Organisms Commons^™

Toxicity Testing In The 21st Century: A Vision And A Strategy, Daniel Krewski, Daniel Acosta Jr, Melvin Anderson, Henry Anderson, John C. Bailar Iii, Kim Boekelheide, Robert Brent, Gail Charnley, Vivian G. Cheung, Sidney Green Jr, Karl T. Kelsey, Nancy I. Kerkvliet, Abby A. Li, Lawrence Mccray, Otto Meyer, Reid D. Patterson, William Pennie, Robert A. Scala, Gina M. Solomon, Martin Stephens, James Yager, Lauren Zeise

Martin Stephens, PhD

With the release of the landmark report Toxicity Testing in the 21st Century: A Vision and a Strategy, the U.S. National Academy of Sciences, in 2007, precipitated a major change in the way toxicity testing is conducted. It envisions increased efficiency in toxicity testing and decreased animal usage by transitioning from current expensive and lengthy in vivo testing with qualitative endpoints to in vitro toxicity pathway assays on human cells or cell lines using robotic high-throughput screening with mechanistic quantitative parameters. Risk assessment in the exposed human population would focus on avoiding significant perturbations in these toxicity pathways. Computational systems …

Pursuing Medawar’S Challenge For Full Replacement, Martin Stephens

Martin Stephens, PhD

In 1969, Nobel Prize-winning scientist Peter Medawar predicted that scientific innovation would someday fully replace the use of animals in biomedical research. Medawar correctly forecast the leveling off and subsequent decline in animal use in the last quarter of the 20th century – a period of remarkable innovation in the life sciences. A 2007 report by the U.S. National Academy of Sciences, Toxicity Testing in the 21st Century, proposed a strategy that is likely to replace all routine animal use in toxicology with innovative methods within one to two decades. Replacing animal use throughout biomedical research is more challenging given …

Personal Reflections On Russell And Burch, Frame, And The Hsus, Martin Stephens

Martin Stephens, PhD

The coincidence of anniversaries associated with the publication of William Russell and Rex Burch’s The Principles of Humane Experimental Technique, the founding of the Fund for the Replacement of Animals in Medical Experiments (FRAME), and the establishment of the collaboration between FRAME and the University of Nottingham, provides an opportunity to reflect on Russell and Burch’s legacy and how it was carried forward by FRAME. The Principles, published in 1959, was the pioneering work in what later became the alternatives or Three Rs field of replacement, reduction, and refinement of animal use. Such was the book’s initial and undeserved obscurity, …

Noncompliance With Public Health Service (Phs) Policy On Humane Care And Use Of Laboratory Animals: An Exploratory Analysis, Leah M. Gomez, Kathleen Conlee, Martin Stephens

Martin Stephens, PhD

The National Institutes of Health (NIH) is a major biomedical research-funding body in the United States. Approximately 40% of NIH-funded research involves experimentation on nonhuman animals (Monastersky, 2008). Institutions that conduct animal research with NIH funds must adhere to the Public Health Service (PHS) care and use standards of the Office of Laboratory Animal Welfare (OLAW, 2002a). Institutions deviating significantly from the PHS’s animal care and use standards must report these incidents to the NIH’s OLAW. This study is an exploratory analysis of all the significant deviations reported by animal-research facilities to OLAW during a 3-month period. The study identifies …

Addressing Distress And Pain In Animal Research: The Veterinary, Research, Societal, Regulatory And Ethical Contexts For Moving Forward, Kathleen Conlee, Martin Stephens, Andrew N. Rowan

Martin Stephens, PhD

While most people recognize that biomedical scientists are searching for knowledge that will improve the health of humans and animals, the image of someone deliberately causing harm to an animal in order to produce data that may lead to some future benefit has always prompted an uncomfortable reaction outside the laboratory. However, proponents of animal research have usually justified the practice by reference to greater benefits (new knowledge and medical treatments) over lesser costs (in animal suffering and death). Given that one of the costs of animal research is the suffering experienced by the animals, the goal of eliminating distress …

The Current Scientific And Legal Status Of Alternative Methods To The Ld50 Test For Botulinum Neurotoxin Potency Testing, Sarah Adler, Gerd Bicker, Hans Bigalke, Christopher Bishop, Jörg Blümel, Dirk Dressler, Joan Fitzgerald, Frank Gessler, Heide Heuschen, Birgit Kegel, Andreas Luch, Catherine Milne, Andrew Pickett, Heidemarie Ratsch, Irmela Ruhdel, Dorothea Sesardic, Martin Stephens, Gerhard Stiens, Peter D. Thornton, René Thürmer, Martin Vey, Horst Spielmann, Barbara Grune, Manfred Liebsch

Martin Stephens, PhD

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

Martin Stephens, PhD

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

Martin Stephens, PhD

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 …

The Minimization Of Research Animal Distress And Pain: Conclusions And Recommendations, Kathleen Conlee, Martin Stephens, Andrew N. Rowan

Martin Stephens, PhD

While the attention given to preventing, assessing, and alleviating pain in research animals has increased noticeably in recent decades, much remains to be done both in terms of implementing best practices and conducting studies to answer outstanding questions. In contrast, the attention to distress (particularly non-pain induced distress) has shown no comparable increase. There are many reasons for this discrepancy, including the conceptual untidiness of the distress concept, the paucity of pharmacological treatments for distress, and perceived lack of regulatory emphasis on distress. These are challenges that need to be addressed and overcome. This book is intended to help meet …

Resolving Animal Distress And Pain: Principles And Examples Of Good Practice In Various Fields Of Research, Alicia Karas, Matthew C. Leach, Karl A. Andrutis, Kathleen Conlee, John P. Gluck, Andrew N. Rowan, Martin L. Stephens

Martin Stephens, PhD

Pain and distress are central topics in legislation, regulations, and standards regarding the use of animals in research. However, in practice, pain has received greatly increased attention in recent years, while attention to distress has lagged far behind, especially for distress that is not induced by pain. A contributing factor is that there is less information readily available on distress, including practical information on its recognition, assessment and alleviation.

This chapter attempts to help fill that void by reversing the usual pattern and giving greater attention to distress than to pain. In addition, we also bypass the pain versus distress …