bringt In Vitro Pyrogentest (IPT) auf den Markt
USA: Forscher unter strengerer Tierschutz-Aufsicht
EU/USA: InterNICHE vergibt Humane Education Award 2002
CH: Tierversuchsstatistik 2001 - keine Versuchstiere für Kosmetika
D: Fischei-Test in der Abwasserabgabenverordnung verankert
D: Nationaler Workshop: Der Hund als zweite Spezies für die Sicherheitsprüfung bei der Zulassung von Pflanzenschutzmitteln
D/CH: Neu erschienen: Die Würde des Tieres
D: Konzepte zum Tierschutzunterricht an Schulen
D: ALTEX-Preis 2001 geht nach Saarbrücken
F: Reconstituted Human Epidermis and Corneal Epithelium as Alternative Methods to Animal Testing
Sondermeldung aus aktuellem Anlass:
EU: Europäisches Arzneibuch verlangt seit dem 1.7.2002 weniger Tierversuche für die Prüfung von Impfstoffen
D: Paul-Ehrlich-Institut verzichtet auf Gebühren bei der Einführung von Alternativmethoden

COMMENT
Susi Goll: Tierschutz im Krebsgang. Zur schweizerischen Tierversuchsstatistik 2001

CALENDAR

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