Institute For Laboratory Animal Research Research Articles

History of the National Academies of Sciences, Engineering, and Medicine’s Institute for Laboratory Animal Research

The Institute for Laboratory Animal Research (ILAR) was created within the National Academies of Sciences, Engineering, and Medicine (National Academies) in 1953 when biomedical research using animals was in its infancy in terms of quantity, quality, complexity, sophistication, and care. Over the intervening 69years, ILAR has witnessed unprecedented growth, followed by unprecedented decline, and then regrowth in usage of specific species and models and an overall shift in experimental burden away from larger to smaller species (ie, mice, fish, and rats). ILAR has contributed much to the evolution of necessary research using animals and animal models for the benefit of humans, animals, and the environment and to the development and implementation of humane principles and standards for care and use of research animals. ILAR has served as a "neutral broker" seeking consensus, solutions, common ground, and pathways forward for all professional constituencies engaged in conduct of animal research. In 2022, ILAR will become the Board on Animal Health Sciences, Conservation, and Research (BAHSCR) within the Division on Earth and Life Studies of the National Academies and the ILAR Journal will pause publication with volume 62. This manuscript recounts the history and accomplishments of ILAR 1953-2022, emphasizing the past 2 decades. The manuscript draws upon ILAR's communications and previously published histories to document ILAR's leaders, reports, publications, conferences, workshops, and roundtables using text, tables, references, and extensive supplemental tables. The authors' intention is to provide the scientific community with a single source document for ILAR, and they apologize for any omissions and errors.

Сравнительная оценка влияния ресвератрола и карнитина на полнотранскриптомный профиль ткани печени мышей с различной предрасположенностью к развитию алиментарного ожирения

Сравнительная оценка влияния ресвератрола и карнитина на полнотранскриптомный профиль ткани печени мышей с различной предрасположенностью к развитию алиментарного ожирения

Improving animal research reporting standards

For more than 30 years, individuals and organizations have expressed concerns about the quality of reporting the results from and details of research experiments that use animals. These concerns and efforts to establish better standards along with guidelines for researchers (see Sidebar A) have gained more attention and importance lately given the ongoing discussion about a “reproducibility crisis” in biomedical research along with similar efforts to further improve the welfare of laboratory animals. However, implementation of reporting standards by journals and adherence to these by authors is still patchy. Given this variation in awareness and implementation of current reporting standards, the International Council for Laboratory Animal Science (ICLAS) decided to seek to harmonize animal research reporting guidelines so as to encourage improvements in the quality of science where laboratory animals are involved. ICLAS, which was formed under the auspices of UNESCO in 1956 as an international scientific organization to advance human and animal health by promoting the ethical care and use of laboratory animals in research worldwide, believes that improving research reporting will aid the dissemination of responsible research practices worldwide and reduce the impact of cultural factors influencing the ethical use of animals. Here, we present simplified and general reporting principles that would make it easier for both journals and authors to report details of animal experiments. Adoption and implementation of these general principles could improve reproducibility of research results and animal welfare globally. ### Sidebar A: Further reading Papers outlining concerns regarding the reporting of animal experiments Smith JA, Birke L, Sadler D (1997) Reporting animal use in scientific papers. Lab Animal 31: 312–317 Alfaro V (2005) Specification of laboratory animal use in scientific articles: current low detail in the journals’ instructions for authors and some proposals. Methods Find Exp Clin …

Open Science and Reporting Animal Studies: Who's Accountable?

Open Science and Reporting Animal Studies: Who's Accountable?

Bias Detection: Study Identifies Instruments for Evaluating Animal Studies

No good scientist wants to produce, or be accused of producing, a poorly conducted study. Even so, toxicologists conducting animal studies are not widely expected to document the steps they take to ensure internal validity—that is, to prevent their results from being skewed due to a methodological issue (a concept known as risk of bias). This is likely to change soon, and a team of researchers at the University of California, San Francisco (UCSF) has taken a first step toward a solution by conducting a systematic literature review that identifies 30 instruments for evaluating risk of bias in animal research.1 “Risk of bias” refers specifically to the introduction of systematic errors as a result of the way a study was conducted; it is unrelated to prejudice or manipulation of results to achieve a desired outcome. Other aspects of study quality include external validity (the extent to which results can be generalized) and reporting quality (descriptions of the experiment design, conduct, and analysis).2 Tools to assess these other aspects of study quality are familiar to toxicologists,3,4,5 but the concept of risk of bias is relatively new in environmental health, says Kris Thayer, director of the National Toxicology Program’s Office of Health Assessment and Translation (OHAT), who was not involved in the new review. Thayer’s group is leading efforts to incorporate systematic review methodology into OHAT evaluations.6 She says it’s important, when conducting these evaluations, to clearly define which aspects of study quality are being considered and to present them as discrete elements. She lauds the new review for providing a starting point for determining how to evaluate the risk of bias in animal studies. The review presents an inventory of different approaches for assessing existing study-quality tools and summarizes what is known about specific factors as sources of systematic bias. “Although there is a well-developed and empirically based literature on how to evaluate the risk of bias of randomized controlled clinical trials, less is known about how to do this for animal studies,” wrote the team of UCSF researchers, who were led by Lisa Bero, an expert in systematic review methods and evidence-based health care. Bero and her coauthors combed through 45 years of MEDLINE publications and found 3,731 articles describing instruments for assessing risk of bias in animal studies. They identified 30 instruments that assess anywhere from 2 to 25 criteria associated with the risk of bias, methodological, or reporting criteria. Rather than pinpointing a single “best instrument,” the authors attempt to identify the core set of procedures important for evaluating risk of bias in animal studies, Bero says. These procedures include some process of random allocation to experimental groups; a blinded assessment of outcome; statistical tools to be sure that studies aren’t underpowered; recording both inclusion and exclusion criteria to show that the animals were appropriate for the study; and ensuring that all collected data were reported. Figure 1 Bias, or the introduction of errors into experiments, may be one explanation for equivocal research findings. The authors acknowledge that they may not have identified all published assessment instruments because they searched only for English-language publications using just one database. “However,” they wrote, “both our consultation with a librarian and the large pool of studies identified through the electronic search suggests that it was comprehensive.”1 Study coauthor Tracey Woodruff of UCSF’s Department of Obstetrics, Gynecology and Reproductive Sciences and Program on Reproductive Health and the Environment, calls the review “a foundational piece of a broader method that is going to greatly improve our ability to evaluate environmental chemicals.” Woodruff’s group is working to establish how the systematic reviews initially developed for use in the decades-old field of evidence-based medicine can be applied to environmental health and has developed a strategy known as the Navigation Guide.7 Woodruff’s overarching goal is to encourage medical practitioners to educate their patients about hazardous environmental exposures, particularly ones that may affect their reproductive health.8 Malcolm R. Macleod, a professor at the University of Edinburgh’s Centre for Clinical Brain Sciences, who was not involved in the study, calls the review a small but “really important” contribution toward reducing the risk of bias, says. Macleod’s interest in the subject sprang from his work on clinical trials in which drug candidates recommended by animal stroke studies ended up failing in humans. His subsequent analysis9 demonstrated how study quality and publication bias in those animal studies led to a major overstatement of the drugs’ efficacy. His publications and others document that lack of randomization or blinding, failure to specify inclusion/exclusion criteria or use of comorbid animals, and lack of statistical power in animal studies have inflated the estimates of the effects of pharmaceutical interventions for a number of human maladies.10,11,12,13,14 They inspired high-profile pleas to establish better reporting criteria that incorporates risk-of-bias assessments.15,16

Institutional Animal Care and Use Committees: Session Introduction

F or those of us involved with the Department of Defense (DoD), 40 years ago the DoD implemented local com­ mittee oversight and approval responsibilities over re­ search activities. Twenty-five years ago, as you have been reminded, USDA and NIH implemented major revisions to their regulations and policies, respectively, to create what we now know as animal care and use committees. Our three panelists will cover the past, present, and future of the mul­ tiple activities these committees perform to advise and sup­ port the humane and appropriate care and use of laboratory animals. Our first speaker is Dr. Ralph Dell, who is now a private consultant. Previously he served as Director of the Institute for Laboratory Animal Research at the National Research Council and as Chairman of the Institutional Animal Care and Use Committee at Columbia University. Dr. Dell re­ ceived his MD from the University of Pennsylvania and is board certified in Pediatrics. He is a Council member emeri­ tus for AAALAC International. Our next speaker, Dr. Kathryn Bayne, is the Global Director for the Association of Assessment and Accreditation of Laboratory Animal Care International. In this role, she directs the accreditation program worldwide, traveling exten­ sively to advance AAALAC’s accreditation program and laboratory animal welfare. Prior to this position, she worked at the NIH leading a research program on nonhuman primate psychological well-being and environmental enrichment programs for primates, cats, dogs, and swine. She has pub­ lished over 40 articles on the subject, is a certifi ed animal behaviorist, and is internationally renowned for her work in laboratory animal behavior. She has also published exten­ sively on accreditation of laboratory animal programs.

ETHICS AND METHODS FOR BIOLOGICAL RHYTHM RESEARCH ON ANIMALS AND HUMAN BEINGS

This article updates the ethical standards and methods for the conduct of high-quality animal and human biological rhythm research, which should be especially useful for new investigators of the rhythms of life. The editors of Chronobiology International adhere to and endorse the Code of Conduct and Best Practice Guidelines of the Committee On Publication Ethics (COPE), which encourages communication of such updates at regular intervals in the journal. The journal accepts papers representing original work, no part of which was previously submitted for publication elsewhere, except as brief abstracts, as well as in-depth reviews. The majority of research papers published in Chronobiology International entails animal and human investigations. The editors and readers of the journal expect authors of submitted manuscripts to have made an important contribution to the research of biological rhythms and related phenomena using ethical methods/procedures and unbiased, accurate, and honest reporting of findings. Authors of scientific papers are required to declare all potential conflicts of interest. The journal and its editors endorse compliance of investigators to the Guide for the Care and Use of Laboratory Animals of the Institute for Laboratory Animal Research of the National Research Council, relating to the conduct of ethical research on laboratory and other animals, and the principles of the Declaration of Helsinki of the World Medical Association, relating to the conduct of ethical research on human beings. The peer review of manuscripts by Chronobiology International thus includes judgment as to whether or not the protocols and methods conform to ethical standards. Authors are expected to show mastery of the basic methods and procedures of biological rhythm research and proper statistical assessment of data, including the appropriate application of time series data analyses, as briefly reviewed in this article. The journal editors strive to consistently achieve high standards for the research of original and review papers reported in Chronobiology International, and current examples of expectations are presented herein. (Author correspondence: prf@unife.it)

The Institute for Laboratory Animal Research — An International Resource for Promoting the Three Rs

In 1995, an international group of scientists met in Sheringham, Norfolk, UK, for a workshop entitled The Three Rs: The Way Forward. There, with the participation of William Russell and Rex Burch, the group discussed each of the Three Rs in detail, and made specific recommendations on how to promote them within the scientific community. The Institute for Laboratory Animal Research (ILAR) was established as part of the US National Academy of Sciences, to develop and disseminate information and guidelines for the care and use of laboratory animals. Over the years, the focus of ILAR has been to improve the health, welfare, and psychological well-being of the research animal, using the Three Rs as a foundation. ILAR's programmes include an international component, through which it reaches out to other countries via translations of its report; the ILAR Journal, a quarterly publication that focuses on animal models, animal welfare and protocol review; communications and outreach through the ILAR website and presence at scientific meetings; and special reports in which expert committees make recommendations to improve science and animal welfare. Through the efforts of ILAR and similar organisations, it is now recognised that high standards of humane care lead to better science. However, continued effort is needed to promote the Three Rs in developing countries.

International Journal of Sports Medicine – Ethical Standards in Sport and Exercise Science Research

For research that involves human participants or animals to be published in the International Journal of Sports Medicine (IJSM), it must have been conducted in accordance with recognised ethical standards and national/international laws. Authors are required to confirm that these standards and laws have been adhered to by formally citing this editorial within the methods section of their own manuscript. In this editorial, we synthesise the standards and laws into one source for convenience to authors of IJSM submissions. We outline the principles of the World Medical Association Declaration of Helsinki [1] and the Institute for Laboratory Animal Research of the National Research Council's Guide for the Care and Use of Laboratory Animals [2]. We highlight ethical issues included in national/international law and provide guidance on ethical issues common to Sport and Exercise Science.

Adequate Veterinary Care for Animals in Research: A Comparison of Guidelines from Around the World

Many countries, professional organizations, and nongovernmental organizations have issued guidelines for adequate veterinary medical care for laboratory animals. They are thus considered internationally to be an essential component of animal care and use programs. In the United States, the Guide for the Care and Use of Laboratory Animals (the Guide; NRC 1996), a publication of the National Research Council through the Institute for Laboratory Animal Research (ILAR), provides guidelines that serve as the basis for the US Public Health Service Policy on Humane Care and Use of Laboratory Animals. Among the critical topics included in the Guide is veterinary medical care for laboratory animals, and the report’s recommendations outline key fundamental issues for institutions. While the Guide primarily provides guidelines for use in

International Outcry Follows Attacks on Neuroscientist's Home

International Outcry Follows Attacks on Neuroscientist's Home

Ethical and Methodological Standards for Laboratory and Medical Biological Rhythm Research

The main objectives of this article are to update the ethical standards for the conduct of human and animal biological rhythm research and recommend essential elements for quality chronobiological research information, which should be especially useful for new investigators of the rhythms of life. A secondary objective is to provide for those with an interest in the results of chronobiology investigations, but who might be unfamiliar with the field, an introduction to the basic methods and standards of biological rhythm research and time series data analysis. The journal and its editors endorse compliance of all investigators to the principles of the Declaration of Helsinki of the World Medical Association, which relate to the conduct of ethical research on human beings, and the Guide for the Care and Use of Laboratory Animals of the Institute for Laboratory Animal Research of the National Research Council, which relate to the conduct of ethical research on laboratory and other animals. The editors and the readers of the journal expect the authors of submitted manuscripts to have adhered to the ethical standards dictated by local, national, and international laws and regulations in the conduct of investigations and to be unbiased and accurate in reporting never‐before‐published research findings. Authors of scientific papers are required to disclose all potential conflicts of interest, particularly when the research is funded in part or in full by the medical and pharmaceutical industry, when the authors are stock‐holders of the company that manufactures or markets the products under study, or when the authors are a recent or current paid consultant to the involved company. It is the responsibility of the authors of submitted manuscripts to clearly present sufficient detail about the synchronizer schedule of the studied subjects (i.e., the sleep‐wake schedule, ambient light‐dark cycle, intensity and spectrum of ambient light exposure, seasons when the research was conducted, shift schedule in studies involving shift work, and menstrual cycle stage in studies involving young women). Rhythm analysis of time series data should be performed with the perspective that rhythms of different periods might be superimposed upon the observed temporal pattern of interest. A variety of different and complementary statistical procedures can be used for rhythm detection. Fitting a mathematical model to the time series data provides a better and more objective analysis of time series data than simple data inspection and narrative description, and if rhythmicity is documented by objective methods, its characterization is required by relevant parameters such as the rhythm's period (tau), MESOR (time series average), amplitude (range of temporal variation), acrophase (time of peak value), and bathyphase (time of trough value). However, the assumptions underlying the time series modeling must be satisfied and applicable in each case, especially the assumption of sinusoidality in the case of cosinor analaysis, before it can be accepted as appropriate. An important aspect of the peer review of manuscripts submitted to Chronobiology International entails judgment of the conformity of research protocols and methods to the standards described in this article.

Guidelines for the Human Transportation of Research Animals

Transportation of research animals is a major component of the research enterprise but one that can have a substantial negative impact on animal well-being. Both environmental conditions and the novelty of the transportation experience can cause stress, which can result in short-term changes in the physiological and psychological condition of the animals and thus affect subsequent research outcomes, especially if the animals are utilized immediately after transportation. Therefore, the primary goal for all individuals involved in animal transport should be to move them in a manner that does not jeopardize their well-being and ensures their safe arrival at their destination in good health and with minimal distress. While shipments from breeders to research institutions are generally well executed through the use of company-owned fleets of environmentally controlled vehicles, arranging humane transport from vendors without established transport systems, or between research institutions, can be challenging for research facility staff without extensive experience. International transport of nonhuman primates (hereafter primates) is particularly challenging because their shipment and quarantine require adherence to the legislation of each country involved and because few airlines are willing to carry them. What is needed to meet these challenges is comprehensive guidance detailing the potential negative effects of the transportation process on research animal well-being and the steps necessary to minimize adverse effects for the main species transported, as well as the relevant local, national and international regulations and the various organizations involved. Although a working group of the United Kingdom’s Laboratory Animal Science Association (LASA) has recently considered these issues and developed guidance for Europe (Swallow et al. 2005), no single source of such information existed for the United States of America (USA) until publication of this book from the National Research Council’s Institute for Laboratory Animal Research (ILAR).

New Frontiers in Education and Training for the Laboratory Animal Community and the Public: An Overview of Select Proceedings from the June 2006 Forum of the American College of Laboratory Animal Medicine

The proper and humane care and use of laboratory animals and the quality of research results derived from those animals all depend on the personnel who support and work with them. The old adage, “knowledge is power,” might be better stated in this context as “education empowers employees.” Power may be defined as the ability to influence outcomes in a particular situation, thus educational empowerment of employees may be described as the process of gaining the ability to influence work outcomes positively through increased knowledge or experience. To accomplish this objective, research institutions must assure that the personnel who care for or conduct scientific research with laboratory animals have the relevant qualifications and experience or must be provided with the appropriate training. Such training not only helps personnel to perform their job duties with confidence and competence but also potentially helps to avoid unnecessary animal pain or distress, loss of research time and effort, and wasted expenses. In addition, the provision of employee training is a legal and regulatory requirement according to US Department of Agriculture (USDA) regulations (9 CFR 1985), Public Health Service (PHS) Policy (PHS 2002), and the Guide for the Care and Use of Laboratory Animals (NRC 1996). A sustained and effective training program will also help to build a cohesive and collaborative work environment. All personnel engaged in animal care, use, or oversight must understand their respective roles in the animal research enterprise and how they complement and support each other. While scientists are primarily responsible for conducting research, the laboratory animal veterinarians, animal care technicians, and institutional animal care and use committee (IACUC) members support the scientific research in a variety of ways: by providing optimal animal care, preventing the introduction of disease, and avoiding unnecessary animal pain or distress. Educating personnel about the effects of inappropriate care and use will also help them to understand how optimal animal health and welfare directly affects the outcome of the research. In addition, it helps to assure that the institution is compliant with the relevant laws, regulations, and guidelines. Working collaboratively results in the shared goals of good science and humane animal care. “Modern laboratory animal science and medicine” (Wolfle 2003) was officially recognized almost 60 yr ago, and much has been learned about the appropriate care and use of laboratory animals during the past six decades (AALAS 1999). However, it was not until 1985 that USDA regulations and PHS Policy required training for animal care and use personnel. In 1988, to help institutions comply with the regulatory requirements and to assist them in developing training programs, the Institute of Laboratory Animal Resources (renamed in 1997 to the Institute for Laboratory Animal Research), National Research Council, appointed a Committee on Educational Programs in Laboratory Animal Science. As a result, in 1991 ILAR published Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Program was published (NRC 1991). This manual, which includes a course syllabus, training resources, and educational tools, continues to provide useful guidance for training research and animal care personnel. However, new approaches to education and training, advancements in technology, and many improvements in animal care and use have been introduced in the last 15 yr. This issue of ILAR Journal is intended to update and enhance the ILAR training manual. Leticia V. Medina, D.V.M., DACLAM, is Manager, Animal Welfare and Compliance, Preclinical Safety, Abbott Laboratories, Abbott Park, IL. Lynn C. Anderson, D.V.M., DACLAM, is Executive Director, Consulting and Staffing Services, Charles River Laboratories, Wilmington, MA. Address correspondence and reprint requests to Dr. Leticia V. Medina, Manager, Animal Welfare and Compliance, Abbott Laboratories, Preclinical Safety, R46G, AP9A-1, 100 Abbott Park Road, Abbott Park, IL 600646105, or email Letty.medina@abbott.com.

Fundamental Training for Individuals Involved in the Care and Use of Laboratory Animals: A Review and Update of the 1991 NRC Core Training Module

Public trust demands that individuals who do research, testing, or teaching with animals use humane, ethical, and scientifically sound methods. Furthermore, the Animal Welfare Act and the Public Health Service Policy require research institutions to provide basic training and to ensure that anyone who cares for and/or works with laboratory animals has the appropriate training or experience relevant to their job responsibilities. Institutions accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International must also provide training programs and ensure the qualifications of personnel. The primary goal of this training is to provide individuals with basic knowledge and to reinforce attitudes and behaviors that help to ensure humane animal care and use. This article provides an overview of the core training module outline and content from the 1991 report of the Institute for Laboratory Animal Research, Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs, as well as pertinent updates for introducing personnel to information regarding the care and use of laboratory animals. Both mandatory and suggested training topics are reviewed, including relevant regulations and standards, ethical considerations, humane methods of animal experimentation and maintenance, and other pertinent topics. Although the fundamental training course content and delivery will vary depending on the nature and complexity of an institution's animal care and use program, this basic training provides the foundation for more in-depth training programs and supports humane and ethical animal care and use.

Ethics, Standards, and Procedures of Animal and Human Chronobiology Research

The majority of research papers published in Chronobiology International report the findings of investigations conducted on laboratory animals and human beings. The editors and the readers of the journal expect the authors of submitted manuscripts to have made an important contribution to biological rhythm and related research through the ethical conduct of investigations and unbiased and accurate reporting of findings. Authors of scientific papers are required to disclose any potential conflict of interest. The journal accepts only papers that are original work, no part of which has been submitted for publication elsewhere, except as brief abstracts. The journal and its editors endorse the compliance of investigators to the principles of the Declaration of Helsinki of the World Medical Association, which relate to the conduct of ethical research on human beings, and the Guide for the Care and Use of Laboratory Animals of the Institute for Laboratory Animal Research of the National Research Council, which relate to the conduct of ethical research on laboratory and other animals. The peer review of manuscripts by Chronobiology International thus includes judgment as to whether or not the investigative methods conform to the standards of good research practice. This article updates the ethical policies, standards, and procedures for manuscripts submitted to Chronobiology International that involve human and animal biological rhythm research, both from the perspective of the criteria of quality chronobiology investigation and from the perspective of humane and ethical research on human beings and animals.

Veterinarians in Biomedical Research: A Perilous Future?

INTRODUCTION Converging events in the biomedical research arena suggest that research activities relying heavily on animal use may have expanded so much that the supply of veterinarians trained in specialties related to biomedical research is inadequate. This concern led the Institute for Laboratory Animal Research of the National Academies (ILAR) to convene a committee to study a highly relevant issue facing the biomedical research community both in academia and in industry: How can more veterinarians be prepared for careers in biomedical research? The seriousness of the issue is reflected in the diverse institutions supporting the study, including the National Institutes of Health (NIH), the American College of Laboratory Animal Medicine (ACLAM), the American Society for Pharmacology and Experimental Therapeutics, the American Veterinary Medical Association (AVME), GlaxoSmithKline, Merck and Co., and Pfizer, Inc. The ILAR study was authored by a committee of experts, chaired by Dr. James Fox, of the Massachusetts Institute of Technology. This article is based on the executive summary of the committee’s report, National Need and Priorities for Veterinarians in Biomedical Research.

Laboratory Animals and Immunization Procedures: Challenges and Opportunities

This issue of ILAR Journal presents an overview of new developments and insights in the study of immunization procedures and adjuvant products. Substantial progress has been made, both with regard to new technologies and to understanding the immune response since publication of an earlier ILAR Journal issue devoted to Adjuvants and Antibody Production (Landi 1995). It is timely and important once again to address these developments. The objective of the current ILAR Journal issue is to discuss critical aspects of immunization in the context of what is known of the immune response and to provide an overview of new developments in the production of polyclonal antibodies (PAbs) and monoclonal antibodies (MAbs). Immunizations in laboratory animals are performed for a wide variety of reasons. Primary purposes include (1) induction of specific B cells for the generation of hybridomas, (2) production of PAbs and MAbs, (3) development and quality control of immunobiological products, (4) fundamental immunological studies, and (5) induction of specific disease models. Clearly, these studies have been integral to scientific breakthroughs that have occurred in many areas of biomedical research. One such critical breakthrough has been the development of highly effective vaccines. In other cases, products such as PAbs and MAbs, which are obtained from immunization procedures, have become essential reagents in the laboratory and are being applied in diagnostic testing, in cancer therapy, and in numerous other ways. Nevertheless, despite the significant medical advances that have resulted, the use of laboratory animals for immunization procedures continues to generate controversy. Investigators and members of animal care and use committees continue to have frequent and fundamental questions related to immunization and adjuvant products. Although the answers to such questions are not always clear and unequivocal, data and information in the field of immunization have increased. Indeed, tradition and myths are gradually being replaced by science-based approaches. For example, descriptions of the adverse reactions of Freund’s complete adjuvant (FCA), which is used for its immunostimulatory capabilities, were first published in 1950 (Leskowitz and Waksman 1950) and then in 1960 (Steiner et al. 1960). Since then, discussions regarding the potential of FCA to induce pain and distress have continued for several decades and have resulted in the preparation of numerous guidelines (e.g., institutional guidelines in the United States, and regulatory guidelines in Canada and several European countries). Currently, the use of FCA is limited in experimental animals, and the process of developing alternative adjuvant products has begun. Concerning the production of MAbs, the Institute for Laboratory Animal Research (ILAR) Committee on Methods of Producing Monoclonal Antibodies concluded in 1999 that the intraperitoneal accumulation of ascites is likely to be associated with pain and distress (NRC 1999). Committee members recommended that the tissue-culture method for the production of MAbs should be adopted as the routine method unless there is clear reason why tissue culture methods cannot be used or why their use would represent an unreasonable barrier to obtaining the product at a cost consistent with the realities of funding biomedical research programs. In several European countries, the use of the ascites method is strongly discouraged, although it has not been banned entirely. As new technologies and new experimental data become available, we are gradually unraveling the complex processes underlying immunization procedures. This information will be helpful in understanding the critical aspects involved in immunization protocols and will allow us to prepare rationally based guidelines on how to design optimal immunization protocols and how to continue reducing, refining, and replacing the use of animals. In their article, McCullough and Summerfield (2005) introduce the basic concepts of the immune responses. The Coenraad F. M. Hendriksen, D.V.M., Ph.D., is an Animal Welfare Officer and Senior Scientist at the Netherlands Vaccine Institute, Bilthoven, The Netherlands.

Report on the ILAR International Workshop on the Development of Science-based Guidelines for Laboratory Animal Care

The Institute for Laboratory Animal Research of the National Academies hosted a meeting in November 2003 in Washington, DC, titled "International Workshop on the Development of Science-based Guidelines for Laboratory Animal Care." The purpose of the workshop was to bring together experts from around the world to assess the available scientific knowledge that can have an impact on the current and pending guidelines for laboratory animal care. Platform presentations focused on a variety of issues, from information exchange on mechanisms for the development of regulations across different countries and cultures, to data-based scientific studies on the effects of environmental enrichment on research outcomes. In the discussion sessions, participants were tasked with addressing the current scientific literature on the specific session topics; identifying gaps in the current knowledge in order to encourage future research endeavors; and assessing the effects of current and proposed regulations on facilities, research, and animal welfare. Participants had ample opportunities to share research outcomes and viewpoints in the multiple breakout sessions. Summaries of all breakout sessions were presented in the general session. On the final day of the workshop during the point/counterpoint session, a diverse group of speakers presented their cases for and against harmonization of standards. Although some of the speakers had serious reservations about harmonization, most of the panel members supported some form of harmonization. A positive outcome of the workshop was the opportunity for scientists and veterinarians from many countries to begin a dialogue with a goal of understanding the basis for the differences in regulatory approaches in laboratory animal care and the hope of continuing discussions on ways to work together toward some type of harmonization.

Ethical Principles and Standards for the Conduct of Human and Animal Biological Rhythm Research

Most research papers published in Chronobiology International report the findings of investigations conducted on laboratory animals and human beings. The Journal, its editors and the publication committee endorse the compliance of investigators to the principles of the Declaration of Helsinki of the World Medical Association relating to the conduct of ethical research on human beings and the Guide for the Care and Use of Laboratory Animals of the Institute for Laboratory Animal Research of the National Research Council relating to the conduct of ethical research on laboratory and other animals. Chronobiology International requires that submitted manuscripts reporting the findings of human and animal research conform to the respective policy and mandates of the Declaration of Helsinki and the Guide for the Care and Use of Laboratory Animals. The peer review of manuscripts will thus include judgment of whether or not the involved research methods conform to the standards of good research practice. This article outlines the basic expectations for the methods of human and animal biological rhythm research, both from the perspective of the fundamental criteria necessary for quality chronobiology investigation and from the perspective of humane and ethical research on human beings and animals.