A self-assessment survey of the Institutional Animal Care and Use Committee, Part 1: animal welfare and protocol compliance

Nearly half of all external grants from the US National Institutes of Health require approval by the recipient organization's Institutional Animal Care and Use Committee (IACUC) before the funds can be used for research with animals. Given that large sums of money are spent annually on research involving animals, studies evaluating the strengths, weaknesses and overall effectiveness of IACUCs and similar animal welfare committees are needed. The authors designed and carried out a self-assessment survey on IACUC function and effectiveness. They found that 98% of all respondents believed that their IACUCs advanced animal welfare, but in many instances, veterinarians' responses to individual survey items were significantly different from those of other IACUC members. Protocol compliance, protocol review training and better understanding among non-committee members of the need for regulatory oversight are some areas where improvements could be made. Less than 50% of respondents stated that literature searches to find alternatives to animal use or painful or distressful procedures were helpful.     

Should IACUCs review scientific merit of animal research projects?

Whether IACUCs should review animal research protocols for scientific merit is not addressed in the federal regulations, resulting in ongoing confusion on the subject. The authors examine this issue, discuss the pros and cons, suggest how IACUCs can go about reviewing protocols for scientific merit, and question what effect recent changes in regulations will have on this issue.     

Ten practical realities for institutional animal care and use committees when evaluating protocols dealing with fish in the field

Institutional Animal Care and Use Committee’s (IACUCs) serve an important role in ensuring that ethical practices are used by researchers working with vertebrate taxa including fish. With a growing number of researchers working on fish in the field and expanding mandates of IACUCs to regulate field work, there is potential for interactions between aquatic biologists and IACUCs to result in unexpected challenges and misunderstandings. Here we raise a number of issues often encountered by researchers and suggest that they should be taken into consideration by IACUCs when dealing with projects that entail the examination of fish in their natural environment or other field settings. We present these perspectives as ten practical realities along with their implications for establishing IACUC protocols. The ten realities are: (1) fish are diverse; (2) scientific collection permit regulations may conflict with IACUC policies; (3) stakeholder credibility and engagement may constrain what is possible; (4) more (sample size) is sometimes better; (5) anesthesia is not always needed or possible; (6) drugs such as analgesics and antibiotics should be prescribed with care; (7) field work is inherently dynamic; (8) wild fish are wild; (9) individuals are different, and (10) fish capture, handling, and retention are often constrained by logistics. These realities do not imply ignorance on the part of IACUCs, but simply different training and experiences that make it difficult for one to understand what happens outside of the lab where fish are captured and not ordered/purchased/reared, where there are engaged stakeholders, and where there is immense diversity (in size, morphology, behaviour, life-history, physiological tolerances) such that development of rigid protocols or extrapolation from one species (or life-stage, sex, size class, etc.) to another is difficult. We recognize that underlying these issues is a need for greater collaboration between IACUC members (including veterinary professionals) and field researchers which would provide more reasoned, rational and useful guidance to improve or maintain the welfare status of fishes used in field research while enabling researchers to pursue fundamental and applied questions related to the biology of fish in the field. As such, we hope that these considerations will be widely shared with the IACUCs of concerned researchers.     

The search for refinement alternatives: when you've just got to use animals

Refinements to animal-use protocols can help reduce animal pain and distress, thus producing cleaner data. Yet, most researchers neglect a refinement search, despite legal mandates, because the information is not readily available. What's more, IACUCs may have difficulty assessing researchers' refinement searches. The author offers some solutions.     

Fish research and the institutional animal care and use committee

Fish represent the most diverse group of animals in the vertebrate phylum. The more than 25,000 species are characterized by an array of anatomical, biochemical, physiological, and behavioral repertoires. For this reason, it is difficult to develop a comprehensive guideline on the care and use of fishes. Institutional animal care and use committees (IACUCs) meet the challenge of ensuring adequate fish welfare using guidelines (Animal Welfare Act [AWA] and Public Health Service [PHS] Policy and their guides) derived mainly from the care and use of mammalian species, which may not be optimal for regulating fish research, teaching, or extension activities. Discussion focuses on various issues that often confront IACUCs in meeting regulatory requirements while assuring proper fish welfare. Issues include questions concerning animal tracking and inventory, utilization of fisheries bycatch, facility inspections in remote locations, and euthanasia. Common sense solutions appropriate for field and laboratory fish activities are suggested, which should help investigators, IACUCs, and regulatory agencies meet PHS and AWA objectives.     

August Weismann's theory of the germ-plasm and the problem of unconceived alternatives

I have argued elsewhere that scientific realism is most significantly challenged neither by traditional arguments from underdetermination of theories by the evidence, nor by the traditional pessimistic induction, but by a rather different historical pattern: our repeated failure to conceive of alternatives to extant scientific theories, even when those alternatives were both (1) well-confirmed by the evidence available at the time and (2) sufficiently scientifically serious as to be later embraced by actual scientific communities. Here I use August Weismann's defense of his influential germ-plasm theory of inheritance to support my claim that this pattern characterizes the history of theoretical scientific investigation generally. Weismann believed that the germ-plasm must become disintegrated into its constituent elements over the course of development, I argue, only because he failed to conceive of any possible alternative mechanism of ontogenetic differentiation. This and other features of the germ-plasm theory, I suggest, reflect a still more fundamental failure to imagine that the germ-plasm might be a productive rather than expendable resource for the cell. Weismann's case provides impressive support for the problem of unconceived alternatives while rendering its challenge to scientific realism deeper and sharper in a number of important ways.     

The Assessment of Science: The Relative Merits of Post-Publication Review,the Impact Factor,and the Number of Citations

The assessment of scientific publications is an integral part of the scientific process. Here we investigate three methods of assessing the merit of a scientific paper: subjective post-publication peer review, the number of citations gained by a paper, and the impact factor of the journal in which the article was published. We investigate these methods using two datasets in which subjective post-publication assessments of scientific publications have been made by experts. We find that there are moderate, but statistically significant, correlations between assessor scores, when two assessors have rated the same paper, and between assessor score and the number of citations a paper accrues. However, we show that assessor score depends strongly on the journal in which the paper is published, and that assessors tend to over-rate papers published in journals with high impact factors. If we control for this bias, we find that the correlation between assessor scores and between assessor score and the number of citations is weak, suggesting that scientists have little ability to judge either the intrinsic merit of a paper or its likely impact. We also show that the number of citations a paper receives is an extremely error-prone measure of scientific merit. Finally, we argue that the impact factor is likely to be a poor measure of merit, since it depends on subjective assessment. We conclude that the three measures of scientific merit considered here are poor; in particular subjective assessments are an error-prone, biased, and expensive method by which to assess merit. We argue that the impact factor may be the most satisfactory of the methods we have considered, since it is a form of pre-publication review. However, we emphasise that it is likely to be a very error-prone measure of merit that is qualitative, not quantitative.

Author summary

Subjective assessments of the merit and likely impact of scientific publications are routinely made by scientists during their own research, and as part of promotion, appointment, and government committees. Using two large datasets in which scientists have made qualitative assessments of scientific merit, we show that scientists are poor at judging scientific merit and the likely impact of a paper, and that their judgment is strongly influenced by the journal in which the paper is published. We also demonstrate that the number of citations a paper accumulates is a poor measure of merit and we argue that although it is likely to be poor, the impact factor, of the journal in which a paper is published, may be the best measure of scientific merit currently available.     

IACUC Challenges in Invertebrate Research

With billions of individuals and possibly hundreds of thousands of genera, invertebrates represent the largest number and greatest diversity of all animals used in research. Although the capacity for nociception is recognized in many invertebrate taxa, researchers and IACUC members are challenged by a lack of clear understanding of invertebrate welfare and by differing standards of moral concern for these taxa. In practice this has led IACUCs to consider invertebrates in two major groups: species worthy of increased moral concern approximating that shown to vertebrate species (this group includes cephalopods and to some extent decapod crustaceans) and all others. This dichotomy has led to differences in how invertebrate research is regulated and documented. This article presents two case studies illustrating specific concerns in invertebrate research protocols and then provides relevant information to address practical IACUC matters related to regulatory and ethical issues, sourcing and record keeping, risk management, assessment of pain and nociception in invertebrates, housing and husbandry, invasive procedures, veterinary care, and humane endpoints.     

Surgical implantation of transmitters into fish

Although the Animal Welfare Act does not cover poikilotherms, individual institutions and policies and legal requirements other than the Animal Welfare Act (e.g., the US Public Health Service and the Interagency Research Animal Committee's Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training) require the review of projects involving fish by institutional animal care and use committees (IACUCs). IACUCs may, however, lack the knowledge and experience to evaluate fish projects judiciously, especially when the projects are in field settings. Surgeries involving implantation of transmitters and other instruments into the coelom, which now comprise a very common research tool in the study of free-ranging fishes, are examples of surgeries that use a broad spectrum of surgical and anesthetic techniques, some of which would not be considered acceptable for similar work on mammals. IACUCs should apply the standards they would expect to be used for surgeries on homeotherms to surgeries on fish. Surgeons should be carefully trained and experienced. Surgical instruments and transmitters should be sterile. Regulations and laws on the use of drugs in animals should be followed, particularly those concerned with anesthetics and antibiotics used on free-ranging fish. Exceptions to surgical procedures should be made only when circumstances are extreme enough to warrant the use of less than optimal procedures.     

Preparation of animals for use in the laboratory: issues and challenges for the Institutional Animal Care and Use Committee (IACUC)

Preparation of animals is important for optimization of animal welfare as well as to minimize interanimal variation, thereby strengthening the quality of data for in vivo studies. These issues are important in the work of institutional animal care and use committees (IACUCs), but they pose many challenges as well. This article provides IACUC members with a resource for use in determining whether and how preparation of animals for research affects the IACUC's responsibilities. The topics addressed are intended to serve as a starting point for consideration and discussion. Questions related to subject selection and acclimation of subjects to experimental housing and procedures are emphasized and should provide IACUC members with a framework for discussion of relevant questions. Guidelines are provided for promoting the acclimation of a number of species to experimental settings. Additional, potentially controversial points are also raised, including the effects on longitudinal data sets of changing subject preparation procedures. The roles of the IACUC in the research endeavor are multifaceted and continuously evolving. As empirical data are produced that affect additional aspects of animal care and use, it is important for these committees to be able to evaluate and, when appropriate, stimulate the implementation of improved procedures and strategies.     

Survey of environmental enhancement programs for laboratory primates

Animal welfare regulations in the United States require that nonhuman primate environmental enhancement plans be made in accordance with currently accepted professional standards; however, little information is available for quantifying common practice. Here we report the results of a 2003 survey that was sent to individuals overseeing enrichment programs at a variety of primate research institutions. The surveys requested information on program administration and management, implementation standards, procedures, and constraints pertaining to major categories of environmental enrichment, as well as intervention plans for animals exhibiting behavioral pathologies. Data were obtained on the management of 35,863 primates in 22 facilities. Behavioral scientists performed program oversight at the majority of facilities. Most programs reported recent changes, most commonly due to external site visits, and least commonly resulting from internal review. Most facilities' institutional animal care and use committees (IACUCs) included of individuals with behavioral expertise, and about two-thirds reported that enrichment issues could influence research protocol design. While most primates were reported to be housed socially (73%), social housing for indoor-housed primates appears to have changed little over the past 10 years. Research protocol issues and social incompatibility were commonly cited constraints. Implementation of feeding, manipulanda, and structural enrichment was relatively unconstrained, and contributions to these aspects of behavioral management generally included individuals in a wide variety of positions within a facility. In contrast, enrichment devices were used on a less widespread basis within facilities, and positive reinforcement programs that involved dedicated trainers were rare. We suggest that altering the role of the IACUC would be a productive avenue for increasing the implementation of social housing, and that an emphasis on prevention rather than intervention against behavioral pathology is warranted. The data from this survey may be useful for anticipating future program evaluations, establishing more effective internal evaluations, and assessing program progress and resource allocation.     

A renewed look at laboratory rodent housing and management

Since its publication in 1996, the Guide for the Care and Use of Laboratory Animals (National Research Council, Washington DC, National Academy Press) has become a primary source of information for institutional animal care and use committees (IACUCs) and research facility managers. In the ensuing years, recommendations relating to laboratory animal care have evolved in response to new scientific information and use of new technology such as ventilated caging. In this article, recent publications are examined to determine the potential impact of new scientific evidence on current practices for the housing and care of laboratory rodents. The discussion points out recent advances in technology and new knowledge of the conditions for the housing of various laboratory rodents, including cage space, single versus group housing, ventilated caging systems, thermoregulation, bedding materials, and enrichment. This new information is provided to aid IACUCs and facility managers in making decisions regarding the housing and care of laboratory rodents.     

Implicit normativity in scientific advice: values in nutrition scientists' decisions to give public advice

This paper focuses on implicit normative considerations underlying scientific advice -- those normative questions, decisions, or issues that scientific advisers and the general public are not fully aware of but that nevertheless have implications for the character of the advice given. Using nutritional science as an example, we identify three such implicit normative issues. The first concerns the aim of scientific advice: whether it is about avoiding harm or promoting good. The second concerns the intended beneficiaries of the advice: whether advice should be framed to benefit the society as a whole or with special concern for the most vulnerable members of the population. The third consideration involves scientific advisers' attempts to balance the strengths of the scientific evidence with the expected consequences of scientific advice. We hope to promote more explicit discussion of these issues among scientific advisers and a wider public.     

RADIATION THERAPY IN BREAST CANCER—A Preliminary Report on the Application of a Technique of the McWhirter Type

A modification of the radiation technique advocated by McWhirter was used in the treatment of 12 patients with carcinoma of the breast. On the basis of observations it is believed that the method has definite merit. It is believed that for patients who have had radical mastectomy, radiotherapy should be protracted over a period of more than three weeks.     

Radiation therapy in breast cancer; a preliminary report on the application of a technique of the McWhirter type

A modification of the radiation technique advocated by McWhirter was used in the treatment of 12 patients with carcinoma of the breast. On the basis of observations it is believed that the method has definite merit. It is believed that for patients who have had radical mastectomy, radiotherapy should be protracted over a period of more than three weeks.     

IACUC issues associated with amphibian research

Numerous species of amphibians are frequently utilized as animal models in biomedical research. Despite their relatively common occurrence as laboratory animals, the regulatory guidelines that institutional animal care and use committees (IACUCs) must employ provide little in the way of written standards for ectothermic animals. Yet, as vertebrates, laboratory amphibians are covered by the National Research Council Guide for the Care and Use of Laboratory Animals and the Public Health Service (PHS) Policy for federally funded research. This article focuses on three issues that are relevant to IACUC oversight of the use of amphibians in research: (1) recommended educational requirements of investigators and animal care staff engaged in research with amphibians, (2) zoonoses and other issues of occupational health importance, and (3) indicators of stress and disease. Addressing these issues should enable investigators, IACUCs, and animal care staff to meet the regulatory expectations of the PHS and accrediting bodies such as the Association for Assessment and Accreditation of Laboratory Animal Care International.     

Pain and distress: what really matters?

Federal regulations mandate the minimization of both pain and distress in laboratory animals. That no clear definition exists for 'distress' complicates its recognition, quantification, and alleviation. The author argues that IACUCs and investigators should shift their focus from pain to distress, and that in doing so both problems will be better dealt with. She discusses criteria for defining 'significant' distress, and offers suggestions for the conduct of studies to determine levels of distress.     

Does the Animal Welfare Act apply to free-ranging animals?

Despite the long-standing role that institutional animal care and use committees (IACUCs) have played in reviewing and approving studies at academic institutions, compliance with the Animal Welfare Act (AWA) is not always complete for government natural resource agencies that use free-ranging animals in research and management studies. Even at universities, IACUCs face uncertainties about what activities are covered and about how to judge proposed research on free-ranging animals. One reason for much of the confusion is the AWA vaguely worded exemption for "field studies." In particular, fish are problematic because of the AWA exclusion of poikilothermic animals. However, most university IACUCs review studies on all animals, and the Interagency Research Animal Committee (IRAC) has published the "IRAC Principles," which extend coverage to all vertebrates used by federal researchers. Despite this extended coverage, many scientists working on wild animals continue to view compliance with the AWA with little enthusiasm. IACUCs, IACUC veterinarians, wildlife veterinarians, and fish and wildlife biologists must learn to work together to comply with the law and to protect the privilege of using free-ranging animals in research.     

Can science justify regulatory decisions about the cultivation of transgenic crops?

Results of scientific studies are sometimes claimed to provide scientific justification for regulatory decisions about the cultivation of certain transgenic crops. A decision may be scientifically justified if objective analysis shows that the decision is more likely than alternatives to lead to the achievement of specific policy objectives. If policy objectives are not defined operationally, as is often the case, scientific justification for decisions is not possible. The search for scientific justification for decisions leads to concentration on reducing scientific uncertainty about the behaviour of transgenic crops instead of reducing uncertainty about the objectives of policies that regulate their use. Focusing on reducing scientific uncertainty at the expense of clarifying policy objectives may have detrimental effects on scientists, science and society.     

Carbon dioxide for euthanasia: concerns regarding pain and distress, with special reference to mice and rats

Carbon dioxide (CO2) is the most commonly used agent for euthanasia of laboratory rodents, used on an estimated tens of millions of laboratory rodents per year worldwide, yet there is a growing body of evidence indicating that exposure to CO2 causes more than momentary pain and distress in these and other animals. We reviewed the available literature on the use of CO2 for euthanasia (as well as anaesthesia) and also informally canvassed laboratory animal personnel for their opinions regarding this topic. Our review addresses key issues such as CO2 flow rate and final concentration, presence of oxygen, and prefilled chambers (the animal is added to the chamber once a predetermined concentration and flow rate have been reached) versus gradual induction (the animal is put into an empty chamber and the gas agent(s) is gradually introduced at a fixed rate). Internationally, animal research standards specify that any procedure that would cause pain or distress in humans should be assumed to do so in non-human animals as well (Public Health Service 1986, US Department of Agriculture 1997, Organization for Economic Cooperation and Development 2000). European Union guidelines, however, specify a certain threshold of pain or distress, such as 'skilled insertion of a hypodermic needle', as the starting point at which regulation of the use of animals in experimental or other scientific procedures begins (Biotechnology Regulatory Atlas n.d.). There is clear evidence in the human literature that CO2 exposure is painful and distressful, while the non-human literature is equivocal. However, the fact that a number of studies do conclude that CO2 causes pain and distress in animals indicates a need for careful reconsideration of its use. Finally, this review offers recommendations for alternatives to the use of CO2 as a euthanasia agent.