Introduction

By law, animals in federally-supported research centers are provided with humane living conditions that are less stressful than the daily struggle for survival that animals face in the wild. In the laboratory, appropriate food, housing, and veterinary care are provided. Pain and stress--when necessary in specific research, (i.e., to develop new pain-killing drugs)--are kept to the absolute minimum.

Even if Federal and Provincial/State laws and policies did not mandate humane treatment of animals, the requirements of science itself would still make it necessary. Scientists simply cannot use animals in research that are not healthy and properly cared for.   Illness, undue stress, or poor living conditions would interfere with obtaining valid, useful results from scientific experiments using animals. Excellent science requires excellent animal care.

Ethics and Animal Use in Research

Dr. M.M.S. Bailey, D.V.M.

Animal Investigation:

When using animals in research, teaching or testing, we ascribe to the "Ethics of Animal Investigation," a document published by the Canadian Council on Animal Care (CCAC).

The use of animals in research, teaching and testing is acceptable only if it promises to contribute to the understanding of fundamental biological principles or to the development of knowledge that can reasonably be expected to benefit humans or animals. Researchers must have diligently sought alternatives before requesting to use animals, and the smallest number of the most appropriate animals must be used.

The "3R's" of Animal Use:

• Reduction refers to the use of fewer animals to obtain the same amount of information
• Refinement means alteration of existing procedures to minimize the discomfort they cause to the animals.
• Replacement means the use of research methods or models that do not use animals instead of models that do.

It is imperative that studies be well thought out in advance. Studies must include the appropriate control groups and numbers of animals to assure that the data can be interpreted with statistical confidence. If too few animals or inappropriate control groups are used, the data may be worthless. It is equally inappropriate to use more animals than is absolutely necessary. It is not appropriate to request extra animals "for practice," or "just in case there are problems."

If unexpected problems occur, a veterinarian should be consulted. The problems should be clarified and corrected; i.e., intercurrent disease or problems with the techniques.

It is inappropriate to practice techniques on experimental animals. Techniques should be learned from experienced people through instruction, observation and practice on euthanized animals. Practicing techniques on experimental animals is not only stressful to the animals, but can affect the experimental outcomes.

Appropriate animal models should be used for the disease or treatment being studied.

Procedures using animals must be refined to ensure that the most humane methods are used, to ensure minimal stress to the animals. Cost and convenience must not take precedence over the animal's physical and mental well-being.

Animals must not be subjected to unnecessary pain or distress. Appropriate aesthetics and analgesics (pain killers) must be used. Experiments that withhold analgesics must be closely evaluated for scientific merit.

When we use animals, we are obliged to provide not only for their physical comfort, but for their behavioral or psychological well-being.

There are two components of well-being: physical and behavioral. Physical well-being is manifested by clinical health. Behavioral well-being is manifested by behaviour considered to be normal for that species and strain, and by the lack of significantly abnormal behaviour. Behavioral well-being is said to reflect psychological well-being.

A social environment should be provided, if appropriate for the animals. Groups must be stable. Frequent regrouping can be detrimental, as the social hierarchy must be re-established each time, increasing aggressive interactions.

Caging should be enriched appropriately. Enrichment is the provision of items with which the animal can interact, to provide for such activities as hiding, foraging or burrowing.

It is imperative that researchers understand the species and strain of animal that they are working with. They must know the normal behaviour for their animals. It is impossible to provide the optimal environment and appropriate enrichment if one does not know what is normal for that animal. One must also know what is normal in order to recognize the abnormal.

Basic needs include an appropriate environment (temperature, ventilation, humidity, light cycle, food, water, caging, noise levels). The amount of space should be appropriate to the species, but more is not necessarily better.

The Regulations Governing Animal Use:

Criminal Code of Canada:

• The Criminal Code of Canada, Cruelty to Animals Section, forbids "causing unnecessary suffering." It is an offence to willfully cause, or - being an owner - willfully permit to be caused unnecessary pain, suffering or injury to an animal or bird. Scientific research is exempt unless the risk of injury or serious physical pain are disproportionate to the expected benefit from the research.

Canadian Council on Animal Care:

• The Canadian Council on Animal Care (CCAC) is a national peer-review organization (as opposed to legislation). The CCAC is co-funded by the Medical Research Council (MRC) and the Natural Sciences and Engineering Research Council (NSERC). It has twenty member organizations made up of scientists, educators, industry representatives, and animal welfare representatives.
• The mandate of the CCAC is to work for the improvement of animal care and use on a Canada-wide basis.
• CCAC assessment panels evaluate animal care and use in Canadian universities and community colleges, government laboratories, and commercial laboratories. An in-depth site visit is performed every three years. Follow-up visits may be made, announced or unannounced.
• Assessment panels are made up of three or more scientists, an animal welfare representative, and the CCAC Director or Associate Director of Assessments. These assessment panels make recommendations to improve the care and use of animals.
• If institutions are found to be in non-compliance with CCAC guidelines, all granting agencies and relevant government ministries and departments are notified. Non-compliance will jeopardize research funds.

The Animals for Research Act:

• This legislation deals with the procurement and/or use of laboratory animals. The Act is complementary with the CCAC.
• The Act requires the annual registration of all research facilities in Ontario.
• The Act requires the use of anaesthetics and analgesics to prevent unnecessary pain and suffering in the animals.
• Although the Animals for Research Act is complementary with the CCAC, it is important to distinguish a very important difference. The Act regulates the minimum standards for animal housing, procedures and care, whereas the CCAC guidelines strive for the "optimal" conditions and are ever changing as new information becomes available.
• OMAF inspectors conduct unannounced inspections of any premises on which animals used in research are maintained. This includes not only animal quarters, but the laboratories and procedure rooms where animals are used.
• The inspectors look at the housing of animals; the facilities (floors, walls, doors, windows, lights, etc.); water, food, type and size of caging; temperature, humidity and ventilation; cleanliness; animal identification; animal records; health programs; animal use protocols; the use of anesthesia and analgesia; and the methods of euthanasia and disposal.
• If animal care or use does not meet the standards as laid out in the Animals for Research Act, the inspectors can recommend hearings to refuse, refuse to renew, or revoke the facility registration. This would make it impossible to carry out any research. Criminal charges can be laid for contravention. Penalties can be a jail term up to six months, and/or a fine of up to $5000.
• In addition to research facilities, the act covers supply facilities and dog pounds. The Act regulates the transport and euthanasia of animals. It requires that pounds hold dogs for a minimum of three days prior to release for any purpose. This does not include the day of pick-up, or any day that the pound is closed to the public. Municipalities can lengthen the redemption period. The animal can be held as long as necessary for adoption, but cannot be euthanized if requested by a registered research facility in Ontario.

Local Control of Animal Use:

Prior to ordering animals for research, teaching or testing, investigators must fill out a detailed project proposal. All procedures to be performed on animals must be described in detail. The protocol must state the number and type(s) of animals to be used.

These project proposals are submitted to the institutional Animal Care Committee (ACC) for review. The ACC looks at the ethical aspects of the procedures and the acceptability of the methodologies proposed.

Both the CCAC and the Animals for Research Act require that each institution, where research, teaching or testing involving animals occurs, have an Animal Care Committee. Membership in these ACC's includes scientists experienced in research animal care and use, a veterinarian, a non-animal user, and a community representative. Community members must not be affiliated with the institution. These community members have an important role on the animal care committee: they are the eyes of the general public.

In addition to the review of the protocol by the ACC, all research protocols are peer-reviewed for scientific merit.

Education:

It is important that those working with animals (animal caretakers, investigators, technicians, etc.) know the animal that they are working with. They must know the normal behaviour and health of not only the species they are working with, but the strain. It is important that those performing procedures on animals be well trained. This way, there is less stress for the animal and for the operator, and makes for better research.

How We Care for Our Laboratory Animals:

Housing:

Appropriate animal caging is described in the "CCAC Guide to the Care and Use of Experimental Animals," Volume 1, 2nd Edition. Generally, cages with contact bedding are preferable over stainless steel suspended caging. In the past, stainless steel caging was recommended for hygienic reasons. As increasing importance is now being placed on reducing stress to animals and ensuring the physical and behavioral requirement of animals, the pendulum has swung back to the use of contact bedding.

Animals should be housed in social situations whenever appropriate and possible. Environmental enrichment appropriate to the species should be provided.

Environment:

• Animals are housed according to species.
• Animal facilities are climate controlled. If animal facilities are located in a multi-use building, the animal facility will have a separate air system. Air is usually 100 percent fresh air, with no recirculation. Fifteen to twenty air changes per hour are recommended.
• Generally, each animal room has individual temperature control, to be adjusted to the optimal temperature for the species. Humidity is held around fifty percent.
• Lighting is on timers to control the cycle, and is controlled for intensity.
• Animals are provided with appropriate feed and water
• Animals are checked daily for any signs of ill health or stress.

Criteria for Early Euthanasia:

The criteria for early euthanasia must be clearly defined prior to commencing any work involving animals.

Death is not an acceptable end point. Non-anaesthetized deaths should not occur in research laboratories.

At The University of Western Ontario, we have developed standard operating procedures outlining the criteria for early euthanasia of rodents and other mammals. These criteria include weight loss of fifteen percent or greater; dehydration; piloerection in rodents; depression; and lethargy.

Anesthetics and Analgesics:

Appropriate anesthetics and analgesics must be used to prevent animals from suffering unnecessary pain. In most cases, analgesics do not confound research results. In fact, preventing pain will speed an animal's recovery from surgery and reduce weight loss.

Recognition of Pain or Distress:

Look for alterations in the animal's activity level, gait, behaviour, vocalization, temperament, appetite, water consumption, and appearance. Look for dull eyes, the hair coat standing on end (piloerection). Has the animal lost interest in its surroundings? Are respiration or heart rate increased?

We must be able to recognize pain in our research animals. It is probably safe to assume that if a similar procedure or situation causes pain in humans, it also causes pain in animals.

Summary:

We take very seriously the issue of utilizing animals in research. If we must use animals, we owe it to them to use them and care for them as humanely as possible. Although the general public agrees that it is necessary and acceptable to use animals for medical research, many think that the animals suffer as a result. If the public were educated as to how well we take care of our experimental animals, they would be more comfortable with the process.