Animal Experimentation and Research Commons^™

Analyzing And Modeling The Dysfunction Of Inhibitory Neurons In Alzheimer’S Disease, Carlos Perez, Jokubas Ziburkus, Ghamim Ullah

Physics Faculty Publications

Alzheimer’s disease (AD) is characterized by the abnormal proteolytic processing of amyloid precursor protein, resulting in increased production of a self-aggregating form of beta amyloid (Aβ). Several lines of work on AD patients and transgenic mice with high Aβ levels exhibit altered rhythmicity, aberrant neuronal network activity and hyperexcitability reflected in clusters of hyperactive neurons, and spontaneous epileptic activity. Recent studies highlight that abnormal accumulation of Aβ changes intrinsic properties of inhibitory neurons, which is one of the main reasons underlying the impaired network activity. However, specific cellular mechanisms leading to interneuronal dysfunction are not completely …

Act On The Registration And Evaluation Of Chemicals (K-Reach) And Replacement, Reduction Or Refinement Best Practices, Soojin Ha, Troy Seidle, Kyung-Min Lim

Legal Regulation of Animal Research Collection

Objectives - Korea’s Act on the Registration and Evaluation of Chemicals (K-REACH) was enacted for the protection of human health and the environment in 2015. Considering that about 2000 new substances are introduced annually across the globe, the extent of animal testing requirement could be overwhelming unless regulators and companies work proactively to institute and enforce global best practices to replace, reduce or refine animal use. In this review, the way to reduce the animal use for K-REACH is discussed. Methods - Background of the enforcement of the K-REACH and its details was reviewed along with the papers and regulatory …

Arkansas Animal Science Department Report 2016, Paul Beck, Jason Apple, Shane Gadberry, Beth Kegley, Charles Rosenkrans Jr.

Arkansas Agricultural Experiment Station Research Series

No abstract provided.

Animal-Friendly Affinity Reagents: Replacing The Needless In The Haystack, A. C. Gray, S. S. Sidhu, P. C. Chandrasekera, C. F.M. Hendriksen, C. A.K. Borrebaeck

Biomedicine and Animal Models in Research Collection

The multibillion-dollar global antibody industry produces an indispensable resource but that is generated using millions of animals. Despite the irrefutable maturation and availability of animal-friendly affinity reagents (AFAs) employing na€ive B lymphocyte or synthetic recombinant technologies expressed by phage display, animal immunisation is still authorised for antibody production. Remarkably, replacement opportunities have been overlooked, despite the enormous potential reduction in animal use. Directive 2010/63/EU requires that animals are not used where alternatives exist. To ensure its implementation, we have engaged in discussions with the EU Reference Laboratory for alternatives to animal testing (EURL ECVAM) and the Directorate General for Environment …

Nemo-Like Kinase (Nlk) Is A Pathological Signaling Effector In The Mouse Heart, Ruijie Liu

Peer Reviewed Articles

Nemo-like kinase (NLK) is an evolutionary conserved serine/threonine protein kinase implicated in development, proliferation and apoptosis regulation. Here we identified NLK as a gene product induced in the hearts of mice subjected to pressure overload or myocardial infarction injury, suggesting a potential regulatory role with pathological stimulation to this organ. To examine the potential functional consequences of increased NLK levels, cardiac-specific transgenic mice with inducible expression of this gene product were generated, as well as cardiac-specific Nlk gene-deleted mice. NLK transgenic mice demonstrated baseline cardiac hypertrophy, dilation, interstitial fibrosis, apoptosis and progression towards heart failure in response to two surgery-induced …

Chimpanzee Research: An Examination Of Its Contribution To Biomedical Knowledge And Efficacy In Combating Human Diseases, Jarrod Bailey, Jonathan Balcombe, Theodora Capaldo

Jonathan Balcombe, PhD

Research on captive chimpanzees incurs considerable animal welfare, ethical and financial costs. Advocates of such research claim these costs are outweighed by substantial advancements in biomedical knowledge, and that the genetic similarity of chimpanzees to humans enables the former to make critical contributions to preventing, diagnosing and combating human diseases. To assess these claims, we examined the disciplines investigated in 749 studies of captive chimpanzees published from 1995-2004 inclusive, and subjected 95 randomly selected papers to a detailed citation analysis:

49.5% (47/95) of papers had not been cited at the time of this study; 38.5% (34/95) were cited by 116 …

An Examination Of Chimpanzee Use In Human Cancer Research, Jarrod Bailey

Jarrod Bailey, PhD

Advocates of chimpanzee research claim the genetic similarity of humans and chimpanzees make them an indispensable research tool to combat human diseases. Given that cancer is a leading cause of human death worldwide, one might expect that if chimpanzees were needed for, or were productive in, cancer research, then they would have been widely used. This comprehensive literature analysis reveals that chimpanzees have scarcely been used in any form of cancer research, and that chimpanzee tumours are extremely rare and biologically different from human cancers. Often, chimpanzee citations described peripheral use of chimpanzee cells and genetic material in predominantly human …

An Analysis Of The Use Of Dogs In Predicting Human Toxicology And Drug Safety, Jarrod Bailey, Michelle Thew, Michael Balls

Jarrod Bailey, PhD

Dogs remain the main non-rodent species in preclinical drug development. Despite the current dearth of new drug approvals and meagre pipelines, this continues, with little supportive evidence of its value or necessity. To estimate the evidential weight provided by canine data to the probability that a new drug may be toxic to humans, we have calculated Likelihood Ratios (LRs) for an extensive dataset of 2,366 drugs with both animal and human data, including tissue-level effects and Medical Dictionary for Regulatory Activities (MedDRA) Level 1–4 biomedical observations. The resulting LRs show that the absence of toxicity in dogs provides virtually no …

Non-Human Primates In Neuroscience Research: The Case Against Its Scientific Necessity, Jarrod Bailey, Katy Taylor

Jarrod Bailey, PhD

Public opposition to non-human primate (NHP) experiments is significant, yet those who defend them cite minimal harm to NHPs and substantial human benefit. Here we review these claims of benefit, specifically in neuroscience, and show that: a) there is a default assumption of their human relevance and benefit, rather than robust evidence; b) their human relevance and essential contribution and necessity are wholly overstated; c) the contribution and capacity of non-animal investigative methods are greatly understated; and d) confounding issues, such as species differences and the effects of stress and anaesthesia, are usually overlooked. This is the case in NHP …

Monkey-Based Research On Human Disease: The Implications Of Genetic Differences, Jarrod Bailey

Jarrod Bailey, PhD

Assertions that the use of monkeys to investigate human diseases is valid scientifically are frequently based on a reported 90–93% genetic similarity between the species. Critical analyses of the relevance of monkey studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for monkeys to constitute good models for research, and that monkey data do not translate well to progress in clinical practice for humans. Salient examples include the failure of new drugs in clinical trials, the highly different infectivity and pathology of SIV/HIV, and poor extrapolation of research on Alzheimer’s disease, Parkinson’s …

An Assessment Of The Role Of Chimpanzees In Aids Vaccine Research, Jarrod Bailey

Jarrod Bailey, PhD

Prior to Simian Immunodeficiency Virus (SIV)-infected macaques becoming the ‘model of choice’ in the 1990s, chimpanzees were widely used in AIDS vaccine research and testing. Faced with the continued failure to develop an effective human vaccine, some scientists are calling for a return to their widespread use. To assess the past and potential future contribution of chimpanzees to AIDS vaccine development, databases and published literature were systematically searched to compare the results of AIDS vaccine trials in chimpanzees with those of human clinical trials, and to determine whether the chimpanzee trials were predictive of the human response. Protective and/or therapeutic …

Lessons From Chimpanzee-Based Research On Human Disease: The Implications Of Genetic Differences, Jarrod Bailey

Jarrod Bailey, PhD

Assertions that the use of chimpanzees to investigate human diseases is valid scientifically are frequently based on a reported 98–99% genetic similarity between the species. Critical analyses of the relevance of chimpanzee studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for the chimpanzee to constitute a good model for research, and furthermore, that chimpanzee data do not translate well to progress in clinical practice for humans. Leading examples include the minimal citations of chimpanzee research that is relevant to human medicine, the highly different pathology of HIV/AIDS and hepatitis C virus …

Animal Carcinogenicity Studies: Implications For The Reach System, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, PhD

The 2001 European Commission proposal for the Registration, Evaluation and Authorisation of Chemicals (REACH) aims to improve public and environmental health by assessing the toxicity of, and restricting exposure to, potentially toxic chemicals. The greatest benefits are expected to accrue from decreased cancer incidences. Hence the accurate identification of chemical carcinogens must be a top priority for the REACH system. Due to a paucity of human clinical data, the identification of potential human carcinogens has conventionally relied on animal tests. However, our survey of the US Environmental Protection Agency’s (EPA’s) toxic chemicals database revealed that, for a majority of the …

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

Jarrod Bailey, PhD

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 …

Animal Carcinogenicity Studies: 1. Poor Human Predictivity, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, PhD

The regulation of human exposure to potentially carcinogenic chemicals constitutes society’s most important use of animal carcinogenicity data. Environmental contaminants of greatest concern within the USA are listed in the Environmental Protection Agency’s (EPA’s) Integrated Risk Information System (IRIS) chemicals database. However, of the 160 IRIS chemicals lacking even limited human exposure data but possessing animal data that had received a human carcinogenicity assessment by 1 January 2004, we found that in most cases (58.1%; 93/160), the EPA considered animal carcinogenicity data inadequate to support a classification of probable human carcinogen or non-carcinogen. For the 128 chemicals with human or …

Predicting Human Drug Toxicity And Safety Via Animal Tests: Can Any One Species Predict Drug Toxicity In Any Other, And Do Monkeys Help?, Jarrod Bailey, Michelle Thew, Michael Balls

Jarrod Bailey, PhD

Animals are still widely used in drug development and safety tests, despite evidence for their lack of predictive value. In this regard, we recently showed, by producing Likelihood Ratios (LRs) for an extensive data set of over 3,000 drugs with both animal and human data, that the absence of toxicity in animals provides little or virtually no evidential weight that adverse drug reactions will also be absent in humans. While our analyses suggest that the presence of toxicity in one species may sometimes add evidential weight for risk of toxicity in another, the LRs are extremely inconsistent, varying substantially for …

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

Jarrod Bailey, PhD

Animal tests yield misleading results.

An Analysis Of The Use Of Animal Models In Predicting Human Toxicology And Drug Safety, Jarrod Bailey, Michelle Thew, Michael Balls

Jarrod Bailey, PhD

Animal use continues to be central to preclinical drug development, in spite of a lack of its demonstrable validity. The current nadir of new drug approvals and the drying-up of pipelines may be a direct consequence of this. To estimate the evidential weight given by animal data to the probability that a new drug may be toxic to humans, we have calculated Likelihood Ratios (LRs) for an extensive data set of 2,366 drugs, for which both animal and human data are available, including tissue-level effects and MedDRA Level 1–4 biomedical observations. This was done for three preclinical species (rat, mouse …

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

Jarrod Bailey, PhD

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

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

Jarrod Bailey, PhD

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 …

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

Marc Bekoff, PhD

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.

Separating Oil From Water: Suspension-Feeding Goldfish Ingest Liquid Vegetable Oil, Kristin Edwards, Gary Rice, S. Laurie Sanderson

Arts & Sciences Articles

We show that goldfish (Carassius auratus) voluntarily ingest liquid canola oil at the surface of the water and can swallow significant quantities of oil. The ability of fish to separate floating oil from water has not been tested previously, and the mechanisms used to retain oil in the form of suspended droplets, globules, or a surface film are unknown. Chromatograms of fatty acid methyl esters (FAMEs) prepared from gut samples confirmed that goldfish were able to obtain a substantial proportion of their daily lipid intake from canola oil at the surface of laboratory aquaria. Quantification of goldfish suspension-feeding, …

A Murine Model Of Inflammation-Induced Cerebral Microbleeds, Rachita K. Sumbria, Mher Mahoney Grigoryan, Vitaly Vasilevko, Tatiana B. Krasieva, Miriam Scadeng, Alexandra K. Dvornikova, Annlia Paganini-Hill, Ronald Kim, David H. Cribbs, Mark J. Fisher

Pharmacy Faculty Articles and Research

Background: Cerebral microhemorrhages (CMH) are tiny deposits of blood degradation products in the brain and are pathological substrates of cerebral microbleeds. The existing CMH animal models are β-amyloid-, hypoxic brain injury-, or hypertension-induced. Recent evidence shows that CMH develop independently of hypoxic brain injury, hypertension, or amyloid deposition and CMH are associated with normal aging, sepsis, and neurodegenerative conditions. One common factor among the above pathologies is inflammation, and recent clinical studies show a link between systemic inflammation and CMH. Hence, we hypothesize that inflammation induces CMH development and thus, lipopolysaccharide (LPS)-induced CMH may be an appropriate model to …

Institutional Animal Care And Use Committees: A Flawed Paradigm Or Work In Progress?, John P. Gluck, F. Barbara Orlans

John P. Gluck, PhD

In his challenging article, Steneck (1997) criticized the creation of the Institutional Animal Care and Use Committee (IACUC) system established by the 1985 amendments to the Animal Welfare Act. He saw the IACUC review and approval of biomedical and behavioral research with animals as an unnecessary "reassignment" of duties from existing animal care programs to IACUC committees. He argued that the committees are unable to do the work expected of them for basically three reasons: (a) the membership lacks the expertise in matters relevant to animal research and care, (b) there exists an inherent and disabling conflict of interest, and …

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

John P. Gluck, PhD

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 …

Harry F. Harlow And Animal Research: Reflection On The Ethical Paradox, John P. Gluck

John P. Gluck, PhD

With respect to the ethical debate about the treatment of animals in biomedical and behavioral research, Harry F. Harlow represents a paradox. On the one hand, his work on monkey cognition and social development fostered a view of the animals as having rich subjective lives filled with intention and emotion. On the other, he has been criticized for the conduct of research that seemed to ignore the ethical implications of his own discoveries. The basis of this contradiction is discussed and propositions for current research practice are presented.

Moving Beyond The Welfare Standard Of Psychological Well-Being For Nonhuman Primates: The Case Of Chimpanzees, John P. Gluck

John P. Gluck, PhD

Since 1985, the US Animal Welfare Act and Public Health Service policy have required that researchers using nonhuman primates in biomedical and behavioral research develop a plan ‘‘for a physical environment adequate to promote the psychological well-being of primates.’’ In pursuing this charge, housing attributes such as social companionship, opportunities to express species-typical behavior, suitable space for expanded locomotor activity, and nonstressful relationships with laboratory personnel are dimensions that have dominated the discussion. Regulators were careful not to direct a specific set of prescriptions (i.e., engineering standards) for the attainment of these goals, but to leave the design of the …

Gender Differences In Attitudes Toward Animal Research, Jennifer J. Eldridge, John P. Gluck

John P. Gluck, PhD

Although gender differences in attitudes toward animal research have been reported in the literature for some time, exploration into the nature of these differences has received less attention. This article examines gender differences in responses to a survey of attitudes toward the use of animals in research. The survey was completed by college students and consisted of items intended to tap different issues related to the animal research debate. Results indicated that women were more likely than men to support tenets of the animal protection movement. Likewise, women were more likely than men to favor increased restrictions on animal use …

Rethinking The Ethics Of Research Involving Nonhuman Animals: Introduction, Tom L. Beauchamp, Hope Ferdowsian, John P. Gluck

John P. Gluck, PhD

No abstract provided.

Animals In Biomedical Research: The Undermining Effect Of The Rhetoric Of The Besieged, John P. Gluck, Steven R. Kubacki

John P. Gluck, PhD

It is correctly asserted that the intensity of the current debate over the use of animals in biomedical research is unprecedented. The extent of expressed animosity and distrust has stunned many researchers. In response, researchers have tended to take a strategic defensive posture, which involves the assertation of several abstract positions that serve to obstruct resolution of the debate. Those abstractions include the notions that the animal protection movement is trivial and purely anti-intellectual in scope, that all science is good (and some especially so), and the belief that an ethical consensus can never really be reached between the parties.