Beyond Classical Refinement Program
Beyond Classical Refinement
Coordinator: Kathrin Herrmann (kherrma1@jhu.edu) Major deficiencies in scientific rigor of animal experiments have become increasingly apparent, ultimately limiting both the reproducibility and the translatability of animal experiments to human settings. Taking into consideration insurmountable interspecies differences, solely refining animal studies will not be sufficient to advance human healthcare. Consequently, CAAT’s Refinement Program critically appraises current animal use practices in science and scrutinizes both animal and non-animal models regarding their quality and validity with the goal being improvement of science in general. To help promote the utilization of systematic reviews to reduce and replace animal use in science, CAAT’s Reduction Award funds retrospective assessments of animal models (in particular systematic reviews, meta-analyses and citation analyses) as well as other means to reduce animal use in science. The winner of the 2021 Reduction Award was Abby C. Collier, PhD, Professor of Drug Metabolism and Pharmacokinetics from the University of British Columbia for her project "In vitro-in-vivo extrapolation (IVIVE) and physiologically-based pharmacokinetic modelling." Physiological based pharmacokinetic modeling and simulation (PBPK) is a mathematical approach to taking data from a laboratory and translating it to useful approaches for deciding on drug dosages in clinical trials and chemical or environmental safety standards.
Announcement of the Winners of the 2022 CAAT Reduction Award and the CAAT Humane Education Award
Photo by Jo-Anne McArthur/ NEAVS / We Animals Media 2022 CAAT Reduction Award Congratulations to Prof. Dr. Stefan Schildknecht from Albstadt-Sigmaringen University, Germany, who won the 2022 CAAT Reduction Award for his project proposal titled “Development of an Adverse Outcome Pathway (AOP) for the relationship between ferroptosis induction and the degeneration of dopaminergic neurons”. Project summary: Ferroptosis has been identified as an iron-dependent form of cell death and can be distinguished from e.g., apoptosis or necrosis. Elevated levels of iron are a hallmark of those regions of the brain affected in Parkinson’s disease. Consequently, the hypothesis of a potential contribution of ferroptosis in Parkinson’s disease-associated neurodegeneration evolved in the scientific community. In recent years, the number of reports covering ferroptosis has expanded significantly, a clear picture of the actual contribution of ferroptosis in parkinsonian neurodegeneration however has not crystallized so far. The project focuses on the development of an “Adverse Outcome Pathway” (AOP) on the relationship between ferroptosis induction and the degeneration of neuronal subpopulations affected in parkinsonian movement disorders. An AOP represents (according to OECD guidelines) a highly structured organization of published data from the literature to allow conclusions on the presence or absence of a causal relationship between a “Molecular Initiating Event” and an “Adverse Outcome” of clinical relevance. The proposed AOP aims to: a) evaluate the strength of available knowledge on a causal correlation between ferroptosis induction and parkinsonian neurodegeneration; b) identify and highlight current knowledge gaps to guide further research efforts. The AOP hence can contribute to a reduction in animal experiments by providing a dynamic (Wiki principle) and freely available platform allowing visualization of research gaps and avoiding unnecessary reproduction of biomedical studies. 2022 CAAT Humane Education Award Congratulations to Dr. Vivian Kral and Dr. Christian Zoschke from Free University Berlin, Germany, who won the 2022 CAAT Humane Education Award for their project titled “3Rs Info Hub PRO - Your go-to place for training on non-animal research”. Project summary: The 3Rs Info Hub PRO will provide ready-to-use courses to professors in natural sciences, medicine etc., aiming to cover a wide range of applications for alternatives to animal testing. The 3Rs Info Hub PRO relies on the expertise of scientists, transforms their published methods into high-quality teaching materials, and creates complete courses for students. Thanks to the support from CAAT, the first course on brain organoids will combine lessons on human brain organoids with insights into brain anatomy and physiology, brain diseases, brain function measurements, and animal brain models. Highlights include 3D models, videos and animations based on notes from the method developers and expert interviews. Each learning unit includes an interactive quiz, which enables students to confirm their learning success independently. The ready-to-use courses will enable lecturers to teach this important topic on a high scientific and didactic level with a reasonable effort in preparation. The 3Rs Info Hub PRO course on brain organoids serves as a proof-of-concept study. Detailed evaluation results of the study will be incorporated into its continuous improvement as well as into the design of subsequent courses. Once known for its quality and scientific excellence, the 3Rs Info Hub PRO will aim to expand so that the implemented teaching materials can improve the curriculum of students around the globe. Ultimately, this will help to refute the necessity of animal tests in science, as future innovations depend on the quality of today’s teaching. Each Award includes prize money of USD 6,000. Teaching at JHU Kathrin is Faculty Co-sponsor of the Humane Sciences and Toxicology Policy Certificate. The Certificate program introduces and explains the application of the 3Rs Principles (Replacement, Reduction, and Refinement), which are the guiding principles of humane science. The Certificate also demonstrates how the use of humane science principles in biomedical research can lead to more robust scientific methodology and knowledge. The program's course of study covers the scientific principles needed to appreciate humane, human-relevant science and to identify and evaluate its implications in biomedical research and public health policy.
Other educational activities Co-organizer and co-host of the annual 3Rs Symposium, in collaboration with the USDA Animal Welfare Information Center (AWIC), NIH Office of Laboratory Animal Welfare (OLAW), and the Johns Hopkins Department of Molecular and Comparative Pathobiology. The recordings of the 2022 9th 3Rs Symposium can be viewed here . Past 3Rs Symposium videos can be viewed here in the Annual 3Rs Symposium section of the USDA National Agricultural Library. Organizer and host of the bimonthly online 3R training series in German and English that started in April 2021. The webinar series provides training to scientists, competent authority members in charge of licensing projects in the EU, members of animal experimentation committees and IACUCs and animal welfare officers. The series, which is also open to the interested public, covers best practice approaches and latest advancements in the 3Rs. In April 2021, Kathrin Herrmann started a bimonthly, free of charge 3Rs webinar series with national and international expert speakers to train scientists, competent authority members in charge of licensing projects in the EU, members of animal experimentation committees, and IACUCs and animal welfare officers. The series, which is also open to the interested public, covers best practice approaches and latest advancements in the 3Rs as well as insights into the history of animal use in research, transition science, and psychology to accelerate the much-needed paradigm change towards human-relevant, animal-free methods. Veterinarians and scientists receive educational credits, and slides and recordings are made available afterwards. The series has attracted hundreds of learners from all over the world. Recordings of the webinars are available on YouTube. Kathrin initiated a biannual early-career scientists’ workshop on NAMs in biomedical research and she hosted the first Workshop together with Helena Hogberg, CAAT’s former Deputy Director, in November 2021. The goals are to provide the newest information on human biology-based methods and to connect early career scientist so that they can support one another in this comparatively niche area of science with animals still being the default models. Recent research project In collaboration with Jarrod Bailey, (former Center for Contemporary Sciences (CCS), now Animal-free Research UK), Kathrin Herrmann co-organized and co-hosted an online Workshop on Parkinson’s disease research using NAMs. The three sessions of the PD Workshop took place on May 21, 26 and 27, 2021. The sessions were moderated by Helena Hogberg. Invited experts: Hugo Geerts, Certara, PA, USA Lise Harbom, AxoSim, LA, USA Tiago Outeiro, University of Göttingen, Germany Iosif Pediaditakis, Emulate, MA, USA Orly Reiner, Weizmann Institute of Science, Israel Stefan Schildknecht, University of Konstanz, Germany Jens Schwamborn, University of Luxembourg The proceedings were published in ALTEX. A follow-up workshop with the same group of experts is planned for November 2022.
PublicationsCassotta, M., Geerts, H., Harbom, L., Outeiro, T.F., Pediaditakis, I., Reiner, O., Schildknecht, S., Schwamborn, J.C., Bailey, J., Herrmann, K. and Hogberg, H.T., 2022. The future of Parkinson’s disease research: A new paradigm of human-specific investigation is necessary… and possible. ALTEX-Alternatives to Animal Experimentation. Available at: https://altex.org/index.php/altex/article/view/2450/2376 Carvalho, C., Herrmann, K., Marques, T. A., & Knight, A. (2021). Time to Abolish the Forced Swim Test in Rats for Depression Research?, Journal of Applied Animal Ethics Research (published online ahead of print 2021). Available at: https://doi.org/10.1163/25889567-bja10026 Busquet, F., Kleensang, A., Rovida, C., Herrmann, K., Leist, M. and Hartung, T. (2020). New European Union statistics on laboratory animal use – what really counts!, ALTEX - Alternatives to Animal Experimentation, 37(2), pp. 167-186. Available at: https://www.altex.org/index.php/altex/article/view/1755 Ormandy, E.H., Weary, D.M., Cvek, K., Fisher, M., Herrmann, K., Hobson-West, P., McDonald, M., Milsom, W., Rose, M., Rowan, A. and Zurlo, J. (2019). Animal Research, Accountability, Openness and Public Engagement: Report from an International Expert Forum. Animals, 9(9), p. 622. Available at: https://www.mdpi.com/2076-2615/9/9/622 Herrmann, K., Pistollato, F. and Stephens, M. (2019). Food For Thought...Beyond the 3Rs: Expanding the use of human-relevant replacement methods in biomedical research, ALTEX - Alternatives to Animal Experimentation, 36(3), pp. 343-352. Available at: https://www.altex.org/index.php/altex/article/view/1301 Herrmann, K. and Jayne, K., eds. (2019): Animal Experimentation: Working towards a Paradigm Change. Vol. 22, Leiden: Brill. Available at: https://brill.com/view/title/35072 Herrmann, K. (2019). Refinement on the way towards replacement: Are we doing what we can?. In: K. Herrmann and K. Jayne, eds. Animal Experimentation: Working Towards a Paradigm Change, Vol. 22, Leiden: Brill, pp. 3-64. Available at: https://brill.com/view/book/edcoll/9789004391192/BP000002.xml Herrmann, K. and Flecknell, P.A. (2019). Retrospective review of anesthetic and analgesic regimens used in animal research proposals. Alternatives to Animal Experimentation, 36(1), pp. 65-80. Available at: https://doi.org/10.14573/altex.1804011 von Aulock, S., Busquet, F., Locke, P., Herrmann, K. and Hartung, T., 2022. Engagement of scientists with the public and policymakers to promote alternative methods. ALTEX-Alternatives to a]Animal Experimentation, 39(4), pp.543-559.
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