Institutional and IACUC responsibilities for animal care and use education and training programs

Training and instruction of personnel are important components of animal care and use programs because they help to ensure the health and welfare of the animals and the integrity of the research or testing results. Training also helps to promote the consideration of alternatives, recognition of animal pain and distress, appropriate use of pain-relieving agents, aseptic technique, pre- and post-procedural care, and personnel health and safety. While individuals who provide the care for or conduct research or testing in laboratory animals should take personal responsibility for ensuring that they have the skills to perform their duties, the institution is ultimately responsible for ensuring their competency. The institution is also responsible for providing the training or instruction that is required by federal legislation, regulations, and policies. The institutional animal care and use committee (IACUC) is responsible for ensuring, as part of their review of research activities, that the personnel are capable of performing the procedures described. The IACUC must also assess the institution's training program as part of their semiannual animal care and use program review and make recommendations regarding training to the institutional official. This article provides a comprehensive overview of the US regulatory mandates for training and personnel qualification.     

Training for reduction in laboratory animal use

Reduction, refinement and replacement of laboratory animals wherever possible, are the guiding principles of the Federation of European Laboratory Animal Science Associations (FELASA) education guidelines. Of these, reduction is probably the least understood. Reduction and refinement are dependent upon each other. In the reduction "axis", there is a window of appropriate numbers of animals; too few and the experiment will lack power--too many and animals will be wasted. Reduction must be understood as the appropriate number of animals required for each experiment. The refinement "axis" is more straightforward. Better welfare is always desirable. Any factor can interfere with a study in two ways. If it changes the mean, this may not be serious, because it should do so in all groups. If it causes a change in variation, then this is far more troublesome, because this is bound to alter the appropriate number of animals for an experiment. Scientists are definitely concerned about the variation of the characters that they are working with. It is obvious that changes in variation may be study-specific, which makes the formulation of overall guidelines difficult. Indeed, instead of trying to assess the impact of housing and procedures on every possible character, it could be more productive to look at the effects of welfare indicators on variation, with the understanding that low variation here is likely to be reflected by low variation in most other characters, while aiming to achieve the most uniform welfare of the animals in the study.     

Physiologically-based pharmacokinetic modelling for the reduction of animal use in the discovery of novel pharmaceuticals

The challenges of physiologically-based pharmacokinetic (PBPK) modelling and approaches to replacing the use of animals, in order to determine drug pharmacokinetics, are discussed. Reference is made to the limitations of in vivo animal studies in drug discovery. In particular, the ways in which animal studies contribute to drug attrition during the post-preclinical phase of testing are considered.     

Considerations in the development of live biotherapeutic products for clinical use

Food products in the United States (U.S.), including dietary supplements, may contain live microorganisms and can be promoted for general health, nutritional, or structure/function claims. In contrast, such preparations used with the intention of having a preventive or therapeutic effect in humans are regulated by the Food and Drug Administration (FDA) in the U.S. as biological products, specifically as live biotherapeutic products (LBPs). Discussion of considerations in the early development of LBPs may aid in preparation of an Investigational New Drug Application (IND) that is designed to collect clinical data to support marketing approval of a LBP in the U.S. for a specific clinical use. Product information is an important component of an IND to support a proposed clinical study.     

Seaweeds for animal production use

Early scientific studies conducted at the turn of the twentieth century failed to support the inclusion of seaweeds into animal rations at high inclusion rates. At that time, based on proximate analysis and energy availability studies, dried seaweeds or kelp meal largely fell out of favor as a recommended animal feed source. Nevertheless, kelp meal was still regarded by some as having properties which improved animal health and productivity which were not conveniently explained by conventional feed analysis. In the 1970s, research leads to the discovery that chelated micromineral sources were more efficient for the delivery of microelements than conventional inorganic sources. This prompted renewed interest in seaweeds as rich sources of over 60+ microelements. However, it was only in the early 2000s, when detailed analysis of the complex structure of the polysaccharides associated with seaweeds was tied to their prebiotic actions, that a clear explanation for the basis of productivity and health enhancement was attained. Further analysis indicated that other constituents in various brown seaweeds such as phlorotannins and antioxidants also contributed to the observed bioactivities. Of all of the brown seaweeds cited in studies, the one most scientifically documented is Ascophyllum nodosum, and of all of these sources, Tasco®, a sundried, high-quality macroalgal product, produced by Acadian Seaplants has been the most studied. The latest studies of Tasco® suggest prebiotic potencies at least five times that of the reference prebiotic inulin with additional performance-enhancing benefits in animal rations that rival antibiotic inclusions.     

Special welfare concerns in countries dependent on live animal trade: the real foreign animal disease emergency for Canada

Any outbreak of an Office International des Epizooties trade-disrupting (previously List-A) disease, such as classical swine fever or foot and mouth disease in a previously disease-free region can have severe consequences for nonhuman animal welfare. In addition to animals destroyed for the purposes of disease eradication, certain preexisting trade patterns may result in welfare slaughter programs affecting many more animals than the disease eradication effort. Welfare slaughter is the destruction of healthy animals to prevent overcrowding on farms under movement restriction and as a consequence of loss of access to live animal export markets. Governments of European countries have anticipated welfare slaughter as part of their disease eradication preparedness. The concept of welfare slaughter and the resource implications thereof have not been included in current, published, livestock disease emergency-planning documents in Canada or the United States. Animal welfare, specifically the killing of healthy animals (not foreign animal disease eradication) has been the focus of public concern in recent disease-eradication efforts in Europe. North American organizations responsible for livestock exotic disease emergency preparedness need to expand their plans to include welfare slaughter.     

A stomach sampler for use on live fish

A stomach sampler for live fish is described and its construction outlined; 50 adult perch were sampled, subsequently killed and dissected to assess the efficiency of the device. Survival of previously sampled fish was followed using individually recognisable dorsal fin tags.     

Strategies for avoiding reinventing the precollege education and outreach wheel

The National Science Foundation's recent mandate that all Principal Investigators address the broader impacts of their research has prompted an unprecedented number of scientists to seek opportunities to participate in precollege education and outreach. To help interested geneticists avoid duplicating efforts and make use of existing resources, we examined several precollege genetics, genomics, and biotechnology education efforts and noted the elements that contributed to their success, indicated by program expansion, participant satisfaction, or participant learning. Identifying a specific audience and their needs and resources, involving K-12 teachers in program development, and evaluating program efforts are integral to program success. We highlighted a few innovative programs to illustrate these findings. Challenges that may compromise further development and dissemination of these programs include absence of reward systems for participation in outreach as well as lack of training for scientists doing outreach. Several programs and institutions are tackling these issues in ways that will help sustain outreach efforts while allowing them to be modified to meet the changing needs of their participants, including scientists, teachers, and students. Most importantly, resources and personnel are available to facilitate greater and deeper involvement of scientists in precollege and public education.     

Bioluminescent imaging to monitor tumor progression and metastasis in live animal

Animal models allowing more sensitive and early detection of tumorigenesis and metastasis are instrumental in the fight for developing effective therapies against aggressive forms of cancer. In the present chapter, the advantages and limitations of the bioluminescent imaging (BLI) approach are discussed. Although BLI provides rapid, highly sensitive, noninvasive and quantitative detection of small tumors and micrometastases, several issues like the low anatomic resolution or the attenuation of the luminescent signal with tissue depth must be considered when using this technology.     

The choice of animal model and reduction

Careful choice of the animal model is essential, if research is to be conducted efficiently, by using the minimum number of animals in order to provide the maximum amount of information. Inbred strains of rodents provide an excellent way of controlling and investigating genetic variation in characters of interest and in response to experimental treatments. Outbred stocks, in which genetic and non-genetic factors are inextricably mixed, are much less suitable, because random and uncontrolled genetic variation tends to obscure any treatment responses. In some cases, the use of inbred strains has led to major advances in scientific understanding. The specific example given here is in the understanding of host-parasite relationships but, more generally, inbred strains have been of critical importance in research which has resulted in the award of at least 17 Nobel prizes. And yet, despite the extensive literature on the properties and scientific value of inbred strains, many scientists continue to use outbred stocks in the mistaken belief that the use of such animals will, in some mysterious way, make their research more applicable to humans. There is really no evidence that this is so, and there is much evidence that the use of inbred strains has been highly successful in many disciplines.     

Estimates for worldwide laboratory animal use in 2005

Animal experimentation continues to generate public and political concern worldwide. Relatively few countries collate and publish animal use statistics, yet this is a first and essential step toward public accountability and an informed debate, as well as being important for effective policy-making and regulation. The implementation of the Three Rs (replacement, reduction and refinement of animal experiments) should be expected to result in a decline in animal use, but without regular, accurate statistics, this cannot be monitored. Recent estimates of worldwide annual laboratory animal use are imprecise and unsubstantiated, ranging from 28-100 million. We collated data for 37 countries that publish national statistics, and standardised these against the definitions of 'animals', 'purposes' and 'experiments' used in European Union Directive 86/609/EEC. We developed and applied a statistical model, based on publication rates, for a further 142 countries. This yielded our most conservative estimate of global animal use: 58.3 million animals in 179 countries. However, this figure excludes several uses and forms of animals that are included in the statistics of some countries. With the data available, albeit for only a few countries, we also produced, by extrapolation, a more comprehensive global estimate that includes animals killed for the provision of tissues, animals used to maintain genetically-modified strains, and animals bred for laboratory use but killed as surplus to requirements. For a number of reasons that are explained, this more-comprehensive figure of 115.3 million animals is still likely to be an underestimate.