1. 1. 1. Introduction and key concepts
         Laboratory animal science emerged as a field only in the late 40s even though animals were used in research experiments over centuries. Quality of care for the animals varied widely depending on individual researchers and institutions. Lack of guidelines and standards became a growing concern for veterinarians, animal care personnel and responsible researchers who feel that have a moral obligation to provide care and ensure welfare for animals used for studies.Thanks to animal experiments modern medicine has made highly beneficial advances discovering insulin and antibiotics, developing vaccines, treatment for cancer and other diseases. As a result, both humans and animals have longer and healthier lives than in previous generations.However, animal research is a controversial issue. Most people, recognize that biomedical research made the vital contribution towards improving health and welfare of humans and animals. But there are many activists who oppose animal research, lead protest demonstrations and sometime even go to vandalism.Scientists increase use of alternatives to animals, such as computer models or cell culture techniques. Better understanding of statistical methods makes possible to use fewer animals to obtain scientifically valid results. Regulations and guidelines have been developed to ensure ethical and humane manner of using animals in research.Bioethics is the study of ethical, social, and legal issues that arise in biomedicine and biomedical research. One of the important issues in bioethics is how to maintain a balance between using animals for research and the benefits that animal experiments can bring. Biomedical research should adhere the following main principles:
         • Use of animals in research should be scientifically relevant and justified
         • Physical and psychological well-being of animals in research studies should be maintained as much as possible
         • Pain, suffering, distress or lasting harm to the animals should be avoided or minimized. If an animal’s severe pain cannot be relieved, the animal should be humanely euthanized

3R concept

3Rs concept was developed by the zoologist William Russell and the microbiologist Rex Buch in 1950s and described in their book “The Principles of Humane Experimental Technique”, published in 1959. Since then, this concept has been embedded in national and international legislation and regulations on the use of animals in scientific procedures, as well as in the policies of organizations that fund or conduct animal research.

The Orbeli Institute of Physiology is committed to comply with the internationally accepted approach of Three Rs for the implementation of the principles of humane care and use to guide Institute’s animal research.

Replacement refers to methods which avoid or replace using animals. This includes absolute replacements (i.e., replacing animals with computer models) as well as relative replacements (i.e., replacing vertebrates with animals having a lower potential for pain perception, such as some invertebrates).

Wherever possible, a scientifically satisfactory method or testing strategy, not entailing the use of live animals will be used in the Institute instead of a procedure.

Reduction refers to the strategy for obtaining sufficient data using fewer animals or for maximizing the information obtained per animal (without increasing pain or dis­tress) and thus potentially reducing number of animals needed to acquire the same scientific information. This approach relies on experimental design and appropriate statisti­cal methods, application of new technologies. Sharing the data or other materials obtained with other research groups contributes to reduction. A number of journals allow the raw data from published studies to be provided on-line, there are also available free scientific data repositories (e.g. https://datadryad.org or https://figshare.com). The Institute will take efforts to reduce to a minimum number of animals used in the projects without compromising the scientific objectives.

Refinement refers to modifications of husbandry or experimental pro­cedures to minimize or eliminate pain and distress, and to enhance the welfare of animals used in science. Careful study design as well as determination and application of humane endpoints help to reduce the duration of pain and distress. More information and examples can be found at the website page site “Humane endpoints in laboratory animal experimentation”. The Institute will ensure refinement of methods used in procedures eliminating or reducing to the minimum any possible pain, suffering, distress or lasting harm to the animals.

Please, visit https://learn.etplas.eu/all-courses/ and register for free training module EU12, The Severity Assessment Framework.

Refinement and reduction goals should be balanced on a case-by-case basis. Principal investigators are strongly discouraged from advocating ani­mal reuse as a reduction strategy, and reduction should not be a rationale for reusing an animal that have already undergone experimental procedures especially if the well-being of the animal would be compro­mised.

Studies that may result in severe or chronic pain or significant harm in the animals’ normal physiology should include descriptions of humane endpoints or provide science-based justification for not using a humane endpoint.

Death as the end point of the procedure shall be avoided as far as possible and replaced by early and humane end-points. Where death as the end-point is unavoidable, the procedure shall be designed so as to:

1. Result in the deaths of as few animals as possible
2. Reduce the duration and intensity of suffering of the animal to the minimum possible and, as far as possible, ensure a painless death.

While researchers should take all reasonable measures to eliminate pain and distress through refinement, IACUC members should understand that certain type of studies may have unforeseen or intended experimental outcomes that produce pain. These outcomes may or may not be eliminated depending on the research goals. When pain or distress is beyond the level anticipated in the protocol descrip­tion the veterinary consultation must occur.

Regulations, policies and principles

The L.A. Orbeli Institute of Physiology is committed to ensure proper animal care and use, training of the staff, careful planning of experiments, and taking all efforts to mitigate pain and distress for the animals. Our animal care and use (ACU) program comprises all activities that have a direct impact on the animals’ welfare, including animal and veterinary care, policies and procedures, personnel management, occupational health and safety, IACUC functions, animal facility design and management.

In Armenia the use of laboratory animals is governed by the regulatory requirements outlined in the Article 11 of the Republic of Armenia Law about veterinarian care approved on June 21, 2014. To comply with the Directive 2010/63/EU of the European Parliament and of the Council on the protection of animals used for scientific purposes and the European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes, the Orbeli Institute’s Animal Care and Use Program endorse the following principles:

• Use of animals in procedures should be restricted to areas which may ultimately benefit human or animal health, or the environment
• Consideration of alternatives (in vitro systems, computer simulations or mathematical models) to reduce or replace the use of live animals wherever possible
• Selection of methods that will use the minimum number of animals without compromising the objectives of the project and providing reliable results
• Selection of species with the lowest capacity to experience pain, suffering, distress or lasting harm
• Avoidance or minimization of any possible pain, suffering, distress or lasting harm to the animals
• Use of appropriate sedation, analgesia and anesthesia
• Selection of methods that avoid as far as possible death as an end-point due to the severe suffering experienced during the period before death
• Establishment of humane endpoints
• Use of appropriate methods of animal sacrifice if death is unavoidable as the end-point and, as far as possible, ensuring painless death
• Sharing tissues and organs of animals that are sacrificed to reduce number of animals used
• Provision of adequate veterinary care
• Provision of appropriate animal transportation and husbandry directed and performed by qualified personnel
• Conduct procedures on living animals exclusively by and/or under the close supervision of experienced personnel
• Refinement of breeding, accommodation and care
• Refinement of methods used in procedures, eliminating or reducing to the minimum possible pain, suffering, distress or lasting harm to the animals

In November 2023, the Animal Care and Use manual has been developed to provide information to assist personnel, researchers, IACUC members and other stakeholders in the implementation of effective and appropriate animal care and use in line with the Directive 2010/63/EU of the European Parliament and of the Council and European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes. Institutional Animal Care and Use Committee (IACUC) has been established in May 2024 to oversee and routinely evaluate care and use of laboratory animals for research activities.