Life Sciences Commons^™

Animal Research, Accountability, Openness And Public Engagement: Report From An International Expert Forum, Elisabeth H. Ormandy, Daniel M. Weary, Katarina Cvek, Mark Fisher, Kathrin Herrmann, Pru Hobson-West, Michael Mcdonald, William Milsom, Margaret Rose, Andrew Rowan, Joanne Zurlo, Marina A.G. Von Keyserlingk

Oversight of Animal Experimentation Collection

In November 2013, a group of international experts in animal research policy (n = 11) gathered in Vancouver, Canada, to discuss openness and accountability in animal research. The primary objective was to bring together participants from various jurisdictions (United States, Sweden, Australia, New Zealand, Germany, Canada and the United Kingdom) to share practices regarding the governance of animals used in research, testing and education, with emphasis on the governance process followed, the methods of community engagement, and the balance of openness versus confidentiality. During the forum, participants came to a broad consensus on the need for: (a) evidence-based metrics to …

Automated Monitoring Of Behaviour In Zebrafish After Invasive Procedures, Anthony G. Deakin, Jonathan Buckley, Hamzah S. Alzu'bi, Andrew R. Cossins, Joseph W. Spencer, Waleed Al'nuaimy, Iain S. Young, Jack S. Thomson, Lynne U. Sneddon

Validation of Animal Experimentation Collection

Fish are used in a variety of experimental contexts often in high numbers. To maintain their welfare and ensure valid results during invasive procedures it is vital that we can detect subtle changes in behaviour that may allow us to intervene to provide pain-relief. Therefore, an automated method, the Fish Behaviour Index (FBI), was devised and used for testing the impact of laboratory procedures and efficacy of analgesic drugs in the model species, the zebrafish. Cameras with tracking software were used to visually track and quantify female zebrafish behaviour in real time after a number of laboratory procedures including fin …

Is Animal-Based Biomedical Research Being Used In Its Original Context?, Constança Carvalho, Daniel Alves, Andrew Knight, Luís Vicente

Validation of Animal Experimentation Collection

No abstract provided.

Critically Evaluating Animal Research, Andrew Knight

Validation of Animal Experimentation Collection

No abstract provided.

Recent Efforts To Elucidate The Scientific Validity Of Animal-Based Drug Tests By The Pharmaceutical Industry, Pro-Testing Lobby Groups, And Animal Welfare Organisations, Jarrod Bailey

Validation of Animal Experimentation Collection

Background: Even after several decades of human drug development, there remains an absence of published, substantial, comprehensive data to validate the use of animals in preclinical drug testing, and to point to their predictive nature with regard to human safety/toxicity and efficacy. Two recent papers, authored by pharmaceutical industry scientists, added to the few substantive publications that exist. In this brief article, we discuss both these papers, as well as our own series of three papers on the subject, and also various views and criticisms of lobby groups that advocate the animal testing of new drugs.

Main text: We argue …

Extrapolation Of Animal Research Data To Humans: An Analysis Of The Evidence, Rebecca Ram

Validation of Animal Experimentation Collection

The ethical arguments against animal experimentation remain ever-strong. In addition, the scientific case against the use of animals in research grows more compelling, with exponential progress in the development of alternative methods and new research technologies. The Dutch authorities recently announced an ambitious, but welcome, proposal to phase out “the use of laboratory animals in regulatory safety testing of chemicals, food ingredients, pesticides and (veterinary) medicines” by 2025, as well as “the use of laboratory animals for the release of biological products, such as vaccines” (Netherlands National Committee for the protection of animals used for scientific purposes, NCad, 2016, p. …

Recent Developments In Alternatives To Animal Testing, Katy Taylor

Application of Alternative Methods Collection

Methods that replace techniques that use live animals, or methods of testing substances without live animal use, are known as alternatives, replacements or non-animal methods. Some prefer the term advanced technologies given the fact that they often rely on more sophisticated technology and are more human- relevant than the animal test they replace (see Langley et al., 2015). There have been efforts to replace animal tests since the 1960s. Significant progress initially came in replacing animals used to diagnose human disease; to produce biological drugs (such as vaccines); and to safety test batches of these drugs as they were produced. …

The Changing Paradigm In Preclinical Toxicology: In Vitro And In Silico Methods In Liver Toxicity Evaluations, Fozia Noor

Application of Alternative Methods Collection

In vitro methods, based on human primary cells, cell lines, and genetically modified reporter cell lines, have greatly expanded the scope of in vitro toxicology. Other significant progress in the area of human-induced pluripotent stem cells (hiPSCs) (Asgari et al., 2010; Schwartz et al., 2014; Shinde et al., 2016; Shtrichman, Germanguz and Itskovitz-Eldor, 2013) is allowing the application of patient and disease-specific hiPSCs (Ghodsizadeh et al., 2010; McCracken et al., 2014; Siller et al., 2013). Moreover, the tools of precise genome editing with engineered nucleases, such as the zinc finger nucleases (zfns), the transcription activator-like effecter nucleases (talens) and, more …

How To Evaluate The Science Of Non-Human Animal Use In Biomedical Research And Testing: A Proposed Format For Debate, Ray Greek, Lisa A. Kramer

Validation of Alternative Methods Collection

Over time, the interpretation of science has occasionally been corrupted by vested interest groups, be they financially motivated or ego driven. Scientific consensus and widespread public beliefs usually catch up with the evidence, but this can take a very long time and often costs lives. The use of non-human animals in biomedical research and testing is a scientific endeavor and, as such, can and should be evaluated in light of the best science currently available. But facts that have been accepted in all areas of science are routinely ignored or called into question by well-funded, vested interest groups, compromising the …

How Can The Final Goal Of Completely Replacing Animal Procedures Successfully Be Achieved?, Christiane Baumgartl-Simons, Christiane Hohense

Validation of Alternative Methods Collection

Article 23 of European Union (EU) Directive 86/609/EEC required that Member States promote the development and validation of alternative technologies and stated that the European Commission (EC) “shall report before the end of 1987 on the possibility of modifying tests and guidelines” (European Parliament, 1986, Article 23). This Directive was replaced by Directive 2010/63/EU on the protection of animals used for scientific purposes, which now requires that Member States develop and validate alternative approaches much more precisely and specifies that the ultimate objective is the “full replacement of procedures on live animals for scientific and educational purposes, as soon as …

Replacing Animal Tests To Improve Safety For Humans, Kathy Archibald, Robert Coleman, Tamara Drake

Application of Alternative Methods Collection

In this chapter, we propose a new, pragmatic approach that could accelerate the replacement of most, if not all, regulatory animal tests with superior tests based on human biology. We also propose that changes to the requirements for safety testing, issued by the us Food and Drug Administration (fda), must be made in order to enable the use of superior new tests, which are currently disadvantaged by the outdated language of the regulations. But first, it is imperative to establish some level of understanding of the efficacy of existing animal-based methods in order to know whether any possible replacement is …

Does The Stress Inherent To Laboratory Life And Experimentation On Animals Adversely Affect Research Data?, Jarrod Bailey

Validation of Animal Experimentation Collection

Stress and distress in laboratory animals is often inherent and unavoidable. The effect of these factors on the reliability and relevance of experimental data is not sufficiently appreciated. Greater awareness, debate and discussion of this issue are urgently required.

“Everyday” Knowledge And A New Paradigm Of Animal Research, David Fraser, Jeffrey M. Spooner, Catherine A. Schuppli

Validation of Animal Experimentation Collection

Commentary on Marino and Allen (2017) The Psychology of Cows

Letter To The Editor, Jarrod Bailey

Validation of Animal Experimentation Collection

It seems clear that heeding the opinions and recommendations of experienced neuroscientists such as Professor Beuter, the well-argued probable opinion of the time-travelling Parkinson, and Grimm and Eggel’s demands for high animal welfare and honest and realistic harm–benefit analyses, will be of paramount importance for the advancement and evolution of experiments involving NHPs, particularly in neuroscience. This will benefit animals and humans alike.

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

Experimentation Collection

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 …

Expectations For Methodology And Translation Of Animal Research: A Survey Of Health Care Workers, Ari Joffe, Meredith Bara, Natalie Anton, Nathan Nobis

Experimentation Collection

Background: Health care workers (HCW) often perform, promote, and advocate use of public funds for animal research (AR); therefore, an awareness of the empirical costs and benefits of animal research is an important issue for HCW. We aim to determine what health-care-workers consider should be acceptable standards of AR methodology and translation rate to humans.

Methods: After development and validation, an e-mail survey was sent to all pediatricians and pediatric intensive care unit nurses and respiratory-therapists (RTs) affiliated with a Canadian University. We presented questions about demographics, methodology of AR, and expectations from AR. Responses of pediatricians and nurses/RTs were …

Strategic Focus On 3r Principles Reveals Major Reductions In The Use Of Animals In Pharmaceutical Toxicity Testing, Elin Törnqvist, Anita Annas, Britta Granath, Elisabeth Jalkesten, Ian Cotgreave, Mattias Öberg

Application of Alternative Methods Collection

The principles of the 3Rs, Replacement, Reduction and Refinement, are being increasingly incorporated into legislations, guidelines and practice of animal experiments in order to safeguard animal welfare. In the present study we have studied the systematic application of 3R principles to toxicological research in the pharmaceutical industry, with particular focus on achieving reductions in animal numbers used in regulatory and investigatory in vivo studies. The work also details major factors influencing these reductions including the conception of ideas, cross-departmental working and acceptance into the work process. Data from 36 reduction projects were collected retrospectively from work between 2006 and 2010. …

The Usefulness Of Systematic Reviews Of Animal Experiments For The Design Of Preclinical And Clinical Studies, Rob B.M. De Vries, Kimberley E. Weaver, Marc T. Avey, Martin Stephens, Emily S. Sena, Marlies Leenaars

Experimentation Collection

The question of how animal studies should be designed, conducted, and analyzed remains underexposed in societal debates on animal experimentation. This is not only a scientific but also amoral question. After all, if animal experiments are not appropriately designed, conducted, and analyzed, the results produced are unlikely to be reliable and the animals have in effect been wasted. In this article, we focus on one particular method to address this moral question, namely systematic reviews of previously performed animal experiments. We discuss how the design, conduct, and analysis of future (animal and human) experiments may be optimized through such systematic …

Inflammatory Findings On Species Extrapolations: Humans Are Definitely No 70-Kg Mice, Marcel Leist, Thomas Hartung

Validation of Alternative Methods Collection

Modern toxicology has embraced in vitro methods, and major hopes are based on the Omics technologies and systems biology approaches they bring along (Hartung and McBride in ALTEX 28(2):83–93, 2011; Hartung et al. in ALTEX 29(2):119–28, 2012). A culture of stringent validation has been developed for such approaches (Leist et al. in ALTEX 27(4):309–317, 2010; ALTEX 29(4):373–88, 2012a; Toxicol Res 1:8–22, 2012b), while the quality and usefulness of animal experiments have been little scrutinized. A new study (Seok et al. 2013) now shows the low predictivity of animal responses in the field of inflammation. These findings corroborate earlier findings from …

Food For Thought … Mechanistic Validation, Thomas Hartung, Sebastian Hoffman, Martin Stephens

Experimentation Collection

Validation of new approaches in regulatory toxicology is commonly defined as the independent assessment of the reproducibility and relevance (the scientific basis and predictive capacity) of a test for a particular purpose. In large ring trials, the emphasis to date has been mainly on reproducibility and predictive capacity (comparison to the traditional test) with less attention given to the scientific or mechanistic basis. Assessing predictive capacity is difficult for novel approaches (which are based on mechanism), such as pathways of toxicity or the complex networks within the organism (systems toxicology). This is highly relevant for implementing Toxicology for the 21st …

A Guide To Defining And Implementing Protocols For The Welfare Assessment Of Laboratory Animals: Eleventh Report Of The Bvaawf/Frame/Rspca/Ufaw Joint Working Group On Refinement, P. Hawkins, D. B. Morton, O. Burman, N. Dennison, P. Honess, M. Jennings, S. Lane, V. Middleton, J. V. Roughan, S. Wells, K. Westwood

Research Methodology and Laboratory Animals Collection

The refinement of husbandry and procedures to reduce animal suffering and improve welfare is an essential component of humane science. Successful refinement depends upon the ability to assess animal welfare effectively, and detect any signs of pain or distress as rapidly as possible, so that any suffering can be alleviated. This document provides practical guidance on setting up and operating effective protocols for the welfare assessment of animals used in research and testing. It sets out general principles for more objective observation of animals, recognizing and assessing indicators of pain or distress and tailoring these to individual projects. Systems for …

Assessing The Necessity Of Chimpanzee Experimentation, Andrew Knight

Experimentation Collection

No abstract provided.

Publication Bias In Reports Of Animal Stroke Studies Leads To Major Overstatement Of Efficacy, Emily Sena, H. Bart Van Der Worp, Philip M.W. Bath, David W. Howells, Malcolm Macleod

Validation of Animal Experimentation Collection

The consolidation of scientific knowledge proceeds through the interpretation and then distillation of data presented in research reports, first in review articles and then in textbooks and undergraduate courses, until truths become accepted as such both amongst “experts” and in the public understanding. Where data are collected but remain unpublished, they cannot contribute to this distillation of knowledge. If these unpublished data differ substantially from published work, conclusions may not reflect adequately the underlying biological effects being described. The existence and any impact of such “publication bias” in the laboratory sciences have not been described. Using the CAMARADES (Collaborative Approach …

Can Animal Models Of Disease Reliably Inform Human Studies?, H. Bart Van Der Worp, David W. Howells, Emily Sena, Michelle J. Porritt, Sarah Rewell, Victoria O'Collins, Malcolm Macleod

Validation of Animal Experimentation Collection

• The value of animal experiments for predicting the effectiveness of treatment strategies in clinical trials has remained controversial, mainly because of a recurrent failure of interventions apparently promising in animal models to translate to the clinic.
• Translational failure may be explained in part by methodological flaws in animal studies, leading to systematic bias and thereby to inadequate data and incorrect conclusions about efficacy.
• Failures also result because of critical disparities, usually disease specific, between the animal models and the clinical trials testing the treatment strategy.
• Systematic review and meta-analysis of animal studies may aid in the selection of the most …

Noncompliance With Public Health Service (Phs) Policy On Humane Care And Use Of Laboratory Animals: An Exploratory Analysis, Leah M. Gomez, Kathleen Conlee, Martin Stephens

Laboratory Experiments Collection

The National Institutes of Health (NIH) is a major biomedical research-funding body in the United States. Approximately 40% of NIH-funded research involves experimentation on nonhuman animals (Monastersky, 2008). Institutions that conduct animal research with NIH funds must adhere to the Public Health Service (PHS) care and use standards of the Office of Laboratory Animal Welfare (OLAW, 2002a). Institutions deviating significantly from the PHS’s animal care and use standards must report these incidents to the NIH’s OLAW. This study is an exploratory analysis of all the significant deviations reported by animal-research facilities to OLAW during a 3-month period. The study identifies …

The Scher Report On Non-Human Primate Research — Biased And Deeply Flawed, Jarrod Bailey, Katy Taylor

Experimentation Collection

The European Commission’s Scientific Committee on Health and Environmental Risks (SCHER) recently issued an Opinion on the need for non-human primate (NHP) use in biomedical research, and the possibilities of replacing NHP use with alternatives, as part of the Directive 86/609/EEC revision process. Here, we summarise our recent complaint to the European Ombudsman about SCHER’s Opinion and the entire consultation process. It is our opinion that the Working Group almost entirely failed to address its remit, and that the Group was unbalanced and contained insufficient expertise. The Opinion presumed the validity of NHP research with inadequate supporting evidence, and ignored …

Are Animal Models Predictive For Humans?, Niall Shanks, Ray Greek, Jean Greek

Validation of Animal Experimentation Collection

It is one of the central aims of the philosophy of science to elucidate the meanings of scientific terms and also to think critically about their application. The focus of this essay is the scientific term predict and whether there is credible evidence that animal models, especially in toxicology and pathophysiology, can be used to predict human outcomes. Whether animals can be used to predict human response to drugs and other chemicals is apparently a contentious issue. However, when one empirically analyzes animal models using scientific tools they fall far short of being able to predict human responses. This is …

Addressing Distress And Pain In Animal Research: The Veterinary, Research, Societal, Regulatory And Ethical Contexts For Moving Forward, Kathleen Conlee, Martin Stephens, Andrew N. Rowan

Experimentation Collection

While most people recognize that biomedical scientists are searching for knowledge that will improve the health of humans and animals, the image of someone deliberately causing harm to an animal in order to produce data that may lead to some future benefit has always prompted an uncomfortable reaction outside the laboratory. However, proponents of animal research have usually justified the practice by reference to greater benefits (new knowledge and medical treatments) over lesser costs (in animal suffering and death). Given that one of the costs of animal research is the suffering experienced by the animals, the goal of eliminating distress …

The Role Of Clinical Veterinary Medicine In The Assessment And Treatment Of Laboratory Animal Distress, V. Hampshire

Veterinary Science and Medicine Collection

It is doubtful that the scientific community will ever arrive at a consensus definition for distress as it may be attempted for the purposes of improving animal welfare in and across the myriad of research, testing and teaching facilities in the United States and throughout the minuet of protocols that exist for animals. The stakeholders in this attempt can however address most causes of physiologic distress by instituting time-honored veterinary and agrarian approaches to animal surveillance. In this manner, the majority of individuals who participate in responsible and humane animal care might be assuaged in that a condition of maximum …

The Validity Of Animal Experiments In Medical Research, Gill Langley

Experimentation Collection

Other animals, such as mice, rats, rabbits, dogs and monkeys, are widely used as surrogates for humans in fundamental medical research. This involves creating disorders in animals by chemical, surgical or genetic means, with the aim of mimicking selected aspects of human illnesses.

It is a truism that any model or surrogate is not identical to the target being modelled. So, in medical research, experiments using animals or cell cultures or even healthy volunteers instead of patients (being the target population with the target illness) will inevitably have limitations, although these will be greater or lesser depending on the model.