Laboratory and Basic Science Research | Open Access Articles

A Belmont Report For Animals?, Hope Ferdowsian, L. Syd M. Johnson, Jane Johnson, Andrew Fenton, Adam Shriver, John Gluck

John P. Gluck, PhD

Human and animal research both operate within established standards. In the United States, criticism of the human research environment and recorded abuses of human research subjects served as the impetus for the establishment of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, and the resulting Belmont Report. The Belmont Report established key ethical principles to which human research should adhere: respect for autonomy, obligations to beneficence and justice, and special protections for vulnerable individuals and populations. While current guidelines appropriately aim to protect the individual interests of human participants in research, no similar, comprehensive, …

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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

Martin Stephens, PhD

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 …

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

Martin Stephens, PhD

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 …

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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

Martin Stephens, PhD

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, …

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

Lynne Sneddon, PhD

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 …

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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 …

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Acute Toxicity Testing Without Animals: More Scientific And Less Of A Gamble, Gillian R. Langley

Gill Langley, PhD

In this report, we argue specifically that acute toxicity data should not be sought from animal tests. The underlying principle of such tests on rats and mice is that the results can be effectively extrapolated to humans. In fact, after nearly 80 years of use of these tests, the predictivity of rodent data for human acute toxic effects has been disputed but never proven.

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Publication Reform To Safeguard Wildlife From Researcher Harm, Kate A. Field, Paul C. Paquet, Kyle A. Artelle, Gilbert Proulx, Ryan K. Brook, Chris T. Darimont

Chris Darimont, PhD

Despite abundant focus on responsible care of laboratory animals, we argue that inattention to the maltreatment of wildlife constitutes an ethical blind spot in contemporary animal research. We begin by reviewing significant shortcomings in legal and institutional oversight, arguing for the relatively rapid and transformational potential of editorial oversight at journals in preventing harm to vertebrates studied in the field and outside the direct supervision of institutions. Straightforward changes to animal care policies in journals, which our analysis of 206 journals suggests are either absent (34%), weak, incoherent, or neglected by researchers, could provide a practical, effective, and rapidly imposed …

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Importance Of Welfare And Ethics Competence Regarding Animals Kept For Scientific Purposes To Veterinary Students In Australia And New Zealand, Teresa Collins, Amelia Cornish, Jennifer Hood, Chris Degeling, Andrew D. Fisher, Rafael Freire, Susan J. Hazel, Jane Johnson, Jennifer K.F. Lloyd, Clive J.C. Phillips, Vicky Tzioumis, Paul D. Mcgreevy

Paul McGreevy, PhD

Veterinarians are in a strong position of social influence on animal-related issues. Hence, veterinary schools have an opportunity to raise animal health and welfare standards by improving veterinary students’ animal welfare and ethics (AWE) education, including that related to animals used for scientific purposes. A survey of 818 students in the early, mid, and senior stages of their courses at all eight veterinary schools across Australia and New Zealand was undertaken on their first day of practice (or Day One Competences) to explore how veterinary students viewed the importance of their competence in the management of welfare and ethical decision-making …

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Conscientious Objection To Harmful Animal Use Within Veterinary And Other Biomedical Education, Andrew Knight

Andrew Knight, PhD

Laboratory classes in which animals are seriously harmed or killed, or which use cadavers or body parts from ethically debatable sources, are controversial within veterinary and other biomedical curricula. Along with the development of more humane teaching methods, this has increasingly led to objections to participation in harmful animal use. Such cases raise a host of issues of importance to universities, including those pertaining to curricular design and course accreditation, and compliance with applicable animal welfare and antidiscrimination legislation. Accordingly, after detailed investigation, some universities have implemented formal policies to guide faculty responses to such cases, and to ensure that …

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Integrating Online Instruction And Hands-On Laboratory Activities For Summer Learning For Students Of Color: A Design Case In Forensic Science, Douglas Elrick, Jiaqi Yu, Connie Hargrave

Constance P. Hargrave

The popularity of TV shows such as Crime Scene Investigation (CSI) has generated high school students’ interest in forensics. Yet, forensic science is not commonly accessible to students, and especially students of color who often attend under-resourced high schools. This article presents the design, development, and evaluation of an online forensics course created for high school students of color who were a part of an informal science, technology, engineering, and mathematics (STEM) educational development program. Two essential elements guided the course design: the target learners (high school students of color) and integrating online instruction and hands-on laboratory activities involving real-world …

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An Automated Bayesian Pipeline For Rapid Analysis Of Single-Molecule Binding Data, Carlas Smith, Karina Jouravleva, Maximiliaan Huisman, Samson M. Jolly, Phillip D. Zamore, David Grünwald

David Grünwald

Single-molecule binding assays enable the study of how molecular machines assemble and function. Current algorithms can identify and locate individual molecules, but require tedious manual validation of each spot. Moreover, no solution for high-throughput analysis of single-molecule binding data exists. Here, we describe an automated pipeline to analyze single-molecule data over a wide range of experimental conditions. In addition, our method enables state estimation on multivariate Gaussian signals. We validate our approach using simulated data, and benchmark the pipeline by measuring the binding properties of the well-studied, DNA-guided DNA endonuclease, TtAgo, an Argonaute protein from the Eubacterium Thermus thermophilus. We …

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Full-Text Articles in Laboratory and Basic Science Research

A Belmont Report For Animals?, Hope Ferdowsian, L. Syd M. Johnson, Jane Johnson, Andrew Fenton, Adam Shriver, John Gluck

John P. Gluck, PhD

Martin Stephens, PhD

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

Martin Stephens, PhD

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

Martin Stephens, PhD

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

Lynne Sneddon, PhD

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

Andrew N. Rowan, DPhil

Acute Toxicity Testing Without Animals: More Scientific And Less Of A Gamble, Gillian R. Langley

Gill Langley, PhD

Publication Reform To Safeguard Wildlife From Researcher Harm, Kate A. Field, Paul C. Paquet, Kyle A. Artelle, Gilbert Proulx, Ryan K. Brook, Chris T. Darimont

Chris Darimont, PhD

Paul McGreevy, PhD

Conscientious Objection To Harmful Animal Use Within Veterinary And Other Biomedical Education, Andrew Knight

Andrew Knight, PhD

Integrating Online Instruction And Hands-On Laboratory Activities For Summer Learning For Students Of Color: A Design Case In Forensic Science, Douglas Elrick, Jiaqi Yu, Connie Hargrave

Constance P. Hargrave

An Automated Bayesian Pipeline For Rapid Analysis Of Single-Molecule Binding Data, Carlas Smith, Karina Jouravleva, Maximiliaan Huisman, Samson M. Jolly, Phillip D. Zamore, David Grünwald

David Grünwald