Ethics and Care of Experimental Animal Rianto SetiabudyLecture for the Regular and International Classes, FMUI Jakarta, 3 Dec. 2008

IntroductionAnimal experimentation is fundamental to the biomedical sciences, i.e.:PreventionDiagnosisfor man and animal as wellTreatment Potency and safety testing of biological substancesThe International Guiding Principles for Biomedical Research Involving Animals was developed by the Council for International Organization of Medical Sciences (CIOMS) in 1985 after 3-year international consultation between experts

Examples of major medical advances based on research using animals1600:discovery of blood circulation1700: measurement of blood pressure1800: vaccination1920: discovery of vitamins and insulin1950: kidney transplants1960: heart transplants, coronary by-pass operation1980: CT scan, antiviral drugs1990: gene therapy for cystic fibrosis

The ObjectivesTo understand the International Guiding Principles for Biomedical Research Involving Animals developed by the Council for International Organization of Medical Sciences (CIOMS)To understand the ethical aspects of the procedures commonly applied to experimental animals

The International Guiding Principles for Biomedical Research Involving Animals1. Basic principles

The advancement of biological knowledge development of improved means for the protection of health and well-being of man and animals require recourse to experimentation on intact live animals of a wide variety of species. Mathematical model, computer simulation, and in- vitro biological systems should be used wherever possibleAnimal experimentation can only be done after due consideration of their relevance for human and animal health and the advancement of biological knowledgeThe animal selected for experimentation should be of an appropriate species and quality. Minimum number to obtain scientifically valid result should be used.

Investigators should always remember that animals are sentient. Investigators should provide proper care, avoid/minimize discomfort, distress, and painInvestigator should assume that all painful procedures in human being are also painful to other vertebrate speciesAll procedures that cause more than momentary or minimal pain should be performed with appropriate sedation, analgesia, or anesthesia. Surgical or other painful procedures should not be performed on animals just paralized by drugs, but without anesthesia

Decision on Articles 4-7 should not rest solely with the investigators, but by a suitably constituted review bodyAt the end of an experiment, animals that suffer from severe or chronic pain, distress, discomfort, or disablement that cannot be relieved, should be painlessly killed. If appropriate, they even have to be killed during the experimentAnimals used for biomedical experiment must be provided with the best possible living conditions. The care of these animals should be under the supervision of veterinarians experienced in laboratory animal science.

The director of an institution using experimental animals must be responsible to ensure that investigators and personnel have appropriate qualifications or experience for conducting procedures on animals. They should be given in-service training, including the proper and humane concern for the animals under their care

2. Special provision

2.1 Acquisition:The best source of experimental animals is from the specialized breeding establishmentsNonspecifically bred animals may be used only if they meet the research requirements, particularly for health and qualityTheir acquisition should not in contradiction with national legislation and conservation policies2.2 Transportation:The director of the research institution should emphasize to the supplier and carrier that the animals should be transported under humane and hygiene conditions

2.3 Housing: Animal housing should be such as to:ensure general health to the animalsavoid undue stressbe large enough for each animal (according to the species)be free from predators, vermin, other pestsFacilities for quarantine and isolation should be available and unauthorized persons should not be allowed to enter the housing area.

2.4 Environmental condition: Temperature, humidity, ventilation, lighting should be consistent with the species concernedNoise and odor level should be minimal.Facilities should be provided for the disposal of animal waste.

2.5 Nutrition:Free access to potable water and foodFood quality and quantity should be sufficient to preserve the animals health2.6 Veterinary care:animal health surveillance and disease prevention should be made availablesick or injured animal should receive appropriate veterinary care or be painlessly killed2.7 Records:Records for all experiments in animals should be available for inspection. Information should include various procedures carried out and post mortem examinations (if conducted)

3. Monitoring the care and use of animals

3.1 Wherever animals are use for biomedical purpose, their care and use should be subject to the general principles and criteria set out above as well as to existing national policies. The observance of such principles and criteria should be assured by independent monitoring3.2. The objectives of monitoring and the principles are: to avoid excessive or inappropriate use of experimental animalsto encourage appropriate care and use before, during, or after experimentation. This can be established by:Specific legislation laying down standardsEnforcement by official inspectionSelf-regulation by the biomedical community

4. Methods not involving animals: Alternatives

4.1. Alternatives means:replacement of the use of higher to lower animals. This means, if possible, the use of warm-blood animals should be replaced by micro organism, plants, eggs, reptiles, amphibians, and invertebrates. Alternately, live animals may be replaced by non-animal models such as computer models or audiovisual aids

methods that lead to a reduction of the number of animals required for the experiment. Methods to achieve this include:Pilot studiesUsing animals as their own controlCollecting a maximum information from each animalConsultation to a statisticianMinimizing disease, stress, diet, geneticsAvoid duplicationUse appropriate species

refinement of experimental procedure means minimizing pain or distress whenever possible. Examples of refinement include:Identify pain and distress and prevent or relieve itSet earliest endpointAdequate training prior to performing a procedureApply proper handling techniques for animalUse correct dose and ensure the drug is not yet expired

Ensure the procedures are reasonable for that speciesUse appropriate analgesics and anesthetics for potentially painful proceduresApply aseptic procedure for surgeriesPerform only a single major survival surgery on any one animal whenever possiblePerform appropriate post surgical care (thermoregulation, fluid balance, etc)

Note: this is commonly referred to as the 3Rs principles

4.2.Alternative procedures include:non-biological methods: mathematical modeling of structure activity relationships based on the physical properties of the drugs, computer modeling of other biological processesbiological methods: microorganism, in-vitro preparations (subcellular fractions, whole organ perfusion, cell and organ culture, invertebrate and vertebrate embryos)4.3. The adoption of alternative approach is viewed as being complementary to the use of intact animals and their use should be actively encourage for scientific and humane reasons

The ethical aspects of the procedures commonly applied toexperimental animals

1. Physical intervention a. Restrain:Restrain means the use of hands, tools, or drugs to limit the normal movement of animal for the purpose of research, examination, taking biological samples, or therapyEnsure that the procedure does not cause injury or reduce the comfort of the animalsAvoid prolonged restrain to the animals b. Limitation of access to food and water:If a reduction of food and drinking water is needed to meet the objective of the experiment, the reduction should not affect the normal growth and the long term health of the animals.The reason to limit food and drink for the animals should be scientifically sound

2. Behavioral intervention:Experimental animals should be treated in accordance to its biological speciesCommunal animals need social communication with its species the construction of the cage should allow the animal to have visual, auditorial, and olfactorial contact with its fellow speciesFor territorial animals, the presence of other animals in its territory may induce stressThe presence of 2 or more animals of different species in one cage may also induce stress

3. Surgery:Types of surgery in experimental animal:Survival (animals are expected to recover after surgery):MajorMinorTerminal (animals are killed before they recover from anesthesia)Major survival surgeries open body spaces (e.g. laparotomy, thoracotomy, craniotomy) and joint replacement:Not more than once in each animalShould be better performed by veterinarians

Minor survival surgeries do not open body spacesMinor, terminal, and major survival surgeries in rodents should be performed by veterinarians or other experienced personsPre-surgical measures include: physical examinations, vital signs, fasting, administration of sedatives and other premedicationsAll surgical measures in animals should be done aseptically

4. Post-surgical care:In post-surgical recovery stage, the animals should be:put under intensive care of experienced personsplaced separately from other animalskept in fasting as long as they have not recover from anesthesia

5. Experimental procedure:All experimental procedures in animal should be done by experienced personsIntensive observations on complications or side effects associated by invasive experimental procedures should be done by the veterinarians

6. Pain:In general, all procedures that induce pain in human being should be assume capable of inducing the same effect in animalsDuring an experiment, all animals known to suffer from distress or pain which cannot be relieved by drugs or other measures, which leads to poor prognosis, may be withdrawn from the study and killed by a professional veterinarian with an advance notice to the investigator7. Anesthesia and analgesia:All experimental procedures that induce more than a momentary pain should be preceded by administration of anesthetics or analgesics, unless it can be proven scientifically that this agents will influence the result of the experiment

The choice of anesthetics or analgesics is under the discretion of the veterinariansAll painful procedures in animals, should not be treated with sedative, anxiolytics, or neuromuscular blocking agents alone without anesthetic or analgesic agents

8. Euthanasia:This means a procedure to rapidly and painlessly kill an unconscious experimental animal This procedure can only be done by professionals who are experienced in animal killing methods and death confirmationThis procedure is to be done in a place separated from other living animals

9. The use of animal fetus:Animal fetuses that cannot grow up to become a normal and self-sustainable animal as a result of experimentation should be immediately killed after birthIf a procedure is done on an animal fetus after the implantation stadium, then it should be treated similarly to adult animals especially in terms of pain relieving.

10. The use of endangered species:Endangered species of animals can only be used for experimentation with the consent of the authorized agency

11. Sending and receiving animals to and from a foreign country:This can be done for the research purpose in accordance to the local and international regulations

Thank you