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Animal Experiments in Biomedical Research: A Historical Perspective
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The use of non-human animals in biomedical research has given important contributions to the medical progress achieved in our day, but it has also been a cause of heated public, scientific and philosophical discussion for hundreds of years. This review, with a mainly European outlook, addresses the history of animal use in biomedical research, some of its main protagonists and antagonists, and its effect on society from Antiquity to the present day, while providing a historical context with which to understand how we have arrived at the current paradigm regarding the ethical treatment of animals in research.
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![Figure 3 “A physiological demonstration with vivisection of a dog,” by Émile-Édouard Mouchy. This 1832 oil painting—the only secular painting known of the artist—illustrates how French scholars valued physiological experimentation in service of scientific progress [90]. Notice how the struggling of the animal does not seem to affect the physiologist or his observers. Currently part of the Wellcome Gallery collection, London. Source: Wellcome Library.](/paper-figures/360d64dafc4e4af5ba4a4c6ff21ae13b/animal-experiments-in-biomedical-research-a-historical-perspective-figure-3.jpg)
![Figure 4 This full-page illustration of Pasteur in his animal facility was published in Harper’s Weekly in the United States, on 21 June 1884. At this time, there was moderate curiosity on Pasteur’s work in the US, which would intensify after his first successful human trials of a therapeutic vaccine for rabies in 1885. In the article, the reader is reassured that the use of dogs is both humane and justified in the interest of mankind. The use of other species, however, is barely mentioned [5]. Source: Images from the History of Medicine, U.S. National Library of Science.](/paper-figures/c8e8762450a241419dc2de63a748c4c1/animal-experiments-in-biomedical-research-a-historical-perspective-figure-4.jpg)
![Figure 5 Two outbred laboratory rats, of the Lister Hooded (Long–Evans) strain. Rodents are the most commonly used laboratory animals, making up nearly 80% of the total of animals used in the European Union, followed by cold-blooded animals (fish, amphibian and reptiles, making up a total of 9.6%) and birds (6.3%) [159] Photo: Francis Brosseron, reproduced with permission.](/paper-figures/2ea73cca9d2e4297968b76365a450a41/animal-experiments-in-biomedical-research-a-historical-perspective-figure-5.jpg)

![Figure 7 This schematic illustration (adapted with permission from an original by Professor Bert van Zupthen) attempts to describe trends in the use of animals for scientific purposes in the Western world across time. It depicts the emergence of the first vivisection studies by classical Greek physicians, the absence of animal-based research—along with most medical and scientific research—across the Middle Ages, its resurgence in the Renaissance onwards, and the rapid increase in animal studies following the rise of science-based physiology and medicine in the nineteenth century. The curves represented are nevertheless conjectural, as there are no reliable statistics on animal use for most of the period covered. Even nowadays it is hard to estimate trends in animal research, as data from several developed countries is insufficient (for instance, in the United States, rodents, fish and birds are not accounted for in the statistics). The available data, however, suggest that the number of animals used in research and testing in the Western world peaked in the 1970s, and decreased until the late 1990s, or early 2000s, to about half the number of 30 years earlier, and stabilizing in recent years. While many, if not most, researchers do not foresee an end to animal experiments in biomedicine, the European Commission has nevertheless set full replacement of animal experiments as an ultimate goal [204], and the Humane Society of the United States has the optimistic goal of full replacement by the year 2050 [192].](/paper-figures/b4ad8cda79fb4191b759a8c4d73c9626/animal-experiments-in-biomedical-research-a-historical-perspective-figure-7.jpg)
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Clutton, R. E. (2020) · Animals · doi:10.3390/ani10101933 · Cited by 17
“Additional dates for reference: [1]: 1873 Sanderson publishes, “Handbook for the Physiological Laboratory”; [2]: the Magnan “affair”; [3]: the brown dog affair.”
BackgroundBudharaju, H., Singh, R. K., & Kim, H. (2025) · Bioactive Materials · doi:10.1016/j.bioactmat.2025.07.006 · Cited by 15
Kahrass, H., Pietschmann, I., & Mertz, M. (2024) · Animals · doi:10.3390/ani14040651 · Cited by 12
“Interestingly, such reasons tend to be addressed more in the public/societal debate (e.g., [9]), both in the defense of animal experiments (here mainly those that refer to the scientific context) and in the criticism of them (here rather, although by no means exclusively, those that refer to the…”
BackgroundEthical Principles and Rules in Experimental Animal Studies: A Comprehensive Review
Kalkan, K. K., & Kekeçoğlu, M. (2024) · Düzce Tıp Fakültesi Dergisi · doi:10.18678/dtfd.1497730 · Cited by 13
12. Killing animals as a necessary evil? The case of animal research
Franco, N. H., & Olsson, I. A. S. (2016) · Wageningen Academic Publishers eBooks · doi:10.3920/978-90-8686-808-7_12 · Cited by 13
“The Judaeo-Christian religious moral tradition held that while one must abstain from cruelty, killing animals was not in itself morally problematic, as animals lacked an ‘immortal soul’ [42].”
BackgroundSelf-citationIf A.I. Only Had a Heart: Why Artificial Intelligence Research Needs to Take Emotions More Seriously
Merriam, G. (2021) · Journal of Artificial Intelligence and Consciousness · doi:10.1142/s2705078521500120 · Cited by 13
Education in laboratory animal science and the 3Rs
Franco, N. H., Kerton, A., & Lewis, D. I. (2023) · Laboratory Animals · doi:10.1177/00236772231162166 · Cited by 13
Self-citationÜlger, Ö., Eş, İ., Proctor, C. M., & Algın, O. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102469 · Cited by 12
Animal research, ethical boundary‐work, and the geographies of veterinary expertise
Anderson, A., & Hobson‐West, P. (2022) · Transactions of the Institute of British Geographers · doi:10.1111/tran.12594 · Cited by 12
“Using non-human animals as stand-ins for human bodies in research has a long history, and history of contestation (Franco, 2013).”
BackgroundKwak, J., Pandey, S., Cho, J. H., Song, M., Kim, E. S., Doo, H., Keum, G. B., Ryu, S., Choi, Y., Kang, J., et al. (2023) · Frontiers in Veterinary Science · doi:10.3389/fvets.2023.1226859 · Cited by 10
“Animal models are an important tool in biomedical research that allows scientists to study human diseases in a controlled environment, test potential treatments, and gain insights into how diseases work (24).”
Backgroundvan der Staay, F. J., Nordquist, R. E., & Arndt, S. S. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-809468-6.00003-6 · Cited by 10
“Animal model approaches have a long history in biomedical (Ericsson et al., 2013; Franco, 2013) and neuroscience research (cowan et al., 2000), where the models have been developed to investigate brain–behavior relations. the aim has been to gain insight into human behavior and its underlying…”
Liu, H., Gielen, M. J. C. A. M., Bosmans, J. W. A. M., Winkens, B., & Bouvy, N. D. (2021) · Hernia · doi:10.1007/s10029-020-02351-y · Cited by 11
Roy, R., Liya, I. J., Roy, J., & Basher, M. A. (2023) · Toxicology Reports · doi:10.1016/j.toxrep.2023.02.006 · Cited by 10
“Several behavioral parameters have been observed in this study that reveals the toxicity level of the plant extract is tolerable [30,31].”
BackgroundMugrabi-Oliveira, E., & Goldim, J. R. (2014) · Revista Bioética · doi:10.1590/s1983-80422014000100006 · Cited by 10
Mösch, L., Kunczik, J., Breuer, L., Merhof, D., Gass, P., Potschka, H., Zechner, D., Vollmar, B., Tolba, R. H., Häger, C., et al. (2023) · PLoS ONE · doi:10.1371/journal.pone.0286230 · Cited by 9
Mittal, R., Ho, A., Adivikolanu, H., Sawhney, M., Lemos, J. R. N., Mittal, M., & Hirani, K. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1644907 · Cited by 9
“…models has long been integral to drug testing and biomedical research, providing a foundation for understanding disease mechanisms, evaluating therapeutic ef fi cacy, and ensuring safety before clinical trial (Kinter et al., 2021; Domínguez-Oliva et al., 2023; Franco, 2013; Fernandes et al., 2025).”
Hankenson, F. C., Prager, E. M., & Berridge, B. R. (2024) · Annual Review of Animal Biosciences · doi:10.1146/annurev-animal-021022-043531 · Cited by 10
Penniston, K. L., Patel, S. R., Schwahn, D. J., & Nakada, S. Y. (2016) · Urolithiasis · doi:10.1007/s00240-016-0947-9 · Cited by 9
“Rats and mice were used in nutrition experiments in Europe prior to 1850 [5].”
MethodMany Cells Make Life Work—Multicellularity in Stem Cell-Based Cardiac Disease Modelling
Wang, B., Kit‐Anan, W., & Terracciano, C. M. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113361 · Cited by 13
Camera-Based Respiration Monitoring of Unconstrained Rodents
Breuer, L., Mösch, L., Kunczik, J., Buchecker, V., Potschka, H., Czaplik, M., & Pereira, C. B. (2023) · Animals · doi:10.3390/ani13121901 · Cited by 8
“Introduction Animal research has played a major role in many scientific breakthroughs for centuries, even though it has been a source of various ethical debates [1].”
BackgroundSafety and Toxicity Evaluation of Nutraceuticals in Animal Models
Goncharov, N. V., Sobolev, V. E., Terpilowski, M. A., Korf, E. A., & Jenkins, R. O. (2019) · Springer eBooks · doi:10.1007/978-3-030-04624-8_48 · Cited by 8
The Road Not Mapped: The Neuroethics Roadmap on Research with Nonhuman Primates
Johnson, L. S. M. (2020) · AJOB Neuroscience · doi:10.1080/21507740.2020.1778115 · Cited by 8
“His illegal, sacrilegious dissection of human cadavers led to more accurate descriptions of human anatomy, and also laid the foundations for modern comparative anatomy (Franco 2013).”
BackgroundНиколаевич, Л. К., Рыжков, И. А., Maltseva, V. A., & Удут, Е. В. (2021) · Bulletin of Siberian Medicine · doi:10.20538/1682-0363-2021-3-168-181 · Cited by 8
The Emperor’s New Clothes—An Epistemological Critique of Traditional Chinese Veterinary Acupuncture
Magalhães‐Sant’Ana, M. (2019) · Animals · doi:10.3390/ani9040168 · Cited by 10
“pathology during the second half of the nineteenth century, and thus casting the medical tradition based upon the authority of Hippocrates, Aristotle and Galen aside [16].”
BackgroundBusia, K. A. (2024) · Journal of Herbal Medicine · doi:10.1016/j.hermed.2024.100903 · Cited by 7
Chemicals regulation and non-animal methods: displacing the gold standard
Carusi, A. (2024) · Wellcome Open Research · doi:10.12688/wellcomeopenres.20581.2 · Cited by 7
Martins, A., & Franco, N. H. (2015) · Animals · doi:10.3390/ani5020315 · Cited by 7
“Animal experimentation has, for centuries, not only been a cornerstone of scientifically-based biomedical research, but also the subject of heated academic and public debate [1].”
BackgroundSelf-citationEthical Issues Associated with the Use of Animal Experimentation in Behavioral Neuroscience Research
Ohl, F., & Meijboom, F. L. B. (2014) · Current topics in behavioral neurosciences · doi:10.1007/7854_2014_328 · Cited by 7
“While perhaps earliest concerns about experimentation involving live animals arose in the UK in the nineteenth century (Franco 2013), debate about the moral status of animals is not restricted to Europe, but is nowadays of concern in many countries including the US, Australia and Asian countries…”
Introduction to “Working Across Species”
Dentinger, R. M., & Woods, A. (2018) · History & Philosophy of the Life Sciences · doi:10.1007/s40656-018-0197-y · Cited by 7
“2 For mazes: Kirk and Ramsden (2018); For tanks: Hagen (2018).”
BackgroundNon-genetic rats models for atherosclerosis research from past to present
Gasparotto, A. (2019) · Frontiers in Bioscience-Scholar · doi:10.2741/s535 · Cited by 7
“They are responsible for the most evident advances in many biological fields to prevent, diagnose, and treat diseases (24, 35-38).”
BackgroundGaganis, V., Beckett, E. A. H., Choate, J., Aguilar-Roca, N. M., Etherington, S. J., Haigh, C., Scott, D. A., Sweeney, T., Zubek, J., & French, M. B. (2021) · AJP Advances in Physiology Education · doi:10.1152/advan.00242.2020 · Cited by 7
Paździor‐Czapula, K., Mikiewicz, M., Fiedorowicz, J., & Otrocka‐Domagała, I. (2024) · Journal of Comparative Pathology · doi:10.1016/j.jcpa.2024.07.002 · Cited by 6
Use of artificial intelligence in animal experimentation: A review
Gonçalves, S. D., Rodrigues, M., Avidos, M., Morais, A. B., & Caramelo, A. (2025) · Toxicology Letters · doi:10.1016/j.toxlet.2025.07.1417 · Cited by 8
Greek, R., & Kramer, L. A. (2019) · BRILL eBooks · doi:10.1163/9789004391192_003 · Cited by 6
“Formal objections to the practice emerged as early as the seventeenth century, primar ily based on moral objections (Franco, 2013).”
Sardjono, T. W., Gondo, H. K., Nugraha, R. Y. B., Putri, A. T., & Effendy, M. C. O. S. (2019) · Journal of Tropical Life Science · doi:10.11594/jtls.09.03.03 · Cited by 6
The 3Rs in Experimental Liver Disease
Martínez‐López, S., Ángel‐Gomis, E., Sánchez, E., Pastor-Campos, A., Picó, J., & Gómez‐Hurtado, I. (2023) · Animals · doi:10.3390/ani13142357 · Cited by 9
“One of the principal reasons for their use is that animals and humans have many anatomical and biological similarities [7].”
BackgroundMethodological and Ethical Considerations in the Use of Chordate Embryos in Biomedical Research
Campitelli, L. M. M., Lopes, K. P., de Lima, I. L., Ferreira, F. B., Isidoro, N. D., Ferreira, G. M., Ponce, M. C. F., Ferreira, M. C. D. O., Mendes, L. S., Marcelino, P. H. R., et al. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26062624 · Cited by 5
“…to meet other requirements, such as minimizing the number of animals to the greatest extent possible, refining the study as much as possible to cause the least harm and stress to the animals, and replacing animal testing with alternative methods like in vitro experiments whenever possible [2,4,5].”
Alternatives to animal models to study bacterial infections
Hu, C., & Yang, W. (2023) · Folia Microbiologica · doi:10.1007/s12223-023-01084-6 · Cited by 5
“The use of animals in testing has been a subject of ongoing debate due to concerns about the pain, suffering, and death of animals used in research (Festing and Wilkinson 2007; Franco 2013).”
BackgroundDiscussing the use of animal models in biomedical research via role play simulation
Siani, A. (2018) · International Journal of Ethics Education · doi:10.1007/s40889-018-0064-4 · Cited by 5
“The structural and functional similarities between the human body and that of other vertebrates were well acknowledged by physicians in ancient Greece, where the practice of vivisection and dissection of animals (and, notably, convicted criminals) were commonplace in medical science (Franco 2013).”
BackgroundA Philosophical Approach to Animal Rights and Welfare in the Tourism Sector
Küçükaltan, E. G., & Dilek, S. E. (2019) · DergiPark (Istanbul University) · Cited by 5
Harry Harlow's pit of despair: Depression in monkeys and men
van Rosmalen, L., Luijk, M. P. C. M., & van der Horst, F. C. P. (2022) · Journal of the History of the Behavioral Sciences · doi:10.1002/jhbs.22180 · Cited by 7
Pace, L. D., Viviani, L., & Straccia, M. (2022) · Animals · doi:10.3390/ani12202778 · Cited by 5
Significance of animal experimentation in biomedical research in the current era: Narrative review
Sakat, S. S., Bagade, O. M., Mhaske, G. R., Taru, P., Sagar, M., & Rastogi, M. (2022) · Journal of Applied Pharmaceutical Science · doi:10.7324/japs.2022.121002-1 · Cited by 5
“However, a lack of knowledge usually rendered a majority of such observations error-prone, thus leading to the ultimate demise of such practices in the later centuries (Franco, 2013, Maehle and Trohler, 1987).”
BackgroundAlstrup, A. K. O., Jensen, S. B., Nielsen, O. L., Jødal, L., & Afzelius, P. (2021) · Molecules · doi:10.3390/molecules26144221 · Cited by 4
“Animal experiments are required to bridge the gap between laboratory inventions and the clinic [5].”
BackgroundHuang, X., Nussler, A. K., Reumann, M. K., Augat, P., Menger, M. M., Ghallab, A., Hengstler, J. G., Histing, T., & Ehnert, S. (2022) · Bioengineering · doi:10.3390/bioengineering9080337 · Cited by 4
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Microsatellite Marker Analysis for Laboratory Mice Profiling
Farhoudi, R., Cohan, R. A., Inanlou, D. N., Aref, M. H. S., & Zeinali, S. (2019) · Advanced Biomedical Research · doi:10.4103/abr.abr_53_19 · Cited by 4
Zavitz, T., & Kielbiski, C. (2021) · Networking Knowledge Journal of the MeCCSA Postgraduate Network · doi:10.31165/nk.2021.142.643 · Cited by 4
“In contrast to the strict non-anthropomorphisation of animals that is an unwritten rule of science (Franco 2013), Fowler displays Fern with a complex subjectivity.”
BackgroundEmpirical evidence of animals used in biomedical research in unani medicine: An appraisal
Ansari, A. P., Ahmed, N. Z., & Dar, P. (2018) · International Journal of Unani and Integrative Medicine · doi:10.33545/2616454x.2018.v2.i4a.56 · Cited by 4
Koterov, A. N. (2022) · Biology Bulletin · doi:10.1134/s1062359022110115 · Cited by 4
Mann, M. K. (2017) · ACS symposium series · doi:10.1021/bk-2017-1266.ch004 · Cited by 4
Metadata
- Authors
- Franco, N.
- Affiliations
- Universidade do Porto (PT)
- Corresponding author
- Franco, Nuno
- ORCID
- Franco, Nuno
- Venue
- Animals
- Publisher
- MDPI AG
- Published
- 2013-03-19
- Volume
- 3
- Issue
- 1
- Pages
- 238-273
- ISSN
- 2076-2615 (ISSN-L)
- PMC
- PMC4495509
- OpenAlex
- W2124183503
- Cited by
- 265
- References
- 165
- Citations by year
- 2026: 21 · 2025: 31 · 2024: 31 · 2023: 24 · 2022: 30 · 2021: 24 · 2020: 27 · 2019: 24 · 2018: 15 · 2017: 13 · 2016: 6 · 2015: 6 · 2014: 7 · 2013: 3
- FWCI
- 1.70
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Animals (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
- Social Sciences › Law › Animal Law and Welfare
- Social Sciences › Arts and Humanities › History and Philosophy of Science › History of Science and Medicine
- Keywords
- animal experimentation, history of animal research, biomedical research, animal ethics, animal welfare, European history
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