No test-tube experiment, however sophisticated, can simulate Alzheimer’s – and even the best computer simulations must be tested on organisms to ensure the results are correct. To find answers to many scientific questions in health research, there is often no alternative to animal experiments.
Researchers at the MDC seek to elucidate the molecular mechanisms of health and disease. Thus we aim to understand the basic mechanisms of life. This knowledge will hopefully enable us to cure previously untreatable diseases, to develop new drugs and to reduce patient suffering. Or, to put it more abstractly: In the future, diseases should be treated in a more targeted way, be diagnosed earlier or be prevented altogether.
But the human body is a complex system. If we want to understand the processes involved in a disease or the detailed mechanisms of therapeutic agents, we often have to examine the entire living body – with its many tissues and organs, its blood pressure and hormones. Because in order to understand and treat diseases, we must take the interactions between different cell types, different organs and organ systems into account.
The necessary methods differ depending on the research question. Not every research project at the MDC works with laboratory animals. Are computer models, cell cultures, organoids or animal experiments what we need? And which organisms are best suited?
The most important questions and answers
Scientists at the Max Delbrück Center (MDC) are working to decipher the molecular mechanisms underlying human health and disease, and to translate their findings into clinical practice as quickly as possible. They analyze and try to understand the molecular and cellular basis of our cardiovascular system, metabolism and nervous system, as well as the molecular processes of carcinogenesis (cancer formation). The goal is always to discover and develop new medical diagnostics and therapies.
Put simply, the process starts with a hypothesis – for example, that certain genes or proteins are responsible for the development of a pathological biological process. This hypothesis is then verified using a model. Common models used to answer such questions include cell and tissue cultures. But when complex relationships between different tissues are being investigated, scientists require an intact organism as their model system. Typically, this is when a mouse model is used.
Mice present many advantages. They are mammals with a similar genetic makeup to humans (97.5 percent of their DNA is identical to that of humans). It is therefore possible to reproduce in mice the exact genetic changes that lead to the emergence of a disease in human patients. It also means that basic cellular processes – such as those that occur in the brain during a stroke or in the development of cancer – are comparable between mice and humans and make the mouse the most predictive animal model for many studies into human disease.
Animal research is one of the key pillars of and applied biomedical research. Milestones in medical progress such as vaccinations against polio, antibiotics to fight bacterial infections, the treatment of diabetes with insulin, or surgical techniques for organ transplants are all .
Our current knowledge of human disease as well as the many therapies that have been developed are largely based on the results of studies using animal models. The cellular processes that occur, for example, in the brain during a stroke or in the development of cancer are comparable between mice and humans. As a result, many diseases are able to be treated far more effectively today than they were 30 years ago. This is true, for example, of breast cancer, leukemia, and even HIV/AIDS. However, we are still waiting for breakthroughs in other types of cancer and in neurodegenerative diseases such as Alzheimer’s.
For about one and a half decades, a scientific debate has therefore been going on as to whether the mouse – the most widely used animal model in biomedical research – is still the most suitable model for developing new diagnostic methods and therapies. These doubts stem from the fact that a large proportion of the substances that have been identified over the past decades – for example, for cancer therapy – and tested on a mouse model were shown to be effective in mice, but not in clinical tests on patients. The reason for the low predictive power of such animal studies is said to be poor study design and the resulting overestimation of the study findings. Another criticism is that, although a laboratory mouse is genetically similar to humans, it is not a lifelike model.
Scientists at the MDC are working in various ways to make animal studies more predictive, which includes the careful conception, planning and evaluation of studies, as well as the development of so-called humanized mouse models. This involves, for example, genetically modifying mice to simulate the immune system of humans, or transferring to mice solely the genetic variants that are suspected to increase the risk of Alzheimer’s in humans. To make the mouse model more realistic, genetic patterns that appear to only increase the risk of Alzheimer’s in women are also only studied in female mice.
Since early 2015, a new building has been under construction on the Berlin-Buch campus – the MDC’s Preclinical Research Center (PRC). This new animal research laboratory will spatially restructure the keeping and breeding of laboratory animals at the MDC. Once the commissioning process is completed and all refurbishment work is finished, all the MDC’s animal research activities will move into the PRC. This means the new research building will only house mice, rats and other laboratory animals being used in studies, resulting in fewer transfers between houses for the animals, additional stress is avoided.
The new building will house laboratories designed to be used for experiments such as behavioral studies, but above all for state-of-the-art imaging processes such as micro CT, MRT or PET scans. These minimally invasive procedures allow scientists to conduct animal experiments in line with the 3Rs – inflicting less pain and suffering (refine) and using fewer animals (reduce).
The total number of mice and rats kept at the MDC will not increase with the new building. At best, the PRC will reduce it, as the spatial and conceptual coordination of all animal experiments in one building prevents overlaps and promotes a better exchange of experiences and results.
More information on research at MDC