60 Years of the 3Rs symposium: Lessons learned and the road ahead
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Abstract
When The Principles of Humane Experimental Technique was published in 1959, authors William Russell and Rex Burch had a modest goal: to make researchers think about what they were doing in the laboratory – and to do it more humanely. Sixty years later, their groundbreaking book was celebrated for inspiring a revolution in science and launching a new field: The 3Rs of alternatives to animal experimentation. On November 22, 2019, some pioneering and leading scientists and researchers in the field gathered at the Johns Hopkins Bloomberg School of Public Health in Baltimore for the 60 Years of the 3Rs Symposium: Lessons Learned and the Road Ahead. The event was sponsored by the Johns Hopkins Center for Alternatives to Animal Testing (CAAT), the Foundation for Chemistry Research and Initiatives, the Alternative Research & Development Foundation (ARDF), the American Cleaning Institute (ACI), the International Fragrance Association (IFRA), the Institute for In Vitro Sciences (IIVS), John “Jack” R. Fowle III, and the Society of Toxicology (SoT). Fourteen presentations shared the history behind the groundbreaking publication, international efforts to achieve its aims, stumbling blocks to progress, as well as remarkable achievements. The day was a tribute to Russell and Burch, and a testament to what is possible when people from many walks of life – science, government, and industry – work toward a common goal.
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William Russell and Rex Burch published their book The Principles of Humane Experimental Technique in 1959. The book encouraged researchers to replace animal experiments where it was possible, to refine experiments with animals in order to reduce their suffering, and to reduce the number of animals that had to be used for experiments to the minimum. Sixty years later, a group of pioneering and leading scientists and researchers in the field gathered to share how the publication came about and how the vision inspired international collaborations and successes on many different levels including new laws. The paper includes an overview of important milestones in the history of alternatives to animal experimentation.
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Balls, M., Goldberg, A. M., Fentem, J. H. et al. (1995). The Three Rs: The way forward. The report and recommendations of ECVAM workshop 11. Altern Lab Anim 23, 838-866.
Balls, M. (2007). Professor W.M.S. Russell (1925-2006): Doyen of the Three Rs. AATEX 14, Spec Issue, 1-7. https://www.asas.or.jp/jsaae/jsaae/zasshi/WC6_PC/paper1.pdf
Balls, M. (2009). The origins and early days of the Three Rs concept. Altern Lab Anim 37, 255-265. doi:10.1177/026119290903700306
Balls, M. (2015). 19. Russell and Burch after 1959. Altern Lab Anim 43, P59-P60. doi:10.1177/026119291504300518
Balls, M., Combes, R. and Worth, A. (eds) (2019). The History of Alternative Test Methods in Toxicology. London, UK: Academic Press/Elsevier.
Bass, R., Günzel, P., Henschler, D. et al. (1982). LD50 versus acute toxicity. Arch Toxicol 51, 183-186. doi:10.1007/BF00348850
Bass, R. (1986). EEC/CPMP. In D. Schuppan, A. D., Dayan, and F. A. Charlesworth (eds), The Contribution of Acute Toxicity Testing to the Evaluation of Pharmaceuticals. Berlin, Heidelberg, Germany: Springer. doi:10.1007/978-3-642-70390-4_8
Busquet, F., Kleensang, A., Rovida, C. et al. (2020). New European Union statistics on laboratory animal use – What really counts! ALTEX 37, 167-186. doi:10.14573/altex.2003241
Clingerman, K. J. (1990). The LD50 (Median Lethal Dose) and LC50 (Median Lethal Concentration) Toxicity Tests, January 1980 - August 1990. Beltsville, MD, USA: National Agricultural Library.
Curren, R. D. (2014). Cooperation between the United States Environmental Protection Agency and industry to develop an in vitro ocular hazard testing strategy. In Science and the Law: Analytical Data in Support of Regulation in Health, Food, and the Environment (111-118). ACS Symposium Series. doi:10.1021/bk-2014-1167.ch008
Executive Committee of the Congress (2009). Background to the Three Rs Declaration of Bologna, as Adopted by the 3rd World Congress on Alternatives and Animal Use in the Life Sciences, Bologna, Italy, on 31 August 1999: Prepared by the Executive Committee of the Congress. Altern Lab Anim 37, 285-289. doi:10.1177/026119290903700310
Grimm, H., Biller-Andorno, N., Buch, T. et al. (2023). Advancing the 3Rs: Innovation, implementation, ethics and society. Front Vet Sci 10, 1185706. doi:10.3389/fvets.2023.1185706
Harrill, A., Carstens, K., Sipes, N. et al. (2024). Validation, qualification, and regulatory acceptance of new approach methodologies - A report of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Validation Workgroup (VWG). https://cfpub.epa.gov/si/si_public_file_download.cfm?p_download_id=548786&Lab=CCTE
Hartung, T. (2021). Pyrogen testing revisited on occasion of the 25th anniversary of the whole blood monocyte activation test. ALTEX 38, 3-19. doi:10.14573/altex.2101051
Herrmann, K. and Flecknell, P. A. (2018a). Severity classification of surgical procedures and application of health monitoring strategies in animal research proposals – A retrospective review. Altern Lab Anim 46, 273-289. doi:10.1177/026119291804600
Herrmann, K. and Flecknell, P. A. (2018b). Application of humane endpoints and humane killing methods in animal research applications – A retrospective review. Altern Lab Anim 46, 317-333. doi:10.1177/026119291804600606
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 (3-64). Vol. 22. Leiden, The Netherlands: Brill. doi:10.1163/9789004391192_002
Herrmann, K. and Flecknell, P. A. (2019). Retrospective review of anesthetic and analgesic regimens used in animal research proposals. ALTEX 36, 65-80. doi:10.14573/altex.1804011
Herrmann, K. and Jayne, K. (2019). Animal Experimentation: Working towards a Paradigm Change (752). Vol. 22. Leiden, The Netherlands: Brill. doi:10.1163/9789004391192
Hubrecht, R. C. and Carter, E. (2019). The 3Rs and humane experimental technique: Implementing change. Animals 9, 754. doi:10.3390/ani9100754
Kleensang, A., Vantangoli, M. M., Odwin-DaCosta, S. et al. (2016). Genetic variability in a frozen batch of MCF-7 cells invisible in routine authentication affecting cell function. Sci Rep 6, 28994. doi:10.1038/srep28994
Luechtefeld, T., Maertens, A., Russo, D. P. et al. (2016a). Global analysis of publicly available safety data for 9,801 substances registered under REACH from 2008-2014. ALTEX 33, 95-109. doi:10.14573/altex.1510052
Luechtefeld, T., Maertens, A., Russo, D. P. et al. (2016b). Analysis of Draize eye irritation testing and its prediction by mining publicly available 2008-2014 REACH data. ALTEX 33, 123-134. doi:10.14573/altex.1510053
Luechtefeld, T., Marsh, D., Rowlands, C. et al. (2018). Machine learning of toxicological big data enables read-across structure activity relationships (RASAR) outperforming animal test reproducibility. Toxicol Sci 165, 198-212. doi:10.1093/toxsci/kfy152
Mansouri, K., Karmaus, A. L., Fitzpatrick, J. et al. (2021). CATMoS: Collaborative acute toxicity modeling suite. Environ Health Perspect 129, 47013. doi:10.1289/EHP8495
Meigs, L., Smirnova, L., Rovida, C. et al. (2018). Animal testing and its alternatives – The most important omics is economics. ALTEX 35, 275-305. doi:10.14573/altex.1807041
NRC – National Research Council (1977). Future of Animals, Cells, Models, and Systems in Research, Development, Education, and Testing: Proceedings of a Symposium. Washington, DC, USA: The National Academies Press. doi:10.17226/19908
NRC (2007). Toxicity Testing in the 21st Century: A Vision and a Strategy. Washington, DC, USA: The National Academies Press. doi:10.17226/11970
Pamies, D., Barreras, P., Block, K. et al. (2017). A human brain microphysiological system derived from induced pluripotent stem cells to study neurological diseases and toxicity. ALTEX 34, 362-376. doi:10.14573/altex.1609122
Pamies, D., Block, K., Lau, P. et al. (2018). Rotenone exerts developmental neurotoxicity in a human brain spheroid model. Toxicol Appl Pharmacol 354, 101-114. doi:10.1016/j.taap.2018.02.003
Pamies, D., Leist, M., Coecke, S. et al. (2022). Guidance document on good cell and tissue culture practice 2.0 (GCCP 2.0). ALTEX 39, 30-70. doi:10.14573/altex.2111011
Russell, W. M. S. and Burch R. L. (1959). The Principles of Humane Experimental Technique. London, UK: Methuen.
Russell, W. M. S. and Burch R. L. (1992). The Principles of Humane Experimental Technique. Potters Bar, Herts., UK: UFAW. https://caat.jhsph.edu/the-principles-of-humane-experimental-technique/
Russell, W. M. S. (1995). The W. M. S. Russell speech at the award luncheon. The World Congress on Alternatives and Animal Use in the Life Sciences: Education, Research, Testing (71-80). New York, USA: Mary Ann Liebert Publishing.
Stephens, M. L., Goldberg, A. M. and Rowan, A. N. (2001). The first forty years of the alternatives approach: Refining, reducing, and replacing the use of laboratory animals. In D. J. Salem and A. N. Rowan (eds), The State of the Animals (121-135). Washington, DC, USA: Humane Society Press. https://www.wellbeingintlstudiesrepository.org/cgi/viewcontent.cgi?article=1007&context=sota_2001
Stephens, M. L. (2009). Personal reflections on Russell and Burch, FRAME, and the HSUS. Altern Lab Anim 37, Suppl, 29-33. doi:10.1177/026119290903702s21
Tannenbaum, J. and Bennett, B. T. (2015). Russell and Burch’s 3Rs then and now: The need for clarity in definition and purpose. J Am Assoc Lab Anim Sci 54, 120-132.
Weil, C. S. and Scala, R. A. (1971). Study of intra- and interlaboratory variability in the results of rabbit eye and skin irritation tests. Toxicol Appl Pharmacol 192, 276-360. doi:10.1016/0041-008x(71)90112-8
Zbinden, G. and Flury-Roversi, M. (1981). Significance of the LD50-test for the toxicological evaluation of chemical substances. Arch Toxicol 47, 77-99. doi:10.1007/BF00332351
Zhong, X., Harris, G., Smirnova, L. et al. (2020). Antidepressant paroxetine exerts developmental neurotoxicity in an iPSC-derived 3D human brain model. Front Cell Neurosci 14, 25. doi:10.3389/fncel.2020.00025