Development of alternatives to animal testing – with 4.5 million euros of funds from Lower Saxony

News /

Fraunhofer ITEM is cooperating in the research consortium “R2N” (replace and reduce in Lower Saxony – alternative and complementary methods for forward-thinking biomedical research), funded with 4.5 million euros by the Lower Saxony Ministry of Science and Culture over a period of four years. In several subprojects, alternative methods of both basic and translational research shall be developed – with a special focus on ethical issues.

© Fraunhofer ITEM
© Fraunhofer ITEM

Reducing or even completely avoiding animal experiments has been part of Fraunhofer ITEM’s strategic orientation since the institute was founded 35 years ago. A broad range of in-vitro test methods – cell cultures as well as tissue cultures – has since been developed and further refined by Fraunhofer ITEM scientists, in particular with regard to the respiratory tract. The question of transferability of toxicological results from in-vitro experiments to the complex human organism is certainly one of the reasons why the regulatory authorities are rather reluctant to accept alternative methods. To improve acceptance of such methods, a gap in knowledge between insights gained from using alternative methods and their transferability to human health needs to be closed. This situation has been recognized and is now being discussed at different – including international – levels. An example is the comprehensive EU project “EU-ToxRisk”. Its aim is to lay new foundations for a paradigm shift in toxicology – towards more efficient and animal-free hazard and risk assessment of chemicals. An international consortium of 39 partner organizations from academia, industry and regulatory authorities is participating in this project receiving funding of 30 million euros. Fraunhofer ITEM is bringing in its expertise with a focus on inhalation toxicology.

In the research consortium “R2N”, Fraunhofer ITEM is involved in three subprojects. The subproject headed by Dr. Tanja Hansen is aimed at elaborating basic scientific principles that shall enable non-animal safety assessment of inhalable substances based on alternative methods in the future. By analyzing data of selected model substances known to have adverse effects on the lung, the scientists will try to identify a potential toxic mode of action and a dose-effect relationship for this effect. Individual effects contributing to the overall adverse effect profile will then be investigated in different in-vitro test systems. The lung cells will be cultured at the air/liquid interface and thus under conditions corresponding to the natural situation in the lung. The effects determined in vitro and their dose dependence will subsequently be used to derive a mathematical correlation intended to eventually enable extrapolation of the dose-effect relationship from cellular to organism level.

A pivotal contribution to this research project could come from precision-cut lung slices (PCLS), which are being explored by Dr. Katherina Sewald and her team at Fraunhofer ITEM. In viable lung slices, all cells are in their natural environment, so that responses of the lung to different chemicals or pharmaceuticals, but also to bacteria and viruses can be investigated here much better than in single-cell cultures, without the need for in-vivo animal experiments – a great benefit. Dr. Sewald is contributing her expertise to two subprojects performed in cooperation with the University of Veterinary Medicine Hannover. The first aim here is to set up a tissue and cell bank. The scientists then want to find out whether cell cultures generated from samples from the tissue and cell bank can provide a suitable basis to study in detail the features of new human and animal respiratory diseases caused by viruses. If so, they might also allow in-vitro investigation of diseases such as asthma or testing of the effects of drugs and immunomodulators in cell cultures – an aspect Dr. Sewald is already exploring in ongoing studies. An example is the project “InhalAb”, funded by the German Federal Ministry of Education and Research, which is aimed at establishing a test battery of in-vitro and ex-vivo models of the lung for preclinical testing of inhalable antibiotics as alternatives to animal testing.

“Our aim is to reduce animal testing in research and to confine animal experiments in the future to the inevitable minimum. By means of this consortium, we are promoting alternative and complementary methods. At the same time, we are attaching more importance to the social responsibility of science and to ethical issues,” said Gabriele Heinen-Kljajić, Lower Saxony Minister of Science and Culture. Key players within this consortium are Hannover-based institutions including the Hannover Medical School, the University of Veterinary Medicine Hannover, Fraunhofer ITEM, and TWINCORE, and in Göttingen the German Primate Center and Göttingen University Hospital.