Worn down and financially exhausted, but more popular than ever
When academic toxicologists in a German state join forces, it is virtually headline news. This is because the discipline is on the red list. Only in Baden-Württemberg does the number of toxicologists at university institutes justify the joining of forces. The ironic thing about this is that the competence of the rare species ”toxicologicus” is in greater demand than ever.
Therefore, the gripes from toxicologists at the 3rd symposium of ToxNet BW in Ulm regarding the long-standing blood letting in research and education almost have something of the ritualistic about them. Such lamentations are nothing new and come from industry (VCI) and science (Science Council and DFG) alike.
The toxicologists at the symposium in Ulm claim that such lamentations are no longer heard, but they still complain that the discipline has experienced a "massive loss of institutes and chairs in Germany and Europe." Many universities only have pharmacological institutes, which incorporate the discipline of toxicology.
REACH exposes lack of toxicologists
The broader public is gradually becoming aware of the lack of toxicological institutes and chairs due to REACH (registration, evaluation and authorisation of chemical substances; REACH is a European Community Regulation on chemicals and their safe use). Safety tests have to be run on around 30,000 old chemicals. This is work that requires toxicologists. Back in 2006, the chemistry lobby warned that “academic toxicology in Germany is at serious risk of being unable to effectively carry out research and training as a result of the gradual emaciation of the resources available for research and education”. Since then, four industry-sponsored toxicology master’s courses have been established in Germany.
Bleed-out of toxicology - why?
Toxicological know-how is in great demand at universities, research institutions, in the industry (chemistry, pharma) and in government agencies. Nevertheless, the discipline is suffering from bleed-out. The search for causes throws up many answers: an outdated discipline, which was easily abolished as part of the cost-savings required following German unification; bad self-marketing; toxicology often comes under the umbrella of medicine, where it is not quite its real place; clinicians "do not often realise immediately what purpose toxicology serves" (toxicologist Michael Schwarz from Tübingen).
In the past, the discipline's closeness to application attracted the suspicion of basic scientists. The toxicologist Alexander Bürkle from Constance believes that the discipline still suffers from this "bad reputation". Other representatives of the discipline, including Holger Barth from Ulm, are of the opinion that traditional toxicology did not focus on progress in good time, focusing instead on describing things, which made it relatively unattractive for researchers.
A very broad field
Human toxicology has developed from medicine and pharmacology into an independent scientific, strongly interdisciplinary area. It includes general toxicology, food toxicology, regulatory toxicology (threshold values), occupational toxicology (the toxicology of occupational substances, monocyclic aromatic hydrocarbons), ecotoxicology, immunotoxicology, reproduction toxicology, clinical toxicology as well as test strategies in the toxicological testing of drugs and chemicals. These disciplines require researchers to have fundamental knowledge of biochemistry, biology, chemistry, genetics and physiology. A quick look at the courses offered for natural scientists undertaking further training to become expert toxicologists demonstrates this broad spectrum.
Exchange at symposia since 2006
Baden-Württemberg's university toxicology departments have the critical mass for networking. (It is worth noting that Baden-Württemberg's toxicology activities did not come out of various cost-saving programmes unscathed: in 2000, the Tübingen-based Institute of Toxicology became part of the Institute of Pharmacology (a toxicology professorship donated by the former Hoechst AG to the University of Mannheim was quickly redesignated). The loose cooperation of toxicologists, which was initiated by Albrecht Wendel from Constance who has now retired, has been organising symposia since 2006. The driving forces behind these networking activities are Michael Schwarz from Tübingen and his colleague from Constance, Alexander Bürkle.
This year, toxicologists and toxicology students from Karlsruhe, Tübingen, Freiburg, Constance and Ulm met in Ulm to report on and discuss new projects. Representatives of the regional pharmaceutical industry also gave presentations. ToxNet BW has the objective of improving toxicological education and research in Baden-Württemberg, promoting scientific exchange and turning joint research objectives into reality in the not too distant future.
Best career options
Toxicologists-to-be are now benefiting from the bleed-out of the discipline at German universities; there are hardly any jobs available and headhunters are used to find toxicologists; the career perspectives in industry, administration and research are optimal, said Michael Schwarz.
The toxicologist at the Tübingen-based Institute of Pharmacology and Toxicology is a member of the Toxicology Association within the German Association for Experimental and Clinical Pharmacology and Toxicology and in charge of the training of natural scientists who want to become toxicological specialists.
Heterogeneous research foci in Baden-Württemberg
The research foci in the field of toxicology in Baden-Württemberg are as heterogeneous as the subject itself. According to information from Manfred Metzler, toxicology at the KIT is part of the (University) Institute of Food Chemistry and Food Toxicology at the Natural Sciences Faculty (South Campus). The two professorships focus on food toxicology, particularly plant substances and contaminants such as mould toxins (a research priority funded by the Baden-Württemberg government since 2005).
The Institute of Toxicology and Genetics (ITG) at the KIT (North Campus), which was previously part of the Karlsruhe Research Centre, deals with the investigation of the molecular mechanisms of normal and pathological processes in the bodies of humans and animals. Two research groups are working on toxicological issues: the work group of the institute’s director, Uwe Strähle, who also holds a professorship at the University of Heidelberg, has plans to develop (transparent) zebra fish embryos into a molecular toxicological test system. Carsten Weiss’ research group deals with the toxicological effects of genotoxins (especially polycyclic aromatic hydrocarbons) and nanomaterials on the molecular level.
The University of Constance has numerous toxicology professors. Alexander Bürkle (Department of Molecular Toxicology) deals with the molecular mechanisms of DNA repair, which involves a particular focus on carcinogenesis. The university at Lake Constance also has a professorship in environmental toxicology (Prof. Dr. Daniel R. Dietrich). In addition, the Doerenkamp Zbinden chair for in vitro alternative methods to animal experiments (endowed chair, Marcel Leist) is also part of the University of Constance.
At the University of Ulm, Holger Barth works on bacterial toxins. His particular focus covers two aspects: the characterisation of molecular and cellular mechanisms of action and their pharmacological application. The Institute of Experimental and Clinical Pharmacology and Toxicology at the Freiburg University Medical Centre led by Klaus Aktories also deals with bacterial toxins, with key focus on toxins such as the Clostridium botulinum Cw3 toxin that has an effect on the cytoskeleton.
Michael Schwarz from the Tübingen-based Institute of Experimental and Clinical Pharmacology and Toxicology focuses on chemical cancerogenesis, investigating the risk of cancerogenic compounds. Schwarz is also involved in EU projects on the development of alternative test methods on which huge expectations have been placed since researchers (Hartung et al.) have produced estimates that the capacities required for the testing of chemical substances exceed the official figures on the number of animal experiments and hence cost a great deal more than envisaged.
Dilemma: no complex safety tests without animal experiments
The dilemma faced by regulatory authorities, industry and research is that huge effort is being put into the development of alternatives to animal experiments in Europe (see Progress Report) and elsewhere (in the USA through the NIH), but that complex toxicity tests assessing the effect of cancerogenic or teratogenic substances cannot be done without animal experiments. This was the result obtained in a study carried out on behalf of the German Toxicology Association in 2008 (Lilienblum, W. et al.).
Schwarz believes that there is a realistic chance of reducing the number of animal experiments (for example, tests whose effect can be directly measured on the skin), but nevertheless regards the possibility of avoiding animal experiments within the next ten years as illusory.
Michael Schwarz confirms the statement by the American researcher Hartung (originally from Germany): “The problem is that REACH will exceed the test capacities in Europe” in terms of reproduction toxicology. In this area, 2,000 to 3,000 chemicals are waiting to be tested for reproduction toxicology testing in two-generation studies where up to 3,200 rodents (usually rats) are required per study. These investigations are very costly and time-consuming considering the average lifespan of the animals, which is 18 months to three years. Schwarz believes that the fact that such studies need to be carried out for all 3,000 chemicals exceeds the worldwide capacity of toxicological institutes.
Toxicology offers exciting basic research
Although the development of alternative methods to animal testing might take much longer than anticipated, making the paradigm change in the field of toxicology in the 21st century far off, one thing nevertheless seems to be evident: toxicology is becoming more attractive for young scientists due to the fact that the USA and Europe are spending a lot of money on basic research. According to Carsten Weiss, the Americans are currently working on a revolutionary project, in which they are trying to establish human in vitro systems because in vivo models do not have any predictive value.
Lilienblum, W., Dekant, W. et al.: Alternative methods to safety studies in experimental animals: role in the risk assessment of chemicals under the new European Chemicals Legislation (REACH), Archives of Toxicology 2 (4), 211-236 (2008) 211-236 (2008), DOI 10.1007/s00204-008-0279-9.
EU-Kommissions-Fortschrittsbericht zu alternativen Testmethoden (download from: https://www.biooekonomie-bw.dewww.nks-lebenswissenschaften.de/aktuelles/Download/dat_/fil_846)
National Toxicology Programme of the USA: https://www.biooekonomie-bw.dentp.niehs.nih.gov/
Thomas Hartung /Costanza Rovida: Chemical regulators have overreached, in: Nature 460, 1080-1081 (27 August 2009) | doi:10.1038/4601080a
Gilbert, Natasha, Chemical-safety costs uncertain, in: Nature Vol. 460/27. August 2009, p. 1065
VCI (Ed.): Empfehlungen des VCI zur Toxikologieausbildung im Rahmen von Master-Studiengängen für Studierende der Chemie und verwandter Fächer, October 2006.
ZEBET - Centre for Documentation and Evaluation of Alternatives to Animal Experiments: https://www.biooekonomie-bw.dewww.bfr.bund.de/cd/1433