Animal Experimentation and Research Commons^™

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.

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 …

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 …

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 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 …

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.

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 …

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

Laboratory Experiments Collection

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 …

Towards A New Paradigm Of Non-Captive Research On Cetacean Cognition, Lori Marino, Toni Frohoff

Experimentation Collection

Contemporary knowledge of impressive neurophysiology and behavior in cetaceans, combined with increasing opportunities for studying free-ranging cetaceans who initiate sociable interaction with humans, are converging to highlight serious ethical considerations and emerging opportunities for a new era of progressive and less-invasive cetacean research. Most research on cetacean cognition has taken place in controlled captive settings, e.g., research labs, marine parks. While these environments afford a certain amount of experimental rigor and logistical control they are fraught with limitations in external validity, impose tremendous stress on the part of the captive animals, and place burdens on populations from which they are …

Ethical And Scientific Considerations Regarding Animal Testing And Research, Hope Ferdowsian, Nancy Beck

Experimentation Collection

In 1959, William Russell and Rex Burch published the seminal book, The Principles of Humane Experimental Technique, which emphasized reduction, refinement, and replacement of animal use, principles which have since been referred to as the ‘‘3 Rs’’. These principles encouraged researchers to work to reduce the number of animals used in experiments to the minimum considered necessary, refine or limit the pain and distress to which animals are exposed, and replace the use of animals with non-animal alternatives when possible. Despite the attention brought to this issue by Russell and Burch and since, the number of animals used in research …

Critical Evaluation Of The Use Of Dogs In Biomedical Research And Testing In Europe, Nina Hasiwa, Jarrod Bailey, Peter Clausing, Mardas Daneshian, Sándor Farkas, István Gyertyán, Robert Hubrecht, Werner Kobel, Goran Krummenacher, Marcel Leist, Hannes Lohi, Adám Miklósi, Frauke Ohl, Klaus Olejniczak, Georg Schmitt, Patrick Sinnett-Smith, David Smith, Kristina Wagner, James D. Yager, Joanne Zurlo, Thomas Hartung

Companion Animals as Laboratory Research Subjects Collection

Dogs are sometimes referred to as “man’s best friend” and with the increase in urbanization and lifestyle changes, dogs are seen by their owners as family members. Society expresses specific concerns about the experimental use of dogs, as they are sometimes perceived to have a special status for humans. This may appear somewhat conflicting with the idea that the intrinsic value of all animals is the same, and that also several other animal species are used in biomedical research and toxicology. This aspect and many others are discussed in an introductory chapter dealing with ethical considerations on the use of …

Examining The Regulatory Value Of Multi-Route Mammalian Acute Systemic Toxicity Studies, Troy Seidle, Pilar Prieto, Anna Bulgheroni

Experimentation Collection

Regulatory information requirements for pesticides call for submission of acute systemic toxicity data for up to three different exposure routes (oral, dermal, inhalation) for both active ingredients and formulated products. Similar multi-route testing is required in the European Union and elsewhere for industrial chemicals. To determine the value of acute toxicity testing by more than one route, oral-dermal and oralinhalation concordances among regulatory classifications were examined for large data sets of chemicals and pesticide active ingredients. Across all sectors examined, oral acute toxicity classifications for pure active substances were more severe than those derived from dermal data in more than …

The Harmful, Nontherapeutic Use Of Animals In Research Is Morally Wrong, Nathan Nobis

Experimentation Collection

It is argued that using animals in research is morally wrong when the research is nontherapeutic and harmful to the animals. This article discusses methods of moral reasoning and discusses how arguments on this and other bioethical issues might be defended and critiqued. A basic method of moral argument analysis is presented and used to show that common objections to the view that “animal research is morally wrong” fail: ie, common arguments for the view that “animal research is morally permissible” are demonstrably unsound or in need of defense. It is argued that the best explanations why harmful, nontherapeutic research …

Assessing The Necessity Of Chimpanzee Experimentation, Andrew Knight

Experimentation Collection

No abstract provided.

Systematic Review Of Chimpanzee Use In Monoclonal Antibody Research And Drug Development: 1981-2010, Raija Bettauer

Experimentation Collection

This survey examines the extent to which live chimpanzees have been used in monoclonal antibody (mAb) research and the drug approval process. The survey covers 193 scientific articles published during the years 1981-2010, as well as preclinical studies leading to the approval of mAb drugs by the Food and Drug Administration of the United States. The frequency of the articles has decreased by more than two-thirds from their highs in the late 1980’s, and the aggregate number of chimpanzees used in these studies has decreased by more than 90%.

The experimental protocols ranged from single or multiple blood draws to …

A Kenyan Perspective On The Use Of Animals In Science Education And Scientific Research In Africa And Prospects For Improvement, Charles Kimwele, Duncan Matheka, Hope Ferdowsian

Experimentation Collection

Introduction: Animal experimentation is common in Africa, a region that accords little priority on animal protection in comparison to economic and social development. The current study aimed at investigating the prevalence of animal experimentation in Kenya, and to review shortfalls in policy, legislation, implementation and enforcement that result in inadequate animal care in Kenya and other African nations. Methods: Data was collected using questionnaires, administered at 39 highly ranked academic and research institutions aiming to identify those that used animals, their sources of animals, and application of the three Rs. Perceived challenges to the use of non-animal alternatives and common …

Self-Harm In Laboratory-Housed Primates: Where Is The Evidence That The Animal Welfare Act Amendment Has Worked?, Jonathan Balcombe, Hope Ferdowsian, Debra Durham

Animal Welfare Collection

The 1985 amendment to the United States Animal Welfare Act (AWA) to promote psychological well being of primates in the laboratory represents an acknowledgment of an important welfare problem concerning nonhuman animals. How effective has this amendment been? Perhaps the best-known contributor to psychological distress in primates in the laboratory is nonsocial housing; yet, available analyses suggest that little progress has been made in avoiding single-caging of these animals. Another way to assess psychological well being is to examine rates of self-abusive behavior in laboratory primates. If the AWA has been effective, then post-AWA self-harm rates might be lower than …

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 …

An Assessment Of The Use Of Chimpanzees In Hepatitis C Research Past, Present And Future: 2. Alternative Replacement Methods, Jarrod Bailey

Experimentation Collection

The use of chimpanzees in hepatitis C virus (HCV) research was examined in the report associated with this paper (1: Validity of the Chimpanzee Model), in which it was concluded that claims of past necessity of chimpanzee use were exaggerated, and that claims of current and future indispensability were unjustifiable. Furthermore, given the serious scientific and ethical issues surrounding chimpanzee experimentation, it was proposed that it must now be considered redundant — particularly in light of the demonstrable contribution of alternative methods to past and current scientific progress, and the future promise that these methods hold. This paper builds on …

An Assessment Of The Use Of Chimpanzees In Hepatitis C Research Past, Present And Future: 1. Validity Of The Chimpanzee Model, Jarrod Bailey

Experimentation Collection

The USA is the only significant user of chimpanzees in biomedical research in the world, since many countries have banned or limited the practice due to substantial ethical, economic and scientific concerns. Advocates of chimpanzee use cite hepatitis C research as a major reason for its necessity and continuation, in spite of supporting evidence that is scant and often anecdotal. This paper examines the scientific and ethical issues surrounding chimpanzee hepatitis C research, and concludes that claims of the necessity of chimpanzees in historical and future hepatitis C research are exaggerated and unjustifiable, respectively. The chimpanzee model has several major …

The Vision Of Toxicity Testing In The 21st Century: Moving From Discussion To Action, Melvin E. Andersen, Daniel Krewski

Toxicology and Animal Models in Research Collection

Over the past year, a series on commentaries have appeared in the Toxicological Sciences Forum Series related to the 2007 National Research Council (NRC) publication, Toxicity Testing in the 21st Century: A Vision and A Strategy. The first article in the series provided an overview of the vision and was accompanied by an editorial by the three editors of Toxicological Sciences. During the past year, eight invited commentaries from the academic, industrial, and regulatory sectors have provided diverse perspectives on the vision, noted challenges to its implementation, and highlighted aspects of toxicity testing that were not addressed in …