The History of in vitro Cytotoxicity Testing in Germany

When starting my own business in 1980 one of the first targets was to establish in vitro cytotoxicity testing of medical devices and materials intended to be used as part of medical devices. In my Munich environment I identified three institutes with expertise in mammalian cell culture, and established cooperation with each of them 

• The Virology Department of the Max von Pettenkofer Institute of the Ludwig Maximilian University (LMU)
• The Institute for Pharmacology and Toxicology of the Ludwig Maximilian University 
• The Working Group of Dr. Rupert Timpl at the Max Planck Institute (MPI) for Biochemistry

The first project, where I intended to include cytotoxicity testing as a screening method, was a development project for new contact lens polymers. My client was a German contact lens manufacturer who had applied for public funding by the Federal Ministry of Economics. In their response to this application the Ministry decided that in vitro cytotoxicity testing is not an established method, and therefore needs to be excluded from funding. The decision referred to consultation with the Federal Agency for Health (Bundesgesundheitsamt, BGA). Soon later I attended a seminar about mutagenicity and genotoxicity testing at the BGA. On this occasion I asked the organizer of the seminar, Professor Rolf Bass, if he had been involved in the consultation with the Ministry of Economics, and learnt that the colleague responsible for medical devices had asked him ‘on the floor’, what he knew about in vitro cytotoxicity testing, and Professor Bass had denied any personal experience.

In spring 1982 I decided to approach Professor Helmut Greim, Director of the Institute of Toxicology at Munich Technical University and of the Institute for Toxicology at the GSF Research Center for Environment and Health (now Helmholtz Institute). At that time Professor Greim was also the Chairman of the German Society for Pharmacology and Toxicology. Professor Greim listened to my targets and experiences, and finally agreed to cooperate in the validation of in vitro cytotoxicity testing versus established animal test methods. Professor Greim approached the Secretary of State at the Federal Ministry of Science, and received his supportive opinion and encouragement to apply for public funding. Together we developed a 300 pages proposal for funding, with detailed reasoning, literature, and working plans for 30 months. Greim submitted our proposal to the Ministry of Science. On 06 December 1982 we were invited to a hearing with the Scientific Advisory Committee headed by Professor Herbert G. Miltenburger. The Committee was not sure whether or not to support our proposal, which resulted in a non-funding decision by the Ministry.

1983 was in Germany a year of public demonstrations against the use of animals for testing purposes. In this situation the Ministry recalled our proposal, and in 1984 – based on our submission of 1982 – called for applications for public funding to establish in vitro cytotoxicity testing. Under this program 30+ laboratories received public funding. My laboratory did not apply because we had in the meantime already established routine test methods for cytotoxicity testing.

When in 1989 the German Institute for Standards (DIN) established the Committee for Biocompatibility Testing of Medical Devices, we decided to invite two experts from the ‘activist group against animal tests’ as permanent members of our committee. Thus we communicated how we ensured that our work contributed to minimizing the number of animal experiments and the extent of suffering of animals, while at the same time ensuring a high level of safety and performance of medical devices.