Life Sciences Commons^™

Convergent And Alternative Designs For Vertebrate Suspension Feeding, S. Laurie Sanderson

S. Laurie Sanderson

In this authoritative three-volume reference work, leading researchers bring together current work to provide a comprehensive analysis of the comparative morphology, development, evolution, and functional biology of the skull.

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

Martin Stephens, PhD

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 …

Adaptation Of The Systematic Review Framework To The Assessment Of Toxicological Test Methods: Challenges And Lessons Learned With The Zebrafish Embryotoxicity Test, Martin L. Stephens, Sevcan Gül Akgün-Ölmez, Sebastian Hoffman, Rob De Vries, Burkhard Flick, Thomas Hartung, Manoj Lalu, Alexandra Maertens, Hilda Witters, Robert Wright, Katya Tsaioun

Martin Stephens, PhD

Systematic review methodology is a means of addressing specific questions through structured, consistent, and transparent examinations of the relevant scientific evidence. This methodology has been used to advantage in clinical medicine, and is being adapted for use in other disciplines. Although some applications to toxicology have been explored, especially for hazard identification, the present preparatory study is, to our knowledge, the first attempt to adapt it to the assessment of toxicological test methods. As our test case, we chose the zebrafish embryotoxicity test (ZET) for developmental toxicity and its mammalian counterpart, the standard mammalian prenatal development toxicity study, focusing the …

Welfare Challenges Influence The Complexity Of Movement: Fractal Analysis Of Behaviour In Zebrafish, Anthony G. Deakin, Joseph W. Spencer, Andrew R. Cossins, Iain S. Young, Lynne U. Sneddon

Lynne Sneddon, PhD

The ability to assess welfare is an important refinement that will ensure the good condition of animals used in experimentation. The present study investigated the impact of invasive procedures on the patterns of movement of zebrafish (Danio rerio). Recordings were made before and after fin clipping, PIT tagging and a standard pain test and these were compared with control and sham handled zebrafish. The fractal dimension (FD) from the 3D trajectories was calculated to determine the effect of these treatments on the complexity of movement patterns. While the FD of zebrafish trajectories did not differ over time in either the …

Does Environmental Enrichment Promote Recovery From Stress In Rainbow Trout?, Kieran C. Pounder, Jennifer L. Mitchell, Jack S. Thomson, Tom G. Pottinger, Jonathan Buckley, Lynne U. Sneddon

Lynne Sneddon, PhD

The EU Directive on animal experimentation suggests that all protected animals should have enrichment to improve welfare yet relatively little research has been conducted on the impact of enrichment in fish. Studies employing enrichment in zebrafish have been contradictory and all fish species should be provided with species-specific enrichments relevant to their ecology. Salmonids are important experimental models in studies within aquaculture, toxicology and natural ecosystems. This study therefore sought to establish whether an enriched environment in an experimental aquarium may promote improved welfare in rainbow trout (Oncorhynchus mykiss) by enhancing their recovery from invasive procedures. Trout were …

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

Lynne Sneddon, PhD

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 …

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

Andrew N. Rowan, DPhil

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 …

Practical Considerations In Regenerative Medicine Research: Iacucs, Ethics, And The Use Of Animals In Stem Cell Studies, Susan Vandewoude, Bernard E. Rollin

Bernard Rollin, PhD

The intent of US federal laws mandating IACUC review of animal-related activities was to satisfy contemporary socioethical concerns by introducing deliberations about ethics and animal welfare into the research process when animals are used. These laws and the system they chartered have worked well for the most part in providing opportunities for consideration of animal welfare as a vital part of animal research. As a result, investigators today are far less naïve about the ethical issues raised by research on animals and typically more sympathetic about the need for such consideration. As evidence of this growing awareness, the literature on …

Beyond Pain—Controlling Suffering In Laboratory Animals, Bernard E. Rollin

Bernard Rollin, PhD

No abstract provided.

The Animal Research Controversy: Protest, Process & Public Policy, Andrew N. Rowan, Franklin M. Loew, Joan C. Weer

Andrew N. Rowan, DPhil

The controversy today regarding the use of animals in research appears on the surface to be a strongly polarized struggle between the scientific community and the animal protection movement. However, there is a wide range of opinions and philosophies on both sides. Mistrust between the factions has blossomed while communication has withered. Through the 1960s, 1970s and early 1980s, the animal movement grew in numbers and financial resources, and developed much greater public recognition and political clout. The research community paid relatively little attention to the animal movement for much of this period but, alarmed by several public relations coups …

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

David Fraser, PhD

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

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

Troy Seidle, PhD

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 …

Mental Stress From Animal Experiments: A Survey With Korean Researchers, Minji Kang, Ahram Han, Da-Eun Kim, Troy Seidle, Kyung-Min Lim, Seungjin Bae

Troy Seidle, PhD

Animal experiments have been widely conducted in the life sciences for more than a century, and have long been a subject of ethical and societal controversy due to the deliberate infliction of harm upon sentient animals. However, the harmful use of animals may also negatively impact the mental health of researchers themselves. We sought to evaluate the anxiety level of researchers engaged in animal use to analyse the mental stress from animal testing. The State Anxiety Scale of the State-Trait Anxiety Inventory (STAI) was used to evaluate how researchers feel when they conduct animal, as opposed to non-animal, based experiments …

Non-Invasive Methods Of Identifying And Tracking Wild Squid, Ruth A. Byrne, James B. Wood, Roland C. Anderson, Ulrike Griebel, Jennifer A. Mather

Jennifer Mather, PhD

The ability to identify individual free-living animals in the field is an important method for studying their behavior. Apart from invasive external or internal tags, which may cause injury or abnormal behavior, most cephalopods cannot be tagged, as their skin is too soft and delicate for tag retention. Additionally, cephalopods remove many types of tags. However, body markings have been successfully used as a non invasive method to identify individuals of many different species of animals, including whale sharks, grey whales, seals, and zebras. We developed methods to sex and individually identify Caribbean reef squid, Sepiotheuthis sepioidea. Males showed distinct …

Animal Organs In Humans: Uncalculated Risks And Unanswered Questions, Gillian R. Langley, Joyce D'Silva

Gill Langley, PhD

This report, produced jointly by the British Union for the Abolition of Vivisection and Compassion in World Farming, fills a number of significant gaps in the current debate about xenotransplantation.

In this report we also summarise the ethical and welfare issues concerning experiments on animals for xenotransplant research and their possible use as source animals for organs. Both these aspects are responsible for much pain and distress caused to many animals. We prefer the term “source animals” to “donor animals”, because animals do not choose to donate their organs for xenotransplantation.

Application Of Fraser’S “Practical” Ethic In Veterinary Practice, And Its Compatibility With A “One Welfare” Framework, Anne Fawcett, Siobhan Mullan, Paul Mcgreevy

Paul McGreevy, PhD

Ethically challenging situations are common in veterinary practice, and they may be a source of moral stress, which may in turn impact the welfare of veterinarians. Despite recognition of the importance of ethical reasoning, some veterinary students may struggle to apply theoretical ethical frameworks. Fraser developed a “practical” ethic consisting of four principles that can be applied to ethically challenging situations. We apply Fraser’s “practical” ethic to three cases that veterinarians may encounter: animal hoarding, animal neglect, and treatment of wildlife. We argue that Fraser’s “practical” ethic is consistent with a One Welfare framework, and may have increasing currency for …

Ethical And Scientific Pitfalls Concerning Laboratory Research With Non-Human Primates, And Possible Solutions, Constança Carvalho, Augusta Gaspar, Andrew Knight, Luís Vicente

Andrew Knight, PhD

Basic and applied laboratory research, whenever intrusive or invasive, presents substantial ethical challenges for ethical committees, be it with human beings or with non-human animals. In this paper we discuss the use of non-human primates (NHPs), mostly as animal models, in laboratory based research. We examine the two ethical frameworks that support current legislation and guidelines: deontology and utilitarianism. While human based research is regulated under deontological principles, guidelines for laboratory animal research rely on utilitarianism. We argue that the utilitarian framework is inadequate for this purpose: on the one hand, it is almost impossible to accurately predict the benefits …

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

Andrew Knight, PhD

No abstract provided.

Critically Evaluating Animal Research, Andrew Knight

Andrew Knight, PhD

No abstract provided.

Contribution Of Animal Models To Contemporary Understanding Of Attention Deficit Hyperactivity Disorder, Constança Carvalho, Mariana Vieira Crespo, Luísa Ferreira Bastos, Andrew Knight, Luís Vincente

Andrew Knight, PhD

Attention Deficit Hyperactivity Disorder (ADHD) is a poorly understood neurodevelopmental disorder of multifactorial origin. Animal-based research has been used to investigate ADHD etiology, pathogenesis and treatment, but the efficacy of this research for patients has not yet been systematically evaluated. Such evaluation is important given the resource consumption and ethical concerns incurred by animal use.

We used the citation tracking facility within Web of Science to locate citations of original research papers on animal models related to ADHD published prior to 2010 identified in PubMed by relevant search terms. Human medical papers citing those animal studies were carefully analyzed by …

Bias During The Evaluation Of Animal Studies, Andrew Knight

Andrew Knight, Ph.D.

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 …

Pnaktide Attenuates Steatohepatitis And Atherosclerosis By Blocking Na/K-Atpase/Ros Amplification In C57bi6 And Apoe Knockout Mice Fed A Western Diet, K Sodhi, K Srikanthan, P Goguet-Rubio, A Nichols, A Mallick, A Nawab, R Martin, P Shah, M Chaudhry, S Sigdel, M El-Hamdani, J Liu, Z Xie, Nader Abraham, J Shapiro

Nader G. Abraham

We have previously reported that the alpha1 subunit of sodium potassium adenosine triphosphatase (Na/K-ATPase), acts as a receptor and an amplifier for reactive oxygen species, in addition to its distinct pumping function. On this background, we speculated that blockade of Na/K-ATPase-induced ROS amplification with a specific peptide, pNaKtide, might attenuate the development of steatohepatitis. To test this hypothesis, pNaKtide was administered to a murine model of NASH: the C57Bl6 mouse fed a "western" diet containing high amounts of fat and fructose. The administration of pNaKtide reduced obesity as well as hepatic steatosis, inflammation and fibrosis. Of interest, we also noted …

Ablation Of Adipose-Ho-1 Expression Increases White Fat Over Beige Fat Through Inhibition Of Mitochondrial Fusion And Of Pgc1alpha In Female Mice, S Singh, I Grant, A Meissner, A Kappas, Nader Abraham

Nader G. Abraham

Background Hmox1 plays an important role in the regulation of mitochondrial bioenergetics and function by regulating cellular heme-derived CO and bilirubin. Previous studies have demonstrated that global disruption of HO-1 in humans and mice resulted in severe organ dysfunction. Methods We investigated the potential role of adipose-specific-HO-1 genetic ablation on adipose tissue function, mitochondrial quality control and energy expenditure by generating an adipo-HO-1 knockout mouse model (Adipo-HO-1-/-) and, in vitro, adipocyte cells in which HO activity was inhibited. Adiposity, signaling proteins, fasting glucose and oxygen consumption were determined and compared to adipocyte cultures with depressed levels of both HO-1/HO-2. Results …

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

Jarrod Bailey, PhD

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

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

Jarrod Bailey, PhD

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 …

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

Jarrod Bailey, PhD

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 …

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

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

Jarrod Bailey, PhD

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 …

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

Jarrod Bailey, PhD

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 …

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

Jarrod Bailey, PhD

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 …