The Ethics of Medical and Scientific Research Involving Animals

Written by Dr. David Hanwell

Dr. David Hanwell has worked as a laboratory animal veterinarian in various capacities within the industry, hospital, and academic sectors. He is currently the University of Toronto’s University Veterinarian. In this role, he is responsible for overseeing the ethical animal care and use program at the University, ensuring that appropriate regulatory standards are maintained in research, ranging from biomedical research, basic biology to fieldwork.

Previously, Dr. Hanwell was a clinical veterinarian at the University Health Network (UHN) where he provided clinical and surgical support for research involving a range of species. Prior to joining UHN, he worked at Sanofi Pasteur in its divisions of Research and then Quality Control.

Dr. Hanwell completed both a BSc (University of Guelph) and an MSc (University of Toronto) in Biochemistry, followed by a Doctor of Veterinary Medicine degree at the Ontario Veterinary College. After a stint in private practice, he returned to the University of Guelph where he earned a Doctorate in Veterinary Sciences in Laboratory Animal Science. He is a Diplomate of the American College of Laboratory Animal Medicine, a member of the board of directors of the Canadian Council on Animal Care and has several publications relating to animal use in science.

Introduction

The aim of this article is to provide an overview of how animal research is conducted ethically and humanely in Canada today. As was true when Banting and Best tested insulin in dogs and rabbits in the 1920s, animals are still used in science today to answer questions relating to how the body normally works and what happens in disease states (including ongoing research on diabetes). Given the similarities between humans and some other species, the discoveries made by using animals provides benefits to both people and other animals (e.g. dogs naturally develop diabetes, too).

In addition to the discovery of the role of insulin in helping maintain normal glucose levels in people, animal models have long been used to make other discoveries that have advanced human medicine. Regardless of the scientific purpose, animals are living, feeling beings of importance, so ethical consideration is to be given as to how and when they are used. Medical ethicists refer to the ‘3Rs’ (conceptualized in 1959, well after the discovery of insulin), which is a globally recognized framework that can be seen as the first step to take before using animals in science.

The 3Rs: Replacement, Reduction, Refinement

The 3Rs refer to replacement, reduction, and refinement of animal use in science. Consideration of the 3Rs helps ensure that the animals are only used when needed, in the fewest number possible under conditions that promote good animal welfare and wellbeing throughout their life in science.

Replacement
Only use animals when alternatives, such as computer simulations or tissue cultures, are not available or suitable.
Reduction

Use only the number of animals required to confidently answer the scientific question (i.e., it is possible to use too many and too few animals)
Refinement
- Implement measures that lessen or avoid any negative impact on animal welfare and that promote positive welfare

Oversight of animal use in science

Regulations and standards governing the use of animals in science were established in the 1950s and 60s, around the same time when the conceptualization of the 3Rs entered public discourse. Prior to that, scientists (including Banting and Best) used animals in the way that they believed was most appropriate at the time.

In Canada, there is now a federal oversight body in charge of standards for animal use in science. The Canadian Council on Animal Care (CCAC) is the national peer-reviewed organization responsible for setting, maintaining, and overseeing the implementation of high standards for ethical animal care and use in science throughout Canada. For an institution to receive federal grant funds for research, CCAC accreditation is required if animal work is performed (I.e., it must have a Good Animal Practice certificate). More on the certification process can be found here. Additionally, in Ontario, there are laws that regulate animal use in research (I.e. Animal for Research Act). The Act requires that Inspectors perform unannounced visits to encourage legal requirements to be always met.

Oversight body officials regularly visit institutions to check for compliance with standards and requirements. These visits serve to evaluate many aspects of the program (highlighted below). Any identified issues must be addressed for animal use in science to continue at the institution. Information on other Canadian laws and policies surrounding animal care and use in science can be found here.

In addition to ‘external’ oversight by regulators, institutions are required to have ‘internal’ oversight procedures for animal use activities on a day-to-day basis. This ongoing scrutiny is to ensure that research institutions’ Ethical Animal Care and Use Programs meet all applicable standards. To make sure this process is in place, the institution designates a Senior Administrator with overall responsibility for the program, and the administrator, in turn, delegates an Animal Care Committee to carry out day-to-day oversight.

Animal Care Committee (ACC) – The institutional ACC is responsible for ensuring that all aspects of its Ethical Animal Care and Use program meet standards and requirements.

The ACC must have a varied membership that includes many different perspectives:
- Experienced veterinarian(s);
- Member(s) of the community (representing the public);
- Scientists/teachers experienced in working with animals;
- Technicians experienced in supporting animal care;
- Student representative (where students are present);
- Other members with relevant knowledge (e.g. in health and safety requirements, biostatistics/study design).

Ethical Animal Care and Use Program

Animal care and use programs have many components:

Animal Care Committees (described above)

Before any scientific activity can begin, ACCs must review and approve the plan (or ‘protocol’) for animal use to ensure that each of the 3Rs have been adequately considered.

Post-approval monitoring visits

Once the ACC approves the protocol, announced and unannounced visits are made to areas where animals are housed by ACC delegates to ensure that the mandated practices and procedures are being performed.

Source and type of animals

Institutions should use ethical sources of animals, such as commercial suppliers, which produce animals for the purpose of scientific use.

The species must be deemed appropriate for the study of the area of science under investigation (e.g. to model diabetes)

“Dogs were the preferred animal model in the initial studies on diabetes because of their availability, the fact that their anatomy was well understood, hence making surgical techniques more efficient and most importantly, because at the time they began their experiments a large volume of blood needed to be sampled, thus the research animal could not be any smaller. While in the course of their work, with newer methods being developed to test blood sugar levels in smaller volumes of blood, the team switched to smaller animals (rabbits). In fact, they acknowledge that the development of such techniques allowed their work to be done more precisely and more quickly.” (Reference)

A range of species is used in diabetes research today and largely involve various rodent models. Each animal model varies in how it relates to human physiology. Model choice is influenced by other factors as well.

Housing/environment:

Enclosures where animals are housed must be appropriate in size and design. Food, water, and bedding is to be provided and changed at appropriate frequencies (e.g. diabetic animals may urinate more often than normal animals). Environmental conditions are to be maintained to keep the animals comfortable (e.g. air quality, lighting, noise). They should also be able to perform normal behaviours and activities (e.g. climbing, chewing, housed with other animals to allow socialization and play).

Training/competency

An ethical care program includes training in the necessary knowledge and skills required to perform procedures in a way that minimizes negative impacts on the animals (e.g. surgical skills to remove an animal pancreas to induce diabetes, as Banting and Best did). Only researchers who demonstrate competence can perform procedures on animals.

Scientific procedure spaces and equipment

Procedure and surgical spaces are to be clean, tidy, and activity appropriate (e.g. like exam and surgery rooms used in human medicine). Procedures are to be performed according to modern, ACC-approved standards. To secure approval, researchers provide details to the ACC, outlining what will be done to the animals, including the frequency and duration of procedures (e.g. fasting animals prior to assessing their ability to maintain proper blood glucose levels). A description of when the scientific objectives will be considered achieved and the study complete must also be included.

If a procedure is new, ‘pilot studies’ may be initially performed on non-animal objects and/or small numbers of animals at first to refine the technique (e.g. testing a new insulin product or administration device)

Vet care and support

Veterinarians and veterinary technicians play important roles in ensuring ethical animal care and use. These professionals ensure that animal welfare is maintained at an appropriate level by overseeing the maintenance of proper standards. They identify and address the husbandry and care needs of the animals, particularly if their health is impacted (e.g. by inducing diabetes). They also contribute to the refinement of procedures and practices relating to animal care and use.

Humane interventions

If or when animals are expected to be negatively impacted (e.g. due to advanced diabetes), researchers must plan appropriate interventions, monitor animals and take steps when necessary to alleviate the condition (e.g. providing fluids for dehydration due to advanced diabetic state). The ACC requires that such interventions are established prior to the commencement of any scientific activity and then refined as necessary based on the experience gained from the study and from the work of others in the field (I.e. best practices that relate to advancement of the 3Rs are to be published and shared).

Final disposition

Once the study ends, animals may be adopted out or (most commonly) humanely euthanized (e.g. to examine many tissues for the microscopic and molecular effects of a new diabetes treatment to see if it is safe and effective for human use). If humane euthanasia is performed, it must be conducted according to CCAC standards. The method used must be approved by the ACC and only carried out by trained and competent personnel.

Summary

Research into how diabetes can be better treated and prevented, in both people and animals, is ongoing. Some diabetes research can be conducted without animals. However, animals cannot yet be replaced completely in the experimental process. When animals are still required, researchers must apply the 3Rs to ensure ethical care and use. Oversight of all aspects of animal care and use is provided at multiple levels, including via regulatory bodies, ACCs and veterinary staff. Many animal models exist that enable diabetes to be better understood, resulting in new therapies and devices that help both people and animals.

Teaching Resources

For teachers or students interested in learning more about animal ethics and regulation, these links may serve useful to begin your investigations.