Toxicological sciences in Switzerland Definition and scope

Toxicology is a multidisciplinary area of science that investigates the harmful effects of exogenous and endogenous factors on biological systems, with the objective to protect organisms, animals, man and the environment. Toxicological investigations provide a scientific basis for the understanding and the assessment of toxic effects. In this way, they provide relevant information for governmental agencies to establish safety and exposure limits. Apart from securing public health and the environment, toxicology becomes increasingly important for the evaluation and selection of technologies. It is an essential area for the assessment of benefits and risks of new products emanating from biotechnology and bioengineering on a rational and scientific basis. The awareness, the hopes as well as the fears of the public depend to a large extent on the expertise of toxicologists.

Switzerland is a world leader in the research and development of new drugs and in the production of pharmaceuticals. It also plays an important role in the area of fine chemicals. Of equal importance to the swiss economy is food processing. To maintain the lead in these areas, Swiss industries need highly qualified individuals in the chemical and biological sciences covering fundamental and applied aspects, including toxicology Toxicologists up to the doctorate level are essential for safety evaluation and risk assessment. For this reason, the academic institutions must provide a curriculum towards the formation of toxicologists.

Initiation of this report

The Swiss Institute of Toxicology in Schwerzenbach, an academic institution jointly operated by the University of Zurich and the ETH has been the center of toxicology for the last twenty years. It has conducted applied toxicological research and has provided expertise and post-graduate education. However the activities of this Institute have recently been found to be insufficiently adapted to the rapid growth in knowledge in biological and medical research and in technology, and it will cease its activities in the year 2001.

In light of this situation, the Swiss Society of Pharmacology and Toxicology has undertaken a review of the actual state of toxicology in Switzerland. The Swiss Academy of Sciences and the Swiss Academy of Medicine have supported this study financially and the Swiss Science Council has been consulted on several occasions.
 
In early 1998 a questionnaire was sent to 100 selected individuals actively involved in toxicology and the 48 returned questionnaires were used as a basis for the analysis given in this report. In addition, group hearings and meetings with scientists were held in Basel, Geneva, Lausanne and Zurich. Concurrently, the register of toxicologists in Switzerland, a Swiss continuing eduction program (Nachdiplom) for professional toxicologists, a website of the section of toxicology of SSPT, and the local Zurich "Center for Xenobiotic and Environmental Risk Research" were created.

Results

The study reveals that over 900 persons are engaged in the various fields of toxicology in Switzerland, 1/3 of them having an academic education and 2/3 a technical one. The main employers of toxicologists are in decreasing order : industry, universities or Federal Institutes of Technologies (ETHZ/EPFL), and governmental agencies. The current activities of toxicologists cover a wide range of areas ranging from the basic sciences to occupational safety, forensic toxicology and preventive medicine. With respect to academic research and education, Zurich is the main center followed by Lausanne, Geneva, Basle, and Berne. Industrial and food toxicology is concentrated within the multinational companies in Basle and the Lausanne area, respectively. Public advice in acute and chronic cases of poisoning and clinical toxicology services are provided by the Swiss Toxicological Information Center (STIC) in Zurich (Schweizerisches Toxikologisches Informationszentrum Zurich, STIZ). This center works closely with the clinical departments of the University Hospital in Zurich.

Identified issues and weaknesses of this study are as follows:

the lack of coordination and communication within and among the different centres became apparent from the majority of the questionnaires as well as from the hearings. These centers, involved in toxicology oriented research, were from academic, industrial, governmental and public sectors. The situation will worsen with the closure of the Swiss Toxicology Institute in Schwerzenbach in 2001
the lack of information flow from toxicologists to the general public was noted
the urgent need for more research, education and training in all fields of toxicology was emphasized by toxicologists from industry, government, and academic institutions
the potential lack of toxicological services and support in the near future was expressed by specialists from governmental agencies
Recommendations
Based on this analysis, the following proposals are put forward to improve basic and applied toxicological research and education in Switzerland:
 
RESEARCH

increased activity and support in the areas concerning biological and medical effects caused by xenobiotics (basic toxicology and ecotoxicology)
increased activity and support for safety investigations regarding new technologies on human health and the environment
coordination of multidisciplinary toxicological research activities throughout Switzerland
strengthening collaborations between basic research and applied/issue-related investigations
obtain additional resources for existing laboratories through the provision of toxicological services
benchmarking with toxicological research activities in other countries

EDUCATION

coordination among the locally existing education centres to provide interdisciplinary graduate and postgraduate courses, seminar series and continuing education in all aspects of toxicology
collaboration with on-going toxicological education programs in Europe, US and Japan
To translate the above proposals into action, we propose the creation of a Swiss network (SWISSTOX) with the following objectives and mission.

Collaboration: To establish close interactions and collaborative projects among the universities, the Swiss Federal Institutes of Technology, the industry and the governmental agencies in all aspects of modern toxicological research.
Education: To provide adequate integrated training programs for toxicologists and to implement a Ph.D. curriculum in toxicology.
Service function: To perform specific applied/issue-related toxicological investigations and to provide timely toxicological data for governmental agencies and industry.
Public relations: To communicate new developments and toxicological concerns to the public and to provide them with a brochure on Toxicology.
International relations: To expand links with toxicological centers and international societies in other countries.
In order to implement these recommendations, a follow-up study group should be formed. They will elaborate on a concise proposal regarding the structure, financing, timeframe, and the mission of the proposed SWISSTOX network.

Foreword and Acknowledgements

Hardly a week goes by without news of a chemical that could potentially threaten our health: pesticides or dioxin in food, pollutants in the air, chemicals in the water, toxic dump sites near our homes. Are these chemicals really dangerous? How much does it take to cause harm? What are the long term effects of chemicals with regard to risks for cancer, the nervous system or birth defects?

Finding answers to these questions is what toxicologists do. Modern toxicology has become multidisciplinary and is based in a variety of fields in science and medicine. It deals with the effects of chemical and biological substances on human and environmental health, defines potentially harmful interactions between endogenous and exogenous risk factors and investigates toxicological effects in experimental systems. In many cases toxicology is also involved in the definition of regulatory standards and legislation designed to protect human and animal health as well as the environment from deleterious damage by potentially harmful agents.
 
 

In the biomedical area, pharmacologists and toxicologists investigate the mechanism of action and effects of drugs. Toxicologists are concerned with the assessment of the toxic risk of xenobiotic substances for human and animal health. Clinical toxicologists are concerned with the pathogenesis, prevention, and treatment of acute and chronic poisonings. They are also involved in the clinical testing of specific antidotes and the elaboration of guidelines for the early detection and therapy of xenobiotic injury in humans and animals.

Important new developments and specialized disciplines of toxicology include "Molecular Toxicology" (e.g. toxicogenetics) and "Environmental Risk Assessment". These areas span a wide range of methodology ranging from molecular biology (e.g. molecular "biomarkers") to molecular and clinical epidemiology. In order to master these multidisciplinary tasks, future toxicologists working in different areas must closely collaborate and develop synergies and complementary functions in the elucidation of the mechanistic basis of toxic effects, in the prevention of chemical and environmental risks for public health and in the development of adequate intervention strategies in case of major chemical accidents.

With the rapid global development and use of new technologies, toxicology, in particular the domain of safety evaluation and risk assessment, will obtain an ever increasing importance. It represents an important tool in the evaluation and selection of new technologies leading to sustained economic development, safety of public health and protection of the environment. In industry, toxicologists significantly contribute to the safety of the products developed at companies such as at Novartis, Roche, Nestlé, Clariant, Ciba-Specialty, and Ares-Serono. Most of them were placed among the top companies in the Business Week Global 1000 list (see e.g. Business Week, pp. 49, July 13, 1998).

The Swiss Institute of Toxicology in Schwerzenbach, an academic institution jointly operated by the University of Zurich and the ETH, has so far fulfilled the role of a centre of education, research, risk assessment, information and public service. As toxicology is rapidly becoming a multidisciplinary discipline with exponential progress of knowledge in different subspecialities, revision of the traditional "one-centre" concept of toxicology in Switzerland is necessary. This concept has already been implemented on a local basis by the creation of a multidisciplinary "Centre for Xenobiotic and Environmetal Risk Research Zurich". This network serves as the nucleus for toxicological education, research and services among 18 local institutes in the area of Zurich.

On a national basis the Swiss Society of Pharmacology and Toxicology (SSPT) in collaboration with the Swiss Academy of Sciences and the Swiss Academy of Medicine has initiated an analysis of the current status of toxicology in Switzerland. A questionnaire was sent to more than 100 individuals actively involved in toxicology in order to evaluate their activities during the past 5 five years, their present situation and their prospects and needs for the next 5 years. In addition, several hearings and meetings were held in Basel, Lausanne, Geneva, and Zurich. The results were analysed and compiled by the office of HOVAT in Basel. A working group with delegates from universities, the Swiss Academies of Science and Medicine and the industry were involved in the coordination of the survey and in the evaluation of the results. From the very beginning support was provided by the Swiss Science Council (Schweizerischer Wissenschaftsrat/Conseil Suisse de Science), which is greatly appreciated, particularly the thoughts and comments of its president, Professor Verena Meyer.

We are very grateful to the coordinator, Dr. Christian Hodel (HOVAT), and his collaborators, Dr. Timo Buetler, Mr. Markus Grieder, and Mr. Thomas Zürcher, as well as Drs. Phaik Morgenthaler from the Institute of Pharmacology and Toxicology in Lausanne for their dedicated and continuous help.
 
Prof. Urs Rüegg 
University of Lausanne, 1015 Lausanne

President of the Swiss Society of Pharmacology and Toxicology (SSPT)
Dr. Beat Schmid
Novartis Consumer Health, 1260 Nyon
President of the Section of Toxicology of
the SSPT

Prof. Peter Meier-Abt
University of Zurich, 8091 Zurich
President of the Section of
Clinical Pharmacology of the SSPT

Conclusions

The present study has evaluated for the first time the state of toxicological science and its associated institutions in Switzerland. Although the topic is complex and the time frame of the study was limited, the information obtained from the questionnaire in combination with four hearings enabled a representative evaluation of the situation of toxicology in Switzerland.

Modern toxicology is multidisciplinary and its standard is highly dependent on the quality of basic and applied research in molecular biosciences, technology, experimental and social medicine and epidemiology. In many of these areas high quality research and service groups are available in Switzerland. In spite of this, several important issues were identified and need to be addressed.

After the year 2001 there will be no science-based institution devoted entirely to toxicology in Switzerland. As research and education are intimately linked, the Swiss academic institutions should take action to fill this gap. The somewhat scattered and isolated highly qualified research groups in toxicology present at various institutions could form the basis for a new structure of toxicology in Switzerland. However, a minimum of one professorship in toxicology with expansion of existing professorships dedicated to specific aspects of toxicology, as part of their main curriculum, are required to maintain educational and research needs. The academic institutions could provide the necessary basic research to increase knowledge and develop methods for future needs, such as mechanistic approaches for the assessment of new technologies and their inherent risk for human and environmental health.

Many institutions, including governmental agencies, have indicated insufficient in-house capacity and signalled a need for adequately trained staff. Services provided by experts in different research institutes and a continuing education programme could help to tackle this issue.

Future developments should be co-ordinated with industry who signalled a need for experts in toxicology. Industrial toxicology requires an academic partner and governmental agencies need experts who are familiar with international organisations, guidelines and requirements, as well as with our geographical, political, and cultural particularities.

There is a growing demand for toxicological expertise and risk assessment. Only well-trained toxicologists with extensive practical and theoretical experience are qualified to provide relevant answers and effective services.

There is growing public concern about health issues and rapidly expanding new technologies. The obstacles for the public and politicians are that there is no contact and information centre available where they can specify their requests for help and guidance. Hence structures with competent experts will be increasingly needed as providers of timely and relevant information and expertise. A major task of the responsible individuals will include the co-ordination and transfer of information between public, government, universities and industries.
 
Recommendations

The current analysis shows that there is significant competence in toxicology and related areas in Switzerland. However there is an immediate need for action due to the closure of the Institute of Toxicology in Schwerzenbach in 2001. New structures led by academic institutions ought to be created.

We recommend the creation of a network of the centers and/or laboratories with major interests in toxicology with a central reference institute, the Swiss Center of Toxicology (called SWISSTOX).
 
The Center for Research on Xenobiotic and Environmental Risk at Zurich is a local network using existing local competence within the two Zurich-based academic institutions. Our recommendation is therefore an application of this structure to participating academic institutions throughout Switzerland. and to include the governmental agencies, and participating industries.

SWISSTOX should provide the following items or services:

Collaboration: encourage interactions and collaborative projects between the Universities and the two Swiss Federal Institutes of Technology, the industry and the governmental agencies with respect to research on xenobiotics.

Education: provide adequate integrated training programs for toxicologists, at the undergraduate, doctoral and post-graduate level

Service function : providing toxicological data for the governmental agencies and industry.

Public relations: communication of issues about toxicological matters to the public.

Link across national borders: maintain and establish new links with toxicological centers in European countries and with international societies.

Actions to be taken

As a first step, we recommend that a steering committee be formed. The Academies, the SSPT, the Swiss Science Council and the Group for Science and Research should be represented in this committee. The initial task of this committee is to put forward a concrete plan of action to create SWISSTOX, if they are in general agreement with the above recommendations.

The steering committee should elaborate a concise proposal regarding the structure, the mission, the financing, and the time-frame of SWISSTOX.

At a later stage, an advisory panel of toxicological experts should be created that will identify the strengths and weaknesses of the groups participating in SWISSTOX. It also will be responsible for the definition of future strategies, priorities and directions of toxicology oriented research, education and services in Switzerland.

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