RESEARCH ANIMALS
Overview || Current Research || Past Research
OVERVIEW
The total number of animals used globally in research each year is currently unknown, but it is likely to be in the hundreds of millions. Canada alone uses approximately 2 million animals in research each year, the majority of which are mice and rats. These animals are used for a variety of purposes, including fundamental research, medical studies, product development, regulatory testing of products, and education and training. At the UBC Animal Welfare Program, we have been investigating a number of welfare issues relating to research animals. Our approaches range from research into reducing pain and distress resulting from laboratory procedures, improving the laboratory environments of research animals, exploring how recent developments in research challenge our ability to protect welfare, to understanding attitudes of people towards animal use.
The Animal Welfare Program's research on laboratory animals is led by faculty members:
The Program works with UBC veterinarians and Dr. Gilly Griffin (Guidelines Program Director at the Canadian Council on Animal Care) in its research.
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CURRENT RESEARCH
Humane Euthanasia of Laboratory Rats and Mice
Animal Welfare in Genomic Research: A Bibliometric Analysis of Changing Patterns in Animal Use
Humane Euthanasia of Laboratory Rats and Mice
Currently, the most common method of euthanasia for laboratory rodents is exposure to carbon dioxide. However, increasing evidence - including that provided by AWP alumnus Lee Niel, see below - suggests that this method causes both pain and distress to rodents. The AWP is interested in finding a humane alternative to carbon dioxide euthanasia. We have tested rodent aversion to several other agents, including argon and the inhalant anaesthetics isoflurane and halothane. Argon is an inert gas and therefore it is tasteless, odourless, and safe. Although this gas causes little to no aversion in humans and birds, we have shown that it does cause aversion in laboratory rodents. Inhalant anaesthetics are commonly used to induce unconsciousness in laboratory rodents undergoing surgery, and we found that it causes the least aversion.
To test rodent aversion to these agents, we use approach-avoidance testing. In this type of testing, animals are simultaneously exposed to a positive stimulus and a negative stimulus, and must choose whether they are willing to tolerate the negative stimulus in order to access the positive stimulus. Specifically, rodents are trained to enter a compartment that contains Cheerios; once they start eating, a gas is turned on and the animals must choose whether they find the gas aversive enough to warrant abandoning their Cheerios. The goal is to find an agent that the animals do not mind - this will be apparent if they decide to remain in the compartment to eat their treat. If the animals decide to remain in the compartment until they lose consciousness, they are promptly removed from the compartment and allowed to recover. All the animals we use are surplus animals; we do not euthanize any animals during the course of these experiments.
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Assessing people’s attitudes towards animal use and genetic modification using a web-based interactive survey
Worldwide Trends in the Use of Animals in Research
The Contribution of Genetically Modified Animal Models The 3Rs – Reduction, Replacement and Refinement – first proposed in 1959, have become widely accepted principles in the governance of humane animal research. However, there is substantial variation in the ways different countries document numbers and types of research animals used, making it difficult to determine how well the 3Rs are being implemented. Here we provide the first data illustrating worldwide trends in research animal use. To document global trends in animal use we sampled 2961 articles from 24 countries, published between 1983 and 2007 in 4 scientific journals. We show that the percentage of articles reporting animal use has risen in the past 15 years. The rising popularity of genetic modification methods contributes to this trend: reported genetically modified animal use has more than doubled since 1997. We also show that mice are most commonly used for genetic modification, and that even in 2007, relatively inefficient random integration methods were still widely used to achieve genetic modification. These results illustrate shortcomings in efforts to implement the 3Rs in animal research.
An Interactive Web-based Survey to Assess How People’s Willingness to Support the Use of Animals in Research is Affected by the Regulatory System
Accurate information about current concerns of members of the public are important in considering whether or not policies on research involving animals are likely to be supported by the majority of the population. However, because of methodological constraints, opinion polls are often of limited use. Many surveys use abstract terminology relating to biotechnology, which is likely to produce responses with only a limited degree of validity because of the public’s lack of familiarity with this terminology. In addition, surveys typically do not provide insight into reasons underlying responses to particular questions (Heijs, Midden,& Drabbe, 1993).
The proposed project will use an interactive web-based survey to examine how the willingness of the public to support the use of animals in research is affected by the regulatory oversight system. The web-based survey will be developed in collaboration with the NERD team at the UBC Centre for Applied Ethics. The style of the survey will follow a previously successful template, with appropriate adjustments for the questions being asked. The template allows participants to leave comments about why they gave the answers they did, and in doing so provides rich detail on how people make decisions.
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Animal Welfare in Genomic Research: A Bibliometric Analysis of Changing Patterns in Animal Use
In recent years there has been an increasing number of animals used in research, primarily as a result of an increase in the use of genetically modified (GM) animals. Unfortunately there is a paucity of information on how genomic research affects animal welfare. The ethical justification for use of animals in research is traditionally based on harm-benefit evaluations. However, our modest understanding of the nature and extent of harm to GM animals makes such assessments imprecise. To address this gap, this study is using published research to develop a more detailed understanding of welfare impacts that result from use of animals in genomic research.
Using bibliometric-style methods we are:
- collecting data on both GM and non-GM animals;
- describing numbers, species and strains of GM animals used;
- describing the genomic techniques and procedures;
- characterizing types of welfare concerns that arise.
Our ultimate goal is to sample original research articles from 9 different journals selected on the basis of their topical nature and impact factor. We are collecting data from 1980-2006, which reflects the birth and continuing activity of genomics. Articles from 300 issues (2 issues per year, each with around 10-12 original research articles) are being sampled. Wherever research publications are lacking in welfare information, we will utilize other published sources, such as documents from commercial animal suppliers. Preliminary results show that 53.3% of all articles involved non-human vertebrates (nhvs) (n=120). Of those articles containing nhvs, 32.8% involved GM animals. Of this research, 90.4% used GM mice, 4.8% used GM pigs and the remaining research involved frogs and zebrafish. The most frequently used GM models were ‘knock-outs’ created by embryonic stem cell techniques (52.4% of GM studies). Based on data from many institutes worldwide, this study will put information about GM animal numbers and resulting welfare concerns into a larger perspective. This may help us examine whether current policies sufficiently address these welfare concerns and as a result enable us to recommend ways in which genomic procedures may be refined to improve animal welfare.
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PAST RESEARCH
The Three Rs in the pharmaceutical industry: perspectives of scientists and regulators
The Role of the Animal Ethics Committee in Achieving Humane Animal Experimentation
Improved environments for laboratory rats
Assessment of Rodent Euthanasia Procedures
The Three Rs in the pharmaceutical industry: perspectives of scientists and regulators
– Nicole Fenwick (M.Sc.)
Six drug regulatory reviewers and 11 pharmaceutical industry scientists were interviewed to explore their perspectives on obstacles and opportunities for greater implementation of the Three Rs (replacement, reduction, refinement) in drug research and development.
Participants generally supported the current level of animal use in the pharmaceutical industry and viewed in vitro methods as supporting, but not replacing, the use of animals. Obstacles to greater use of the Three Rs cited by participants included the lack of non-animal alternatives; requirements for statistical validity; reluctance by industry and regulators to depart from established patterns of animal use; the priority of commercial objectives ahead of the Three Rs; and concern that less animal testing could jeopardize human safety. Opportunities identified for the Three Rs included: the development of better animal models including genetically modified (GM) animals; pursuit of more basic knowledge, notably drug action on gene expression; re-use of animals; greater use of pilot studies; using enough animals per test to avoid repeating inconclusive studies; regular review of animal data in regulatory requirements; and following the regulatory option of combining segments of reproductive toxicology studies into one study.
In some areas, greater implementation of the Three Rs seemed well aligned with industry priorities, for example, phenotypic characterization of GM animals and validation of alternative methods. In other areas, wider use of the Three Rs may require building consensus on areas of disagreement including the usefulness of death as an endpoint, the suitability of re-using animals, and whether GM animals and the use of pilot studies contribute to reduction.
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The Role of the Animal Ethics Committee in Achieving Humane Animal Experimentation
– Catherine Schuppli (Ph.D.)
Institutional Animal Ethics Committees (AECs) are the principal means of ensuring the ethical use of animals in research in many countries, yet we understand very little about how they function and how effective they are in implementing policy and achieving their stated aims. To answer these questions, an ethnographic study involving participant observation and in-depth interviews with 28 members of four university AECs in western Canada was carried out. The major focus of protocol review by committee members was reducing harm to animals, with limited focus on the ethical justification of research despite this being stressed in policy as a goal of AEC’s. In part, this may be due to confusion over the relation between AEC review and scientific peer review by granting agencies, with some members believing that ethical justification is decided by scientific peer review. Members were also unclear on the distinction between the different elements that go into decisions about ethical justification. Use of cost-benefit assessment, although prescribed by policy, did not cover the various other decision-making approaches that members described using (e.g. moral intuition). Comments by members identified several factors that could hinder application of the Three Rs (Replacement, Reduction, Refinement); these include an incomplete understanding of the concepts, different interpretations of harm, and different beliefs about the moral significance of pain and suffering. Moreover, some ethical issues do not lend themselves to the utilitarian thinking underlying the Three Rs. Independence of the AEC from the institution (as required by policy) may not be realized because of the predominance of institutional scientists on AECs, recruitment of affiliated community members, and the potentially intimidating atmosphere for community members. Also, policy is unclear about the role of the community member. AEC effectiveness could be improved by clarifying the role of the community member, the relation between AEC and scientific peer review, and the elements of cost-benefit assessments, by expanding policy to acknowledge the various issues and approaches used in decision-making, identifying standards for assessing AEC performance, and expanding the Three Rs to respond to the range of views and values that enter into decisions by AEC members.
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Improved environments for laboratory rats
– Emily Patterson-Kane (Post-doctorate researcher)
Researchers have been using observations of rat behaviour and preference to determine how to select and improve features of laboratory cages. Animal caretakers are often very eager to provide their charges with the most natural and enjoyable environment possible within the confines of the laboratory. To this end, factors such as cage size, social contact, bedding type, and environmental enrichments have been studied in order to design the ideal rat cage. Investigations regarding how foraging theory can be used to measure the value that rats place on different items such as social contact and the presence of cage fixtures. This information is intended to inform animal caretakers about the most effective improvements they can make to the conditions of their animals.
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Assessment of Rodent Euthanasia Procedures
– Lee Niel (PhD)
In Canada alone, approximately 1,000,000 mice and rats are used for research each year, and many more are required for breeding of experimental stock. Of all laboratory procedures, euthanasia is the most common one, as virtually all animals are euthanized to alleviate pain, to collect tissues, or to reduce surplus stock. Regulations and guidelines in Canada, the United States and the European Union state that euthanasia must be relatively quick and painless. Current methods of euthanizing small rodents include physical techniques such as cervical dislocation or decapitation, chemical agents such as injectable anesthetics and exposure to volatile anesthetics and other gases. The method that is chosen is dependent on the number of animals to be killed, the research purpose and the equipment that is available. The advantage of inhalant anesthetics and gases is that they involve minimal handling and restraint and minimal chance of operator error.
One of the most common methods of euthanasia for small laboratory rodents is exposure to carbon dioxide (CO2) gas. Animals are either placed in a chamber that has been pre-filled with the gas or one where the gas concentration gradually increases, causing unconsciousness followed by death. Carbon dioxide is popular because it is easy to deliver with little chance of error, it involves minimal handling and restraint distress for the animal, it is relatively inexpensive and requires minimal equipment, and it is safe for laboratory workers.
Although CO2 has many advantages, there is ongoing debate as to whether it causes pain and distress in rodents such as rats and mice. In our research at UBC, researchers have been trying to determine whether CO2 could be used to humanely euthanize rats. Animals used in this research were surplus and were already slated for euthanasia by the university. Approach-avoidance testing was used to see whether rats were willing to stay in a chamber where the concentration of CO2 gas was gradually increasing in order to consume a reward of 20 Cheerios™, or whether they found the gas aversive enough to forgo the reward and leave the chamber. Results show that rats always left the chamber before loss of consciousness, even after being food deprived for up to 24 hours. This aversion to CO2 was not caused by pain or by fear of novelty, but was most likely due to dyspnea (a sensation of breathlessness). Similar to other studies, researchers at UBC have concluded that CO2 euthanasia is aversive and therefore, alternative methods are needed.
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