Research Methods in Life Sciences Commons^™

Animal Carcinogenicity Studies: 2. Obstacles To Extrapolation Of Data To Humans, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Experimentation Collection

Due to limited human exposure data, risk classification and the consequent regulation of exposure to potential carcinogens has conventionally relied mainly upon animal tests. However, several investigations have revealed animal carcinogenicity data to be lacking in human predictivity. To investigate the reasons for this, we surveyed 160 chemicals possessing animal but not human exposure data within the US Environmental Protection Agency chemicals database, but which had received human carcinogenicity assessments by 1 January 2004. We discovered the use of a wide variety of species, with rodents predominating, and of a wide variety of routes of administration, and that there were …

Animal Carcinogenicity Studies: 3. Alternatives To The Bioassay, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Experimentation Collection

Conventional animal carcinogenicity tests take around three years to design, conduct and interpret. Consequently, only a tiny fraction of the thousands of industrial chemicals currently in use have been tested for carcinogenicity. Despite the costs of hundreds of millions of dollars and millions of skilled personnel hours, as well as millions of animal lives, several investigations have revealed that animal carcinogenicity data lack human specificity (i.e. the ability to identify human non-carcinogens), which severely limits the human predictivity of the bioassay. This is due to the scientific inadequacies of many carcinogenicity bioassays, and numerous serious biological obstacles, which render profoundly …

The Class B Dealer: Down And Out?, Bernard Unti

Laboratory Experiments Collection

The supply of dogs and cats to laboratories by Class B animal dealers has been a contentious matter for decades. The subject engenders heated debate whenever it surfaces, most recently in September 2005 when Senator Daniel Akaka (D-HI) proposed an amendment to the FY 2006 agriculture funding bill to withhold federal monies to research institutions that purchase animals from Class B dealers.

Cancerous Contradictions: The Mis-Regulation Of Human Carcinogens Based On Animal Data, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Experimentation Collection

The regulation of human exposures to potential carcinogens constitutes society’s most important use of animal carcinogenicity data. However, for environmental contaminants of greatest U.S. concern, we found that in most cases (58.1%; 93/160) the U.S. Environmental Protection Agency (EPA) considered the animal data inadequate to support a classification of probable human carcinogen or noncarcinogen.

The World Health Organisation’s International Agency for Research on Cancer (IARC) is a leading international authority on carcinogenicity assessments. For chemicals lacking human exposure data (the great majority), IARC classifications of identical chemicals were significantly more conservative than EPA classifications (p

Which Drugs Cause Cancer?, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Experimentation Collection

Animal tests yield misleading results.

Animal Models Of Head Trauma, Ibolja Cernak

Biomedicine and Animal Models in Research Collection

Animal models of traumatic brain injury (TBI) are used to elucidate primary and secondary sequelae underlying human head injury in an effort to identify potential neuroprotective therapies for developing and adult brains. The choice of experimental model depends upon both the research goal and underlying objectives. The intrinsic ability to study injuryinduced changes in behavior, physiology, metabolism, the blood/tissue interface, the blood brain barrier, and/or inflammatory- and immune-mediated responses, makes in vivo TBI models essential for neurotrauma research. Whereas human TBI is a highly complex multifactorial disorder, animal trauma models tend to replicate only single factors involved in the pathobiology …

The Future Of Teratology Research Is In Vitro, Jarrod Bailey, Andrew Knight, Jonathan Balcombe

Experimentation Collection

Birth defects induced by maternal exposure to exogenous agents during pregnancy are preventable, if the agents themselves can be identified and avoided. Billions of dollars and manhours have been dedicated to animal-based discovery and characterisation methods over decades. We show here, via a comprehensive systematic review and analysis of this data, that these methods constitute questionable science and pose a hazard to humans. Mean positive and negative predictivities barely exceed 50%; discordance among the species used is substantial; reliable extrapolation from animal data to humans is impossible, and virtually all known human teratogens have so far been identified in spite …

127 Million Non-Human Vertebrates Used Worldwide For Scientific Purposes In 2005, Andrew Knight

Experimentation Collection

No abstract provided.

Ld50 Testing Of Botulinum Toxin For Use As A Cosmetic, Martin L. Stephens, Michael Balls

Experimentation Collection

In 2003, the Fund for the Replacement of Animals in Medical Experiments (FRAME) revealed that the potency of botulinum toxin for use as a popular wrinkle treatment is assessed by using the LD50 Test. The endpoint in this mouse-based testing is death through suffocation. In 2004, The Humane Society of the United States (HSUS) sought to work with Allergan, the US-based manufacturer of Botox® Cosmetic, and the U.S. Food and Drug Administration (FDA), on ways to refine, reduce, and replace this LD50 testing. This article summarises The HSUS’s campaign in the United States and provides an update on FRAME’s continuing …

Chimpanzees In Research: Past, Present, And Future, Kathleen Conlee, Sarah T. Boysen

State of the Animals 2005

Although the welfare of chimpanzees encompasses many issues, this chapter addresses their use in research, including their historical and current use in the United States, ethical and scientific concerns, public opinion, international legislation, and future directions.

Non-Human Primates In Medical Research And Drug Development: A Critical Review, Jarrod Bailey

Laboratory Experiments Collection

There is much current debate surrounding the use of non-human primates (NHPs) in medical research and drug development. This review, stimulated by calls for evidence from UK-based inquiries into NHP research, takes a critical view in order to provide some important balance against papers supporting NHP research and calling for it to be expanded. We show that there is a paucity of evidence to demonstrate the positive contribution or successful translation of NHP research to human medicine, that there is a great deal of often overlooked data showing NHP research to be irrelevant, unnecessary, even hazardous to human health and …

Laboratory Routines Cause Animal Stress, Jonathan P. Balcombe, Neal D. Barnard, Chad Sandusky

Laboratory Experiments Collection

Eighty published studies were appraised to document the potential stress associated with three routine laboratory procedures commonly performed on animals: handling, blood collection, and orogastric gavage. We defined handling as any non-invasive manipulation occurring as part of routine husbandry, including lifting an animal and cleaning or moving an animal's cage. Significant changes in physiologic parameters correlated with stress (e.g., serum or plasma concentrations of corticosterone, glucose, growth hormone or prolactin, heart rate, blood pressure, and behavior) were associated with all three procedures in multiple species in the studies we examined. The results of these studies demonstrated that animals responded with …

Ideology Masquerading As Science: The Case Of Endocrine Disrupter Screening Programmes, Troy Seidle

Experimentation Collection

The global move to develop novel testing methods and strategies to identify suspected endocrine disrupting chemicals offers a unique opportunity to move away from traditional animal testing paradigms in this new area of regulatory concern. Regrettably, the programmes under development, both in the USA and internationally through the OECD, have thus far failed to consider in vitro and other nonanimal test methods as more than “pre-screening” or “priority-setting” tools in a larger, animal-based testing strategy. Validation efforts to date have focused almost exclusively on the modification of existing animal tests to detect “endocrine effects”, with no demonstrable effort to promote …

Animal Model Research: The Apples And Oranges Quandary, Kenneth J. Shapiro

Experimentation Collection

In this paper, I explore the premises underlying the problem of the evaluation of animal models. I argue that the presence of similarities and differences between the model and the modelled, although historically and currently a dominant antinomy framing evaluation, is not a bottom-line consideration. What is critical is 1) whether we learn and 2) whether we improve treatment through the animal model research. Similarity between model and modelled and the closely related concept of validity are not coterminus with these critical evaluative measures. In fact, differences between the model and modelled also can provide impetus to new understanding and …

An Evaluation Of The Us High Production Volume (Hpv) Chemical-Testing Programme: A Study In (Ir)Relevance, Redundancy And Retro Thinking, Andrew Nicholson, Jessica Sandler, Troy Seidle

Experimentation Collection

Under the US Environmental Protection Agency (EPA) High Production Volume (HPV) Challenge Programme, chemical companies have volunteered to conduct screening-level toxicity tests on approximately 2800 widely-used industrial chemicals. Participating companies are committed to providing available toxicity information to the EPA and presenting testing proposals for review by the EPA and posting on the EPA Web site as public information. People for the Ethical Treatment of Animals (PETA) and a coalition of animal protection organisations have reviewed all the test plans submitted by the participating chemical companies for compliance with the original HPV framework, as well as with animal welfare guidelines …

Trials, Tribulations, And Trends In Tumor Modeling In Mice, Joann C. L. Schuh

Biomedicine and Animal Models in Research Collection

Selection of mouse models of cancer is often based simply on availability of a mouse strain and a known compatible tumor. Frequently this results in use of tumor models long on history but short on homology and quality control. Other factors including genetics, sex, immunological status, method and site of tumor implantation, technical competence, biological activity of the tumor, protocol sequence and timing, and selection of endpoints interact to produce outcomes in tumor models. Common reliance on survival and tumor burden data in a single mouse model often skews expectations towards high remission and cure rates; a finding seldom duplicated …

Trials, Tribulations, And Trends In Tumor Modeling In Mice, Joann C. L. Schuh

Toxicology and Animal Models in Research Collection

Selection of mouse models of cancer is often based simply on availability of a mouse strain and a known compatible tumor. Frequently this results in use of tumor models long on history but short on homology and quality control. Other factors including genetics, sex, immunological status, method and site of tumor implantation, technical competence, biological activity of the tumor, protocol sequence and timing, and selection of endpoints interact to produce outcomes in tumor models. Common reliance on survival and tumor burden data in a single mouse model often skews expectations towards high remission and cure rates; a finding seldom duplicated …

Medical Training Using Simulation: Toward Fewer Animals And Safer Patients, Jonathan Balcombe

Experimentation Collection

This paper presents the current status of computer-based simulation in medicine. Recent technological advances have enabled this field to emerge from esoteric explorations in academic laboratories to commercially available simulators designed to train users to perform medical procedures from start to finish. Today, more than a dozen companies are producing virtual reality simulators and interactive manikins for training in endoscopy, laparoscopy, anaesthesia, trauma management, angiography, and needle insertion. For many of these procedures, thousands of animals are still being used in training. Yet simulation has many advantages that can transcend scientific, ethical, economic and logistical problems that arise when using …

Ethical Issues In The Use Of Animals In Biomedical And Psychopharmocological Research, John P. Gluck, Jordan Bell

Experimentation Collection

Rationale: The ethical debate concerning the use of animals in biomedical and pharmacological research continues to be replete with misunderstandings about whether animals have moral standing. Objectives: This article briefly reviews the central ethical positions and their relationship to the basic parameters of research regulation from an international perspective. The issues associated with the validation of animal models will then be discussed. Finally, suggestions for empirical ethics research will be presented. Methods: Recent literature reviews were accessed and analyzed. Results: This review summarizes the pertinent ethical and research literature. Conclusions: In summary, regardless of the ethical perspective one favors, there …

Behavioral Evaluation Of The Psychological Welfare And Environmental Requirements Of Agricultural Research Animals: Theory, Measurement, Ethics, And Practical Implications, Lesley A. King

Experimentation Collection

The welfare of agricultural research animals relies not only on measures of good health but also on the presence of positive emotional states and the absence of aversive or unpleasant subjective states such as fear, frustration, or association with pain. Although subjective states are not inherently observable, their interaction with motivational states can be measured through assessment of motivated behavior, which indicates the priority animals place on obtaining or avoiding specific environmental stimuli and thus allows conclusions regarding the impact of housing, husbandry, and experimental procedures on animal welfare. Preference tests and consumer demand models demonstrate that animal choices are …

Pain And Distress Associated With Polyclonal Antibody Production: Discussion And Recommendations, The Humane Society Of The United States

ANIMAL RESEARCH

The Humane Society of the United States (HSUS) held a workshop in August 2002 in order to develop recommendations for minimizing pain and distress associated with polyclonal antibody (Pab) production. A small group of experts in the fields of antibody production, animal welfare, in vitro alternatives, and/or regulatory compliance participated in the roundtable discussion. The workshop was a scientifically based meeting, and recommendations were based on the extensive experience of the workshop participants as well as published literature regarding the relevant issues.

Participants recognized that insufficient attention has been paid to animal welfare aspects of Pab production, in part because …

Toxicology And New Social Ethics For Animals, Bernard E. Rollin

Experimentation Collection

The issue of animal treatment has emerged as a major social concern over the past three decades. This ramified in a new ethic for animal treatment that goes beyond concern about cruelty and attempts to eliminate animal pain and suffering, whatever its source. This is evidenced by laws governing animal research in many countries. Insofar as toxicology can entail significant and prolonged animal suffering, it is at loggerheads with this new ethic. Ways are suggested for the toxicological community to put itself in harmony with the ethic and thereby preserve its autonomy.

What It Is To Be A Dog: A Qualitative Method For The Study Of Animals Other Than Humans, Kenneth J. Shapiro

Experimentation Collection

No abstract provided.

Possibilities For Refinement And Reduction: Future Improvements Within Regulatory Testing, Martin L. Stephens, Kathleen Conlee, Gina Alvino, Andrew N. Rowan

Experimentation Collection

Approaches and challenges to refining and reducing animal use in regulatory testing are reviewed. Regulatory testing accounts for the majority of animals reported in the most painful and/or distressful categories in the United States and Canada. Refinements in testing, including the use of humane endpoints, are of increasing concern. Traditional approaches to reduction (e.g., improving experimental design) are being supplemented with complementary approaches, such as the use of tier testing to eliminate some chemicals prior to in vivo testing. Technological advances in telemetry and noninvasive techniques will help decrease either the demand for animals in testing or animal suffering. Further …

Compendium Of Chemical Carcinogens By Target Organ: Results Of Chronic Bioassays In Rats, Mice, Hamsters, Dogs, And Monkeys, Lois Swirsky Gold, Neela B. Manley, Thomas H. Sloane, Jerrold M. Ward

Toxicology and Animal Models in Research Collection

Acompendiumof carcinogenesi s bioassay results organized by target organ is presented for 738 chemicals that are carcinogenic in chronic-exposure , long-term bioassays in at least 1 species. This compendium is based primarily on experiments in rats or mice; results in hamsters, monkeys, and dogs are also reported. The compendium can be used to identify chemicals that induce tumors at particular sites and to determine whether target sites are the same for chemicals positive in more than 1 species. The source of information is the Carcinogeni c Potency Database (CPDB), which includes results of 6073 experiments on 1458 chemicals (positive or …

The Ethical Limits Of Domestication: A Critique Of Henry Heffner’S Arguments, Colin Allen, Marc Bekoff, Lori Gruen

Experimentation Collection

Henry E. Heffner argues that “animals bred for research are properly viewed as animals who have successfully invaded the laboratory niche, relying heavily on kin selection to perpetuate their genes.” (1999, p. 134). This view of human–animal interactions is the cornerstone of his defense of animal experimentation in two widely-distributed papers (Heffner 1999, 2001). We argue that Heffner’s defense lacks adequate attention to ethical distinctions and principles.

Animal Research: A Review Of Developments, 1950–2000, Andrew N. Rowan, Franklin M. Loew

State of the Animals 2001

The third phase of the animal research debate started around 1950. After World War II the government became a major sponsor of scientific research, including biomedical research. The budget of the National Institutes of Health (NIH) grew dramatically and has continued to grow, with a few minor retrenchment periods, up to the present time (see Figure 1). This growth led to an enormous expansion in publicly funded research. In the private sector, the discovery of penicillin and streptomycin led to a tremendous expansion in pharmaceutical research and in the size of the prescription drug industry. These expansions in government funding …

Primate Numerical Competence: Contributions Toward Understanding Nonhuman Cognition, Sarah T. Boysen, Karen I. Hallberg

Sentience Collection

Nonhuman primates represent the most significant extant species for comparative studies of cognition, including such complex phenomena as numerical competence, among others. Studies of numerical skills in monkeys and apes have a long, though somewhat sparse history, although questions for current empirical studies remain of great interest to several fields, including comparative, developmental, and cognitive psychology; anthropology; ethology; and philosophy, to name a few. In addition to demonstrated similarities in complex information processing, empirical studies of a variety of potential cognitive limitations or constraints have provided insights into similarities and differences across the primate order, and continue to offer theoretical …

Taking Animal Welfare Seriously: Minimizing Pain And Distress In Research Animals, The Humane Society Of The United States

ANIMAL RESEARCH

Pain and distress caused by specific research models and techniques raise serious concerns for those in the animal welfare community as well as in the scientific community. Yet good estimates of how much animal pain and/or animal distress is caused by particular techniques or methods are not yet available. The HSUS has compiled a preliminary list of research models and techniques that cause pain and distress. Analyses by the USDA and HSUS indicate that the majority of the animals reported in Column E are used in various testing procedures, with vaccine testing prominent among them. More data are needed to …

The Use Of Animals In Higher Education: Problems, Alternatives, & Recommendations, Jonathan Balcombe

eBooks

Despite recent advances in technology and increasing societal concern for animals, animals continue to be exploited and killed in large numbers so that students can learn about their structure and function. Dissection may not be without its merits from an educational standpoint, if well implemented, but it appears from student surveys that it usually is not. When one considers the associated costs—animal suffering and death in the supply trade, disruption of wild animal populations, messages that tend to undermine rather than reinforce respect for life and concern for others, rising costs of animal carcasses (as compared with alternatives with longer …