Helmut Greim, born May 9, 1935, in Berlin, studied medicine at the University of Freiburg and the Free University of Berlin. Based on his experimental work on the digestion of infants with diarrhea, he received his MD in 1962 and thereafter joined the research group of Prof. Herbert Remmer at the Institute of Pharmacology (director Prof. Hans Herken) of the Free University. When Remmer in 1965 became Director of the Institute of Toxicology, University of Tübingen, Greim followed him receiving the position of an assistant at the institute. There he continued his research on cytochrome P450, and in 1970, after determining the half-lives of at that time only known two P450 enzymes received his habilitation. Thereafter, he accepted the position of a visiting Research Associate Professor at the Dept. of Pathology, Mount Sinai School of Medicine of the City University of New York (Chair and Dean Dr. Hans Popper). During this time, he also held the position of Visiting Fellow of Pharmacology at the Yale School of Medicine in New Haven, Connecticut. Research at Mount Sinai focused on the P450-mediated metabolism of bile salts during cholestasis (Greim et al. 1972), of carcinogens and mutagens and the introduction of Phase I metabolic activity into the Ames test (Popper et al. 1973). These research activities continued in Tübingen after Greim’s return to the institute in 1973.
After Greim became director of the GSF toxicology in 1975, the group expanded rapidly and became an institute in 1978. In 1988, the institute moved into the new and spacy well-equipped building (The “Tox Building”) (Fig. 3).
Fig. 3The “Tox Building” of the GSF in Neuherberg (provided by Prof. Hans Zischka)
Research focused on developing and standardizing in vitro test methods including characterization of metabolizing enzymes of commonly in toxicology used cell lines, establishing rat hepatocytes and V79 cells with competent metabolizing capacity to investigate cytotoxicity, genotoxicity, and DNA repair of chemicals (Greim et al. 1975, 1980; Doehmer et al. 1994).
Studies on the mechanism of carcinogenesis and mutagenesis included intercellular communication, cell proliferation, and apoptosis, and to extrapolate results from animal studies to humans, physiological-based pharmacokinetic (PBPK) models have been developed and applied for many carcinogens (Peter et al. 1987). The toxicology of metals included molecular mechanisms of copper exposure of infants and biomonitoring of mercury after the removal of amalgam fillings.
Participation in the “reactive oxygen club” organized by Prof. E. Elstner, Institute of Biology und Microbiology of the TUM, improved the understanding of consequences of inflammation resulting in the reactive oxygen species during inflammation and cytotoxicity.
Together with the toxicologist Frederick Coulston, Albany Medical College, New York State, USA, the institute became responsible for the research activities at the former NASA facility in Alamogordo, New Mexico, which kept monkeys and apes for research purposes. From the German side, this has been supported by the Federal Ministry of Research and Development. There, several studies on the effects and elimination of dioxins in rhesus monkeys have been conducted (Rozman et al. 1981). After the end of these activities, several members of the GSF Institute of Toxicology stayed in the USA and received positions at the Institute of Toxicology, Kansas City University. One of them, Dr. Karl Rozman, became a member of the US TLV (threshold limit values) committee of the American Conference of Governmental Industrial Hygienists (ACGIH) and served as a liaison officer between the German MAK Commission and the TLV committee.
In 1987, after declining the positions of chair and director of toxicology at the Universities of Tübingen and Vienna, Austria, Greim became director of the newly founded Institute of Toxicology and Environmental Hygiene of the TUM (Fig. 4). This further expanded research and teaching activities in toxicology for medical students but also for students of chemistry at both Munich universities. With the assistance of the president of the TUM, Prof. Wolfgang Hermann, and the vice president of the University of Tübingen, Prof. Ernst Bayer, both chemists, lectures in toxicology for students in chemistry became mandatory for students of chemistry at German universities.
Fig. 4At the time when Greim retired in 2000, the institutes had a total of 120 coworkers including the scientific secretariate of the MAK-Committee (Commission for the Investigation of Health Hazards of Chemicals in the Work Area of the German Research Foundation), which Greim chaired. In 2003, his successor, Prof. Dr. Martin Göttlicher, became director of both the TUM Institute of Toxicology and Environmental Hygiene (Fig. 5) and the GSF Institute of Toxicology, now the Helmholtz-Institute of Molecular Toxicology and Pharmacology, specifically investigating the molecular mechanisms of bioactive chemicals with the specific aim to develop effective and safe drugs (Einer et al. 2023).
Fig. 5Institute of Toxicology and Environmental Hygiene of the TUM (provided by Prof. Hans Zischka)
In the institutes of Food Chemistry and Analytical Food Chemistry of the TUM School of Life Sciences in Weihenstephan, phytotoxins are identified and evaluated regarding their relevance for food safety.
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