11th Greek Australian Legal and Medical Conference
Crete, Greece 2007

The Ethics of Animal Use in Biomedical Research

Assoc. Professor Ismene A. Dontas DVM, PhD

Introduction – a glimpse through history regarding animals used in research

Animals have been used since antiquity to acquire knowledge of the anatomy and physiology of the human body, as well as to gain understanding of diseases. The first recorded use of animals for research purposes was during the 4th and 3rd centuries B.C., by Aristotle of Greece and Erasistratus of Alexandria respectively. Later, in the 2nd century, the physician Galen of Pergamon used apes, cows, dogs and pigs to investigate the anatomy and physiology of the respiratory system, kidneys, heart and vessels. In spite of several medical misconceptions due to animal, rather than human dissection, he remained an unchallenged medical authority for over a thousand years.1, 2 The Renaissance was a period of renewed interest in biomedical research. From the 16th to the 18th century, animal experiments were conducted by several well-known scholars, such as Andreas Vesalius, Francis Bacon, William Harvey, René Descartes and Stephen Hales. During this period, the notion that animals are incapable of feeling pain prevailed. It was not until the nineteenth century, mainly in England and France, that public concern of animal suffering and ethical arguments appeared. Although the physiologists François Magendie and Claude Bernard conducted their impermissible by today’s standards animal experiments in France, the antivivisection movement started in England. In 1871, the British scientific community was the first to issue recommendations concerning animal experiments, requiring the use of anaesthetics and generally taking into account their welfare. The first legislation in the world to regulate the use of animals in research, the 1876 Cruelty to Animals Act, also originated in England. In contrast, it was not until 1963 that the first French legislation controlling animal experiments was passed.3

During the beginning of the 20th century, progress in physiology and medicine was achieved mainly through animal research, partly demonstrated by the amount of scientists awarded Nobel Prizes for their discoveries using animals. As an example, Ivan P. Pavlov was awarded the 1904 Nobel Prize for his work on the physiology of digestion, carried out on dogs. He also became famous for his work on conditioned reflexes, also on dogs. Another example is the discovery of insulin, for which research was conducted on dogs, and Frederick G. Banting and John J. R. Macleod jointly received the 1923 Nobel Prize in Physiology or Medicine.4

Recent research using animals

The discoveries resulting from research using animals, especially during the 20th century, contributed to the increase of life expectancy from approximately 45 years in the early 1900s, to 79 years in 2000, in developed countries. The 20th century was witness to the emerging of “Laboratory Animal Science”: the scientifically, legally and ethically accepted study and use of animals for biomedical aims, as well as the scientific use of different animal species, as models for the study of man or other animals, and their diseases. This scientific area is continuously growing, with new information on all aspects of laboratory animals’ care and use, including the education and training of people coming into contact with them on all levels, their health monitoring, etc.5,6,7,8 With this information, researchers have the possibility of optimizing animal welfare, while simultaneously safeguarding their scientific results. The term “animal model” emerged as well: an animal model for a disease is the animal, in which a spontaneous or induced pathological condition can be studied, and which is similar, to a lesser or greater degree, with the same condition in man. Rodents are the class of animals in which the largest number of animal models have been and are still being developed.

Apart from the guides and recommendations on the scientific issues concerning laboratory animals, their use is controlled by international, national and establishment regulations. In the European Union (EU), for example, experiments on animals are subject to the Directive 86/609/EEC on the “protection of animals used for experimental and other scientific purposes”9. All member states are required to have in place national legislation, which transposes at least the minimum requirements laid down in the Directive. The Directive is currently being revised, to include updated and new aspects of scientific knowledge and experience, with emphasis on animal welfare. In the meantime, the Council of Europe’s Convention ETS 123 for the “protection of vertebrate animals used for experimental and other scientific purposes” agreed in 1986, has recently revised the Appendix A of the Convention, which includes housing and care guidelines, taking into account additional species used, new caging dimensions, the specific needs of the different species, the need for environmental enrichment, the social composition of groups and the different use of the animals (breeding, research, etc.).10 The revised Appendix A entered into force on June 15, 2007. It constitutes a significant step towards the optimal ethical and scientific use of laboratory animals in research.

Establishment regulations also have a very important role in safeguarding the ethical use of research animals. They are usually set down, in addition to national legislation, by the establishment’s Ethics Committee or the Institutional Animal Care and Use Committee. These committees are responsible for the initial ethical evaluation of research projects that plan to use laboratory animals and to ensure animal welfare considerations are applied.

The latest report of the numbers of animals used indicatively in the EU in 2002 shows a decline in the percentage of rodents and rabbits used in comparison to 1999 (78% compared to 87% in 1999) and an increase in the use of cold-blooded animals (15.4% compared to 6.6% in 1999). Of all the animals used in 2002 (10.7 million), 85.5% was used for the study of human diseases and the remaining percentage for animal diseases.11

Laboratory animal scientists are striving to apply wherever possible the three Rs that Russell and Burch first mentioned in 1959: reduction, replacement and refinement of animal use, also called “alternatives to animal use”.12 There are many valid alternative methods today to the use of live animals and the many databases and electronic technology assist in their being disseminated and applied. Replacement methods include in vitro techniques, audiovisual material and slaughterhouse material. Reduction methods include pilot studies, better design and statistical evaluation of experimental study, choosing the most appropriate animal model and cooperation between scientists. Refinement of experimental procedures to lessen pain, suffering and distress, and to enhance animal well-being includes optimal animal care, skilled persons performing the study, the knowledgeable use of anaesthesia, analgesia and euthanasia, telemetry, non-invasive procedures and environmental enrichment. Environmental enrichment is any modification in the environment of the captive animal that seeks to enhance its psychological and physiological well-being by providing stimuli, meeting the animal’s species-specific needs.

It is to be hoped that, with the development of specific animal models of human diseases, genetically modified animals that have virtually no variation and valid alternative methods to animal experiments and in spite of the need to find therapies for chronic human diseases, the numbers of animals used in biomedical research will decrease, with a concomitant enhancement of their welfare.

Ethical debate on animal use in research

Animal experimentation has become a legally limited and accepted method of scientific inquiry. However, it continues to be a debated issue. Both its advocates and its opponents have many and complex arguments, not within the scope of this article.

Public concern for animals’ quality of life is increasing and the right to use them is questioned, in parallel to the increasing need to find therapies for human diseases. The key questions to be addressed for a compromise to be found are:

Is their use ethically evaluated and monitored adequately?

Is everything humanely possible being done, to keep the negative effects on them to a minimum and to enhance their welfare?

Can their “harm” (the cost to the individual animal in terms of suffering, pain and distress) be justifiably counterbalanced by the “benefits” (to humans, animals or the environment) emerging from this research?

If these questions had clear-cut positive objective answers, perhaps the debate would have ended. To quote F. Barbara Orlans: “Agreement on ethical principles to guide animal experimentation is still a long way off.”3

References

  1. Aristotle and Barnes J. The Complete Works of Aristotle: the revised Oxford translation. J. Barnes, editor, vol. 1, Bolligen Series, 1995.
  2. Eknoyan G and Nagy J. A history of diabetes mellitus or how a disease of the kidneys evolved into a kidney disease. Advances in Chronic Kidney Disease 12: 223-229, 2005.
  3. Orlans FB. In the name of science. Issues in responsible animal experimentation. Oxford University Press, New York, 1993.
  4. http://nobelprize.org/nobel_prizes/medicine/laureates/
  5. Institute of Laboratory Animal Research (ILAR), National Research Council. Guide for the Care and Use of Laboratory Animals, 1996.
  6. Wilson MS, Berge E, Maess J, Mahouy G, Natoff I, Nevalainen T, van Zutphen LF, Zaninelli P. FELASA recommendations on the education and training of persons working with laboratory animals: categories A and C. Laboratory Animals 29: 21-131, 1995.
  7. Nevalainen T, Dontas I, Forslid A, Howard BR, Klusa V, Kasermann HP, Melloni E, Nebendahl K, Stafleu FR, Vergara P, Verstegen J. FELASA recommendations on the education and training of persons carrying out animal experiments (Category B). Laboratory Animals 34: 229-235, 2000.
  8. Nicklas W, Baneux P, Boot R, Decelle T, Deeny AA, Fumanelli M, Illgen-Wilcke B. Recommendations for the health monitoring of rodent and rabbit colonies in breeding and experimental units. Laboratory Animals 36: 20-42, 2002.
  9. Directive 86/609/EEC, OJ L 358, 18.12.1986. http://europa.eu.int/environment/chemicals/lab_animals/revision_en.htm
  10. Revised Appendix A of the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes ETS 123: http://conventions.coe.int/treaty/en/Treaties/html/123/htm
  11. Commission of the European Communities. Report from the Commission to the Council and the European Parliament. Fourth report on the statistics on the number of animals used for experimental and other scientific purposes in the Member States of the European Union. Brussels, COM(2005) 7 final, 20.1.2005.
  12. Russell WMS and Burch RL. The Principles of Humane Experimental Technique. Methuen, 1959.