Research Methods in Life Sciences Commons^™

Evolving Protocols For Research In Equitation Science, Marc Pierard, Carol Hall, Uta König Von Borstel, Alison Averis, Lesley A. Hawson, Andrew Mclean, Charlotte Nevison, Kathalijne Visser, Paul Mcgreevy

in Situ Research Models Collection

Within the emerging discipline of Equitation Science, the application of consistent methodology, including robust objective measures, is required for sound scientific evaluation. This report aims to provide an evaluation of current methodology and to propose some initial guidelines for future research. The value of research, especially that involving small sample sizes, can be enhanced by the application of consistent methodology and reporting enabling results to be compared across studies. This article includes guidelines for experimental design in studies involving the ridden horse. Equine ethograms currently used are reviewed and factors to be considered in the development of a ridden-horse ethogram …

A Role For Folk Psychology In Animal Cognition Research, Kristin Andrews

Experimentation Collection

If we consider that the field of animal cognition research began with Darwin’s stories about clever animals, we can see that over the 150 years of work done in this field, there has been a slow swing back and forth between two extreme positions. One extreme is the view that other animals are very much like us, that we can use introspection in order to understand why other animals act as they do, and that no huge interpretive leap is required to understand animal minds. On the other extreme we have the view that other animals are utterly different from …

The Ethics Of Animal Research: A Survey Of Pediatric Health Care Workers, Ari Joffe, Meredith Bara, Natalie Anton, Nathan Nobis

Experimentation Collection

Introduction: Pediatric health care workers (HCW) often perform, promote, and advocate use of public funds for animal research (AR). We aim to determine whether HCW consider common arguments (and counterarguments) in support (or not) of AR convincing.

Design: 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, support for AR, and common arguments (with their counterarguments) to justify the moral permissibility (or not) of AR. Responses are reported using standard tabulations. Responses of pediatricians and nurses/RTs were …

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

Laboratory Experiments Collection

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 …

Annotated Bibliography: Attitudes Toward Animal Research (1998-2013), Erich Yahner

BIBLIOGRAPHIES

No abstract provided.

Considering A New Paradigm For Alzheimer’S Disease Research, Gillian R. Langley

Experimentation Collection

Using Alzheimer’s disease as a case study, this review argues that it might be time to consider a new paradigm in medical research and drug discovery. The existing framework is overly dependent on often unvalidated animal models, particularly transgenic mice. Translational success remains elusive and costly late-stage drug failure is common. The conventional paradigm tends to overlook species differences and assumes that animal-based findings are generally applicable to humans. Could pathways-based research using advanced human-specific models probed with new tools, including those of systems biology, take centre stage? The current transition in chemical toxicology to a 21st-century paradigm could be …

Public Attitudes Toward Animal Research: A Review, Elisabeth H. Ormandy, Catherine A. Schuppli

Attitudes Toward Animal Research Collection

The exploration of public attitudes toward animal research is important given recent developments in animal research (e.g., increasing creation and use of genetically modified animals, and plans for progress in areas such as personalized medicine), and the shifting relationship between science and society (i.e., a move toward the democratization of science). As such, public engagement on issues related to animal research, including exploration of public attitudes, provides a means of achieving socially acceptable scientific practice and oversight through an understanding of societal values and concerns. Numerous studies have been conducted to explore public attitudes toward animal use, and more specifically …

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

Experimentation Collection

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 …

A Review Of The Institute Of Medicine’S Analysis Of Using Chimpanzees In Biomedical Research, Robert C. Jones, Ray Greek

Biomedicine and Animal Models in Research Collection

We argue that the recommendations made by the Institute of Medicine’s 2011 report, Chimpanzees in Biomedical and Behavioral Research: Assessing the Necessity, are methodologically and ethically confused. We argue that a proper understanding of evolution and complexity theory in terms of the science and ethics of using chimpanzees in biomedical research would have had led the committee to recommend not merely limiting but eliminating the use of chimpanzees in biomedical research. Specifically, we argue that a proper understanding of the difference between the gross level of examination of species and examinations on finer levels can shed light on important methodological …

A Longitudinal View Of Primate Life In Two American Laboratories, Jonathan Balcombe

Experimentation Collection

If representative of other facilities, our findings uncover serious welfare concerns for the wellbeing of primates kept in American research facilities. These animals face regular or chronic sources of pain and distress including noxious experimental and non‐experimental events and illness and injury; and severe and prolonged social disruptions. Pain relief is meager by comparison to that normally provided to humans, despite legislative requirements to minimize pain and distress and assume similarity to humans in terms of ability to experience pain and distress. Living environments are usually confinement indoors to a metal cage, often alone, and often with a minimum of …

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

Experimentation Collection

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 …

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

Experimentation Collection

No abstract provided.

State-Of-The-Art Of 3d Cultures (Organs-On-A-Chip) In Safety Testing And Pathophysiology, Natalie Alépée, Anthony Bahinski, Mardas Daneshian, Bart De Wever, Alan Goldberg, Jan Hansmann, Thomas Hartung, John Haycock, Helena T. Hogberg, Lisa Hoelting, Jens M. Kelm, Suzanne Kadereit, Emily Mcvey, Robert Landsiedel, Marcel Leist, Marc Lübberstedt, Fozia Noor, Christian Pellevoisin, Dirk Petersohn, Uwe Pfannenbecker, Kerstin Reisinger, Tzutzuy Ramirez, Barbara Rothen-Rutishauser, Monika Schäfer-Korting, Katrin Zeilinger, Marie-Gabriele Zurich

in Vitro Research Models Collection

Integrated approaches using different in vitro methods in combination with bioinformatics can (i) increase the success rate and speed of drug development; (ii) improve the accuracy of toxicological risk assessment; and (iii) increase our understanding of disease. Three-dimensional (3D) cell culture models are important building blocks of this strategy which has emerged during the last years. The majority of these models are organotypic, i.e., they aim to reproduce major functions of an organ or organ system. This implies in many cases that more than one cell type forms the 3D structure, and often matrix elements play an important role. This …

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 …

Consensus Report On The Future Of Animal-Free Systemic Toxicity Testing, Marcel Leist, Nina Hasiwa, Costanza Rovida, Mardas Daneshian, David Basketter, Ian Kimber, Harvey Clewell, Tilman Gocht, Alan Goldberg, Francois Busquet, Anna-Maria Rossi, Michael Schwarz, Martin Stephens, Rob Taalman, Thomas B. Knudsen, James Mckim, Georgina Harris, David Pamies, Thomas Hartung

Experimentation Collection

Since March 2013, animal use for cosmetics testing for the European market has been banned. This requires a renewed view on risk assessment in this field. However, in other fields as well, traditional animal experimentation does not always satisfy requirements in safety testing, as the need for human-relevant information is ever increasing. A general strategy for animal-free test approaches was outlined by the US National Research Council’s vision document for Toxicity Testing in the 21st Century in 2007. It is now possible to provide a more defined roadmap on how to implement this vision for the four principal areas of …

Observing The Unwatchable Through Acceleration Logging Of Animal Behavior, Danielle D. Brown, Roland Kays, Martin Wikelski, Rory Wilson, A. Peter Klimley

Methodology and Animal Models in Research

Behavior is an important mechanism of evolution and it is paid for through energy expenditure. Nevertheless, field biologists can rarely observe animals for more than a fraction of their daily activities and attempts to quantify behavior for modeling ecological processes often exclude cryptic yet important behavioral events. Over the past few years, an explosion of research on remote monitoring of animal behavior using acceleration sensors has smashed the decades-old limits of observational studies. Animal-attached accelerometers measure the change in velocity of the body over time and can quantify fine-scale movements and body postures unlimited by visibility, observer bias, or the …

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

Laboratory Experiments Collection

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 …

Incorporating New Technologies Into Toxicity Testing And Risk Assessment: Moving From 21st Century Vision To A Data-Driven Framework, Russell S. Thomas, Martin A. Philbert, Scott Auerbach, Barbara A. Wetmore, Michael J. Devito, Ila Cote, J. Craig Rowlands, Maurice Whelan, Sean M. Hays, Melvin E. Andersen, M.E. (Bette) Meek, Lawrence W. Reiter, Jason C. Lambert, Harvey J. Clewell Iii, Martin L. Stephens, Q. Jay Zhao, Scott C. Wesselkamper, Lynn Flowers, Edward W. Carney, Tim P. Pastoor, Dan D. Petersen, Carole L. Yauk, Andy Nong

in Vitro Research Models Collection

Based on existing data and previous work, a series of studies is proposed as a basis toward a pragmatic early step in transforming toxicity testing. These studies were assembled into a data-driven framework that invokes successive tiers of testing with margin of exposure (MOE) as the primary metric. The first tier of the framework integrates data from high-throughput in vitro assays, in vitro-to-in vivo extrapolation (IVIVE) pharmacokinetic modeling, and exposure modeling. The in vitro assays are used to separate chemicals based on their relative selectivity in interacting with biological targets and identify the concentration at which these interactions …

Can Acute Dermal Systemic Toxicity Tests Be Replaced With Oral Tests? A Comparison Of Route-Specific Systemic Toxicity And Hazard Classifications Under The Globally Harmonized System Of Classification And Labelling Of Chemicals (Ghs), Nigel P. Moore, David J. Andrew, Donald L. Bjerke, Stuart Creton, David Dreher, Thomas Holmes, Pilar Prieto, Troy Seidle, Tim G. Rowan

Experimentation Collection

Acute systemic toxicity data (LD50 values) and hazard classifications derived in the rat following oral administration and dermal application have been analysed to examine whether or not orally-derived hazard classification or LD50 values can be used to determine dermal hazard classification. Comparing the oral and dermal classifications for 335 substances derived from oral and dermal LD50 values respectively revealed 17% concordance, and indicated that 7% of substances would be classified less severely while 76% would be classified more severely if oral classifications were applied directly to the dermal route. In contrast, applying the oral LD50 values within the dermal classification …

Prolonged Pain Research In Mice: Trends In Reference To The 3rs, Jonathan Balcombe, Hope Ferdowsian, Lauren Briese

Experimentation Collection

This literature review documents trends in the use of mice in prolonged pain research, defined herein as research that subjects mice to a source of pain for at least 14 days. The total amount of prolonged pain research on mice has increased dramatically in the past decade for the 3 pain categories examined: neuropathic, inflammatory, and chronic pain. There has also been a significant rise in the number of prolonged mouse pain studies as a proportion of all mouse studies and of all mouse pain studies. The use of transgenic mice has also risen significantly in prolonged pain research, though …

Evidence-Based Toxicology For The 21st Century: Opportunities And Challenges, Martin L. Stephens, Melvin E. Andersen, Richard A. Becker, Kellyn Betts, Kim Boekelheide, Ed Carney, Robert Chapin, Dennis Devlin, Suzanne C. Fitzpatrick, John R. Fowle Iii, Patricia Harlow, Thomas Hartung, Sebastian Hoffman, Michael P. Holsapple, Abigail Jacobs, Richard Judson, Olga Naidenko, Tim Pastoor, Grace Patlewicz, Andrew Rowan, Roberta Scherer, Rashid Shaikh, Ted Simon, Douglas Wolf, Joanne Zurlo

Toxicology and Animal Models in Research Collection

The Evidence-based Toxicology Collaboration (EBTC) was established recently to translate evidence-based approaches from medicine and health care to toxicology in an organized and sustained effort. The EBTC held a workshop on “Evidence-based Toxicology for the 21st Century: Opportunities and Challenges” in Research Triangle Park, North Carolina, USA on January 24-25, 2012. The presentations largely reflected two EBTC priorities: to apply evidence-based methods to assessing the performance of emerging pathwaybased testing methods consistent with the 2007 National Research Council report on “Toxicity Testing in the 21st Century” as well as to adopt a governance structure and work processes to move that …

The Moral Status Of Invasive Animal Research, Bernard E. Rollin

Experimentation Collection

No abstract provided.

The Use Of Biomarkers Of Toxicity For Integrating In Vitro Hazard Estimates Into Risk Assessment For Humans, Bas Blaauboer, Kim Boekelheide, Harvey Clewell, Mardas Daneshian, Milou M.L. Dingemans, Alan M. Goldberg, Marjoke Heneweer, Joanna Jaworska, Nynke I. Kramer, Marcel Leist, Hasso Seibert, Emanuela Testai, Rob J. Vandebriel, James D. Yager, Joanne Zurlo

in Vitro Research Models Collection

The role that in vitro systems can play in toxicological risk assessment is determined by the appropriateness of the chosen methods, with respect to the way in which in vitro data can be extrapolated to the in vivo situation. This report presents the results of a workshop aimed at better defining the use of in vitro-derived biomarkers of toxicity (BoT) and determining the place these data can have in human risk assessment. As a result, a conceptual framework is presented for the incorporation of in vitro-derived toxicity data into the risk assessment process. The selection of BoT takes into account …

The Ban On The Use Of Chimpanzees In Biomedical Research And Testing In The Uk Should Be Made Permanent And Legally Binding, Michelle Thew, Jarrod Bailey, Michael Balls, Michelle Hudson

Laboratory Experiments Collection

The Coalition Government is currently considering how to transpose Directive 2010/63/EU on animal experimentation into UK law. The Directive bans the use of Great Apes in laboratories, but EU Member States can seek (now or, more likely, at some time in the future) a derogation from the Commission to permit such use, where this is considered essential for the preservation of the species in question or in relation to an unexpected outbreak of a life-threatening or debilitating clinical condition in human beings. Currently, the policy of the Government is not to approve any experiments on Great Apes, but it is …

Alternative Approaches For Medical Countermeasures To Biological And Chemical Terrorism And Warfare, Thomas Hartung, Joanne Zurlo

Biomedical Research and Alternative Methods Collection

The desire to develop and evaluate drugs as potential countermeasures for biological and chemical threats requires test systems that can also substitute for the clinical trials normally crucial for drug development. Animal models have limited predictivity for drug efficacy, as is well known from many disappointments in clinical trials. Traditional in vitro and in silico approaches are not really game changers here, but the substantial investment into novel tools now underway might bring about a second generation of alternative approaches. The avenue pursued focuses primarily on the development of a Human on a Chip, i.e., the combination of different three-dimensional …

Bias During The Evaluation Of Animal Studies, Andrew Knight

Morality and Ethics of Animal Experimentation Collection

My recent book entitled The Costs and Benefits of Animal Experiments seeks to answer a key question within animal ethics, namely: is animal experimentation ethically justifiable? Or, more precisely, is it justifiable within the utilitarian cost:benefit framework that fundamentally underpins most regulations governing animal experimentation? To answer this question I reviewed more than 500 scientific publications describing animal studies, animal welfare impacts, and alternative research, toxicity testing and educational methodologies. To minimise bias I focused primarily on large-scale systematic reviews that had examined the human clinical and toxicological utility of animal studies. Despite this, Dr. Susanne Prankel recently reviewed my …

Superglue Is Not Super: An Assessment Of Superglue For Suturing Tag Incisions In A Cultured Marine Fish, Vincent Raoult, Culum Brown, Jane E. Williamson

Aquaculture Collection

No abstract provided.

Accelerating The Development Of 21st-Century Toxicology: Outcome Of A Human Toxicology Project Consortium Workshop, Martin L. Stephens, Craig Barrow, Melvin E. Andersen, Kim Boekelheide, Paul L. Carmichael, Michael P. Holsapple, Mark Lafranconi

in Vitro Research Models Collection

The U.S. National Research Council (NRC) report on “Toxicity Testing in the 21st century” calls for a fundamental shift in the way that chemicals are tested for human health effects and evaluated in risk assessments. The new approach would move toward in vitro methods, typically using human cells in a high-throughput context. The in vitro methods would be designed to detect significant perturbations to “toxicity pathways,” i.e., key biological pathways that, when sufficiently perturbed, lead to adverse health outcomes. To explore progress on the report’s implementation, the Human Toxicology Project Consortium hosted a workshop on 9–10 November 2010 in Washington, …

Rational Engagement, Emotional Response, And The Prospects For Moral Progress In Animal Use “Debates”, Nathan Nobis

Animal Welfare Collection

This chapter is designed to help people rationally engage moral issues regarding the treatment of animals, specifically in experimentation, research, product testing, and education. Little “new” philosophy is offered here, strictly speaking. New arguments are unnecessary to help make progress in how people think about these issues. What is needed are improved abilities to engage the arguments already on the table, for example, stronger skills at identifying and evaluating the existing reasons given for and against conclusions on the morality of various uses of animals. To help improve these abilities, this chapter sets forth a set of basic but powerful …

Animal Research In Medical Sciences: Seeking A Convergence Of Science, Medicine, And Animal Law, John J. Pippin

Laws and Legislation Collection

As the intersection of animal law and animal research becomes congested, it is appropriate to establish the scientific context in which laws regarding the use and care of research animals will operate. There are at least three components of this context that set the terms of the debate: ethics, science, and the legal status of animals. The following discussion will not address ethics; not because it isn’t important, but because it exists along a spectrum of objective and subjective positions that are often unassailable by argument and data. I can assure you as a former animal researcher that even in …