Research Methods in Life Sciences Commons^™

Beyond The 3rs: Expanding The Use Of Human-Relevant Replacement Methods In Biomedical Research, Kathrin Herrmann, Francesca Pistollato, Martin L. Stephens

Biomedical Research and Alternative Methods Collection

This year marks the 60th anniversary of Russell and Burch’s pioneering book, The Principles of Humane Experimental Technique. Their 3Rs framework has helped to inspire humane and scientific progress in experimental technique. However, it is time to update its strategic application. The 21st century has already seen the development of promising, high-tech non-animal models, such as organs-on-a-chip and computational approaches that, in our view, will replace animals as the default option in biomedical experimentation. How fast this transition will take place will depend on the pace at which these new models are optimized to reflect the biology of humans, rather …

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

Experimental Research and Animal Welfare Collection

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 …

Retrospective Review Of Anesthetic And Analgesic Regimens Used In Animal Research Proposals, Kathrin Herrmann, Paul A. Flecknell

Experimental Research and Animal Welfare Collection

Pain has a profound effect on an animal’s wellbeing. In Germany, researchers using animals have been legally required to reduce any possible pain, suffering, distress or lasting harm to an absolute minimum since 1972. To evaluate how these provisions have been implemented in practice, an assessment of refinements to experimental techniques was conducted by retrospectively reviewing 684 surgical interventions described in 506 animal research applications that were sent to the German competent authorities for approval in 2010. This paper focuses on the efficacy of proposed anesthesia and peri- and postoperative analgesia. Postoperative analgesia was not proposed for 30% of surgeries. …

Ethics, Efficacy, And Decision-Making In Animal Research, Lawrence A. Hansen, Kori Ann Kosberg

Morality and Ethics of Animal Experimentation Collection

Few would disagree with the ethical contention that if cruelty to animals is not wrong, then nothing is wrong. In fact, it is not only wrong, but in most states in the us, it is a crime, a felony no less. And yet, intentionally inflicting pain and suffering upon animals, which meets Webster’s definition of cruelty, is routinely countenanced when vivisection (from the Latin vivi, to be alive, and secare, to cut) is performed under license for biomedical research. Deciding to embrace, or reject, or limit animal research demands our best ethical judgment; and it is complicated by factual disputes …

Human Wrongs In Animal Research: A Focus On Moral Injury And Reification, Jane Johnson, Anna Smajdor

Morality and Ethics of Animal Experimentation Collection

Using arguments derived from the work of Axel Honneth (2006), we show that animal research involves an institutionalized failure to recognize nonhuman animals that not only reifies animals but the human persons engaged in this process, diminishing the scope of their moral agency and causing moral injury. In this chapter, we begin by briefly articulating the harms to animals in research and the more conventional harms to humans that can arise as a result of animal research, before making a case for the ethical damage wrought by the failures of recognition inherent within the system of animal research. We conclude …

The Moral Status Of Animal Research Subjects In Industry: A Stakeholder Analysis, Sarah Kenehan

Morality and Ethics of Animal Experimentation Collection

The use of non-human animals (hereinafter referred to as animals) in research and testing is a widely accepted practice in many industries. Millions of animals each year are subjected to painful procedures that include everything from physical mutilation to drug addiction. According to the United States Department of Agriculture (usda), over 820,812 animals were experimented on in the United States in 2016 (usda, 2017), though this count does not include rats, mice, or birds, and dubiously relies solely on the self-reporting of laboratories (Humane Society of the United States, 2011; Keen, 2019, Chapter 10 in this Volume). Estimates suggest that …

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

Morality and Ethics of Animal Experimentation Collection

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 …

Beyond Plausibility Checks: A Case For Moral Doubt In Review Processes Of Animal Experimentation, Mara-Daria Cojocaru, Philipp Von Gall

Morality and Ethics of Animal Experimentation Collection

The fact that countries all over the world continue to develop new regulations for experimentation on non-human animals testament that this practice raises many doubts. Our aim in this chapter is to show that one important type of doubt should receive more attention: a particular type of moral doubt that could play a pivotal role in the ethical review of animal experiments. We assume that there are a range of emotions that indicate morally complex or problematic situations. When one or all of these emotions are experienced, we say that someone is experiencing moral doubt. To illustrate this point, we …

Behavioral Research On Captive Animals: Scientific And Ethical Concerns, Kimberley Jayne, Adam See

Morality and Ethics of Animal Experimentation Collection

The first half of this chapter focuses exclusively on animals that are used in laboratory behavioral research to model wild behavior, what is typically involved, problems associated with this practice, and how behavioral research has revealed scientific problems in the animal model. The second half of this chapter then addresses the ethical questions of whether scientific curiosity of animal behavior in general provides any justification for carrying out this research in this first place, with specific focus on non-human primates (nhps).

Justifiability And Animal Research In Health: Can Democratisation Help Resolve Difficulties?, Shaun Yon-Seng Khoo

Morality and Ethics of Animal Experimentation Collection

Current animal research ethics frameworks emphasise consequentialist ethics through cost-benefit or harm-benefit analysis. However, these ethical frameworks along with institutional animal ethics approval processes cannot satisfactorily decide when a given potential benefit is outweighed by costs to animals. The consequentialist calculus should, theoretically, provide for situations where research into a disease or disorder is no longer ethical, but this is difficult to determine objectively. Public support for animal research is also falling as demand for healthcare is rising. Democratisation of animal research could help resolve these tensions through facilitating ethical health consumerism or giving the public greater input into deciding …

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

Morality and Ethics of Animal Experimentation Collection

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 …

Considering Aspects Of The 3rs Principles Within Experimental Animal Biology, Lynne U. Sneddon, Lewis G. Halsey, Nic R. Bury

Biomedical Research and Alternative Methods Collection

The 3Rs – Replacement, Reduction and Refinement – are embedded into the legislation and guidelines governing the ethics of animal use in experiments. Here, we consider the advantages of adopting key aspects of the 3Rs into experimental biology, represented mainly by the fields of animal behaviour, neurobiology, physiology, toxicology and biomechanics. Replacing protected animals with less sentient forms or species, cells, tissues or computer modelling approaches has been broadly successful. However, many studies investigate specific models that exhibit a particular adaptation, or a species that is a target for conservation, such that their replacement is inappropriate. Regardless of the species …

Pain And Laboratory Animals: Publication Practices For Better Data Reproducibility And Better Animal Welfare, Larry Carbone, Jamie Austin

Laboratory Research and Animal Welfare Collection

Scientists who perform major survival surgery on laboratory animals face a dual welfare and methodological challenge: how to choose surgical anesthetics and post-operative analgesics that will best control animal suffering, knowing that both pain and the drugs that manage pain can all affect research outcomes. Scientists who publish full descriptions of animal procedures allow critical and systematic reviews of data, demonstrate their adherence to animal welfare norms, and guide other scientists on how to conduct their own studies in the field. We investigated what information on animal pain management a reasonably diligent scientist might find in planning for a successful …

Alzheimer Disease Research In The 21st Century: Past And Current Failures, New Perspectives And Funding Priorities, Francesca Pistollato, Elan L. Ohayon, Ann Lam, Gillian R. Langley, Thomas J. Novak, David Pamies, George Perry, Eugenia Trushina, Robin S.B. Williams, Alex E. Roher, Thomas Hartung, Stevan Harnad, Neal D. Barnard, Martha Clare Morris, Mei-Chun Lai, Ryan Merkley, P. Charukeshi Chandrasekera

Experimentation Collection

Much of Alzheimer disease (AD) research has been traditionally based on the use of animals, which have been extensively applied in an effort to both improve our understanding of the pathophysiological mechanisms of the disease and to test novel therapeutic approaches. However, decades of such research have not effectively translated into substantial therapeutic success for human patients. Here we critically discuss these issues in order to determine how existing human-based methods can be applied to study AD pathology and develop novel therapeutics. These methods, which include patient-derived cells, computational analysis and models, together with large-scale epidemiological studies represent novel and …

The Ethics Of Animal Research: A Survey Of The Public And Scientists In North America, Ari R. Joffe, Meredith Bara, Natalie Anton, Nathan Nobis

Morality and Ethics of Animal Experimentation Collection

Background: To determine whether the public and scientists consider common arguments (and counterarguments) in support (or not) of animal research (AR) convincing.

Methods: After validation, the survey was sent to samples of public (Sampling Survey International (SSI; Canadian), Amazon Mechanical Turk (AMT; US), a Canadian city festival and children’s hospital), medical students (two second-year classes), and scientists (corresponding authors, and academic pediatricians). We presented questions about common arguments (with their counterarguments) to justify the moral permissibility (or not) of AR. Responses were compared using Chi-square with Bonferonni correction.

Results: There were 1220 public [SSI, n = 586; AMT, n = …

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

Experimental Research and Animal Welfare Collection

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 …

Privatization Of Biomedical Research: A Short Term Answer With Long Term Consequences, Frederick Azalekor

Nebraska College Preparatory Academy: Senior Capstone Projects

Biomedical research owned by the government is now available to be owned by private institutions. This results in stagnant innovations because researchers have trouble with all the restrictions that are placed by private institutions. Privatization of biomedical research has short term positive effects but its negative effects are overarching and disastrous. One way to combat this, is for licenses to be deployed slowly with future consequences in mind.

• Privatization has short term benefits but long term disadvantages are disastrous. • To reduce damaging effect, privatization must be deployed slowly and carefully. • Patents or proprietary ownership must be given …

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

Experimental Research and Animal Welfare Collection

No abstract provided.

Lessons From Toxicology: Developing A 21st‑Century Paradigm For Medical Research, Gill Langley, Christopher P. Austin, Anil K. Balapure, Linda S. Birnbaum, John R. Bucher, Julia Fentem, Suzanne C. Fitzpatrick, John R. Fowle Iii, Robert J. Kavlock, Hiroaki Kitano, Brett A. Lidbury, Alysson R. Muotri, Shuang-Qing Peng, Dmitry Sakharov, Troy Seidle, Thales Trez, Alexander Tonevitsky, Anja Van De Stolpe, Maurice Whelan, Catherine Willett

Experimentation Collection

Biomedical developments in the 21st century provide an unprecedented opportunity to gain a dynamic systems-level and human-specific understanding of the causes and pathophysiologies of disease. This understanding is a vital need, in view of continuing failures in health research, drug discovery, and clinical translation. The full potential of advanced approaches may not be achieved within a 20th-century conceptual framework dominated by animal models. Novel technologies are being integrated into environmental health research and are also applicable to disease research, but these advances need a new medical research and drug discovery paradigm to gain maximal benefits. We suggest a new conceptual …

The Flaws And Human Harms Of Animal Experimentation, Aysha Akhtar

Morality and Ethics of Animal Experimentation Collection

Nonhuman animal (“animal”) experimentation is typically defended by arguments that it is reliable, that animals provide sufficiently good models of human biology and diseases to yield relevant information, and that, consequently, its use provides major human health benefits. I demonstrate that a growing body of scientific literature critically assessing the validity of animal experimentation generally (and animal modeling specifically) raises important concerns about its reliability and predictive value for human outcomes and for understanding human physiology. The unreliability of animal experimentation across a wide range of areas undermines scientific arguments in favor of the practice. Additionally, I show how animal …

The Multifactorial Role Of The 3rs In Shifting The Harm-Benefit Analysis In Animal Models Of Disease, Melanie L. Graham, Mark J. Prescott

Biomedical Research and Alternative Methods Collection

Ethics on animal use in science in Western society is based on utilitarianism, weighing the harms and benefits to the animals involved against those of the intended human beneficiaries. The 3Rs concept (Replacement, Reduction, Refinement) is both a robust framework for minimizing animal use and suffering (addressing the harms to animals) and a means of supporting high quality science and translation (addressing the benefits). The ambiguity of basic research performed early in the research continuum can sometimes make harm-benefit analysis more difficult since anticipated benefit is often an incremental contribution to a field of knowledge. On the other hand, benefit …

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 …

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 …

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 …

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 …

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

Experimentation Collection

No abstract provided.

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 …

A System Of Men And Not Of Laws: What Due Process Tells Us About The Deficiencies In Institutional Review Boards, Greer Donley

Articles

Governmental regulation of human subjects research involves unique agency action. It delegates power to non-expert committees, Institutional Review Boards, to decide whether research protocols are "ethical" according to vague federal regulations. Without IRB approval, the protocol cannot be investigated. The empirical evidence regarding this system demonstrates that IRBs render deeply inconsistent and inaccurate outcomes. This Article argues that the lack of due process in the IRB system is to blame for such arbitrary agency action. By juxtaposing the levels of process required for IRB approval or research with FDA new drug approval--agency action involving similar interests--this Article highlights that IRBs …

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 …