3R Research Foundation Switzerland / 3R Info Bulletins / Gerhard Zbinden and 3R

Gerhard Zbinden was born in 1924. After a completing Medical School at the University of Berne in Switzerland, he moved to Basle and later to the USA, where he held important positions at F. Hoffmann-La Roche, first as a scientist in the Department of Experimental Medicine and subsequently as Director of Biological Research.

At forty years of age he was nominated to Director of Research and Vice President of the Research Division of Hoffmann-La Roche Inc. at Nutley, NJ. He played a key role in the development of several important and successful agents including vitamins, drugs used in psychiatry and agents to treat infectious diseases.

In 1967 Gerhard Zbinden moved to Cambridge (UK) to become a research associate at the University of Cambridge.

In 1970 he began a second career in Switzerland, first as Professor of Experimental Pathology at the University of Zurich and 1975 as Professor and Director of the Institute of Toxicology of both Universities, the Swiss Federal Institute of Technology and the University of Zurich.

Known and respected worldwide as a leading scientist and teacher in the field of toxicology, Gerhard Zbinden retired in 1991.

In addition to professional commitments, Gerhard Zbinden played an active role in advising national and international bodies, among them the NIH, WHO, FAO/WHO, Ministry of Research and Technology FRG in the Expert Group for Alternative Methods in Animal Experimentation, etc.

Professor Gerhard Zbinden died in September 1993, shortly after his 69th birthday.

Gerhard Zbinden and 3R

"To make a new drug you need chemists. . . and many other '. . .ists' and lots of luck. But the most precious commodity is time, the only thing that money cannot buy. You hear the clock ticking constantly. . ."

The scientific commitment of Gerhard Zbinden

Gerhard Zbinden's commitment was dedicated to making scientifically based and ethically responsible decisions in toxicology for the broader benefit of society, animals and research in chemistry.

Ethical considerations in toxicology

According to Gerhard Zbinden, the toxicologist has special responsibilities. Toxicologists should pause from time to time to contemplate their activities critically and to review past achievements. Keeping in mind the fantastic progress that has been made in the biomedical sciences, toxicologists have to consider carefully their routine experimental procedures and ask themselves in light of newer methods in alternatives to animal experimentation whether they really get the best, the most comprehensive and most relevant information from each animal they use in the name of human safety.

Over the last 30-40 years, society's demands for safety have led to an escalation in costs, in the use of animals, and demands on highly skilled personnel in toxicology. The desire to detect even the slightest undesirable effect has led to the use of large numbers of laboratory animals, and to the application of very high doses to some of the animals.

If toxicologists are not convinced of the value of a procedure, they have an obligation to make their doubts known. They are obligated to initiate well-directed research programmes, and to press for revision of regulatory requirements if their investigations demonstrate that new methodological approaches can provide more relevant results.

The concept of multispecies testing reviewed

Flying in the wind of the most common recommendation of many guidelines to use the rat as the rodent and the dog as the representative nonrodent animal to predict toxicity in humans, Gerhard Zbinden showed that multispecies testing in animals is useful only in very exceptional cases. In a project supported by the Foundation Research 3R, he recommended that a second species (usually the beagle dog) should not be automatically required in the protocols for acute and repeated-dose toxicity testing.

At the International Workshop on Use and Misuse of the Dog in Experimental Toxicology 1992 in Zurich, Gerhard Zbinden criticised the historically derived tendency to use automatic the dog, mainly the beagle, as nonrodent species in the risk assessment of drugs and other chemicals.

In the past few years he developed several techniques to detect relevant differences in metabolic pathways of test chemicals in dog, humans and other mammalian species using in vitro procedures and short-term in vivo pilot experiments.

Gerhard Zbinden made a difference

Gerhard Zbinden is known throughout the world, not only for his work as a toxicologist, but also for his efforts towards animal protection: "He translated the 3R's of Russell and Burch into the language of the toxicologist" said one of the leading protagonists of animal welfare, Alan M. Goldberg, Director of the Center for Alternatives to Animal Testing, Baltimore, USA.

Prof. Zbinden and Animal Welfare in Switzerland

From 1982-1988, Gerhard Zbinden was an active and critical member of the Swiss Federal Committee for Animal Experimentation, which advises the Federal Veterinary Office on questions of animal welfare.

As a member of the Expert Committee of the Swiss Academy of the Medical and Natural Sciences he co-authored "Ethical Principles and Guidelines for Scientific Experiments on Animals" in 1983.

From 1985 until his death he was chairman of the "Hildegard Doerenkamp/Gerhard Zbinden Stiftung, realistic animal protection in bio-medical research", which supports the search for alternative experimental methods, especially in the domain of large animals.

In 1986, on behalf of the Swiss Federal Veterinary Office, Gerhard Zbinden actively promoted the revision of the OECD Guidelines for Testing of Chemicals 401.

The success of Gerhard Zbinden's contribution to animal welfare are attributable to his scientific competence, his critical attitude towards his own field of research, his courage in expressing "uncomfortable" facts and his readiness to and talent for popularizing science. His criticism of the misuse of the LD50-test is well known.

With the death of Gerhard Zbinden, the Foundation Research 3R lost the very appreciated leader of an outstanding 3R project. Science and animal welfare community lost a valued proponent of the concepts of the 3R's.

Recommendations for further reading

"Menschen, Tiere und Chemie" is a comprehensive book on toxicology written by Gerhard Zbinden in 1985 for laymen, scientists, animal welfarists, politicians and authorities. This book gives an overview on problems and questions in toxicology, using more than 100 examples of substances, their effects and their testing as illustrations. The toxicological methods of today are compared with the modern experimental toxicological methods of tomorrow.

Gerhard Zbinden was a highly sensitive and creative man, a keen observer of human nature with the gift of being able to laugh at his and others' faibles. In his last book, "The Source of the River Po", he gives a refreshing, lively, instructive and self-critical description of winning, losing and high living in drug research. "The book is about. . . the men and women involved in inventing, developing and selling new drugs, beginning with Andy Zoller whose job is similar to the one I once struggled to fill as hard as he does".

Short Selection of References

Zbinden G, 1993, The Source of the River Po: winning, losing and high living in drug research. Frankfurt am Main, Haag + Herchen GmbH. ISBN 3-89228-908-5.

Zbinden G, 1993, The concept of multispecies testing in industrial toxicology. Paper presented at the International Workshop on Use and Misuse of the Dog in Experimental Toxicology, Oct. 19-20, 1992, Zurich. Regul Toxicol Pharmacol 17, 85-94.

Zbinden G, (ed), 1992, The brain in bits and pieces: International workshop on the application of in vitro methods in neurobiology, neurotoxicology and neuropharmacology, Dec 14, 1990. Zollikon, M T C. ISBN 3-907-03703-0.

Zbinden G, 1991, Predictive value of animal studies in toxicology. Regul Toxicol Pharmacol 14,167-177

Alder S, Zbinden G, 1988, National and international drug safety guidelines. Zollikon, M T C. ISBN 3-907-03702-2.

Zbinden G, 1985, Menschen, Tiere und Chemie. Zollikon, M T C. ISBN 3-907-03701-4.

Zbinden G, 1985, Ethical considerations in toxicology. Fd Chem Toxicol 23, 2, 137-138.

Zbinden G et al. (eds), 1983, Current problems in drug toxicology. Paris, Libbey. ISBN 0-86196-030-0.

Zbinden G, Flury-Roversi M, 1981, Significance of the LD50-test for the toxicological evaluation of chemical substances, Arch Toxicol 47, 77-99.

Zbinden G, Gross F, 1979, Pharmacological methods in toxicology. Oxford, Pergamon Press. ISBN 0-08-024900-0.

Zbinden G, 1973, Progress in toxicology. Berlin, Springer. ISBN 0-387-06495-8.

Further Information:

The publication list of Gerhard Zbinden (313 publications) from various databases (Medline, Toxline, Biosis, Chem and Sci Search) can be ordered from the scientific staff of the Foundation.

Hildegard Doerenkamp / Gerhard Zbinden Stiftung. Chairman: Prof. B. Gähwiler, Brain Research Institute, University of Zurich, August Forel Str. 1, P. O. Box, 8029 Zurich, Switzerland.

3R-INFO-BULLETIN 3 - December 1994