The flaws and human harms of animal experimentation.
paper
Cited
Public
- Authors
- Akhtar, Aysha
- Year
- 2015
- Journal
- Cambridge quarterly of healthcare ethics : CQ : the international journal of healthcare ethics committees
- PMID
- 26364776
- DOI
- 10.1017/S0963180115000079
- PMCID
- PMC4594046
Nonhuman animal ("animal") experimentation is typically defended by arguments that it is reliable, that animals provide sufficiently good models of human biology and diseases to yield relevant information, and that, consequently, its use provides major human health benefits. I demonstrate that a growing body of scientific literature critically assessing the validity of animal experimentation generally (and animal modeling specifically) raises important concerns about its reliability and predictive value for human outcomes and for understanding human physiology. The unreliability of animal experimentation across a wide range of areas undermines scientific arguments in favor of the practice. Additionally, I show how animal experimentation often significantly harms humans through misleading safety studies, potential abandonment of effective therapeutics, and direction of resources away from more effective testing methods. The resulting evidence suggests that the collective harms and costs to humans from animal experimentation outweigh potential benefits and that resources would be better invested in developing human-based testing methods.
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| # | Section | Preview |
|---|---|---|
| 0 | Introduction | Annually, more than 115 million animals are used worldwide in experimentation or to supply the⦠|
| 1 | Introduction | Although it is widely accepted that medicine should be evidence based, animal experimentation as a⦠|
| 2 | Problems of Successful Translation to Humans of Data from Animal Experimentation | Although the unreliability and limitations of animal experimentation have increasingly been⦠|
| 3 | Problems of Successful Translation to Humans of Data from Animal Experimentation β The Influence of Laboratory Procedures and Environments on Experimental Results | Laboratory procedures and conditions exert influences on animalsβ physiology and behaviors thatβ¦ |
| 4 | Problems of Successful Translation to Humans of Data from Animal Experimentation β The Influence of Laboratory Procedures and Environments on Experimental Results | A variety of conditions in the laboratory cause changes in neurochemistry, genetic expression, andβ¦ |
| 5 | Problems of Successful Translation to Humans of Data from Animal Experimentation β The Influence of Laboratory Procedures and Environments on Experimental Results | In order to control for potential confounders, some investigators have called for standardization ofβ¦ |
| 6 | Problems of Successful Translation to Humans of Data from Animal Experimentation β The Discordance between Human Diseases and Animal Models of Diseases | The lack of sufficient congruence between animal models and human diseases is another significantβ¦ |
| 7 | Problems of Successful Translation to Humans of Data from Animal Experimentation β The Discordance between Human Diseases and Animal Models of Diseases | Stroke research presents one salient example of the difficulties in modeling human diseases inβ¦ |
| 8 | Problems of Successful Translation to Humans of Data from Animal Experimentation β The Discordance between Human Diseases and Animal Models of Diseases | treatments later to emerge was NXY-059, which proved effective in animal experiments. However, theβ¦ |
| 9 | Problems of Successful Translation to Humans of Data from Animal Experimentation β The Discordance between Human Diseases and Animal Models of Diseases | Under closer scrutiny, it is not difficult to surmise why animal stroke experiments fail toβ¦ |
| 10 | Problems of Successful Translation to Humans of Data from Animal Experimentation β The Discordance between Human Diseases and Animal Models of Diseases | Further examples of repeated failures based on animal models include drug development in cancer,β¦ |
| 11 | Problems of Successful Translation to Humans of Data from Animal Experimentation β The Discordance between Human Diseases and Animal Models of Diseases | and Drug Administration (FDA)βapproved drug to treat ALS is Riluzole, which shows notably marginalβ¦ |
| 12 | Problems of Successful Translation to Humans of Data from Animal Experimentation β The Discordance between Human Diseases and Animal Models of Diseases | The high clinical failure rate in drug development across all disease categories is based, at leastβ¦ |
| 13 | Problems of Successful Translation to Humans of Data from Animal Experimentation β The Discordance between Human Diseases and Animal Models of Diseases | In 2004, the FDA estimated that 92 percent of drugs that pass preclinical tests, includingβ¦ |
| 14 | Problems of Successful Translation to Humans of Data from Animal Experimentation β The Discordance between Human Diseases and Animal Models of Diseases | Usually, when an animal model is found wanting, various reasons are proffered to explain what wentβ¦ |
| 15 | Problems of Successful Translation to Humans of Data from Animal Experimentation β Interspecies Differences in Physiology and Genetics | Ultimately, even if considerable congruence were shown between an animal model and its correspondingβ¦ |
| 16 | Problems of Successful Translation to Humans of Data from Animal Experimentation β Interspecies Differences in Physiology and Genetics | Even rats from the same strain but purchased from different suppliers produce different testβ¦ |
| 17 | Problems of Successful Translation to Humans of Data from Animal Experimentation β Interspecies Differences in Physiology and Genetics | Further exemplifying the importance of physiological differences among species, a 2013 studyβ¦ |
| 18 | Problems of Successful Translation to Humans of Data from Animal Experimentation β Interspecies Differences in Physiology and Genetics | Wide differences have also become apparent in the regulation of the same genes, a point that isβ¦ |
| 19 | Problems of Successful Translation to Humans of Data from Animal Experimentation β Interspecies Differences in Physiology and Genetics | Recognizing the inherent genetic differences among species as a barrier to translation, researchesβ¦ |
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| Modeling Developmental Brain Diseases Using Human Pluripotent Stem Cells-Derived Brain Organoids - Progress and Perspective. | Bhattacharya A et al. | β | 2022 | β |
| Model systems and organisms for addressing inter- and intra-species variability in risk assessment. | Rusyn I et al. | β | 2022 | β |
| Numerical and experimental evaluation of ultrasound-assisted convection enhanced delivery to transfer drugs into brain tumors. | Boroumand A et al. | β | 2022 | β |
| Organoid factory: The recent role of the human induced pluripotent stem cells (hiPSCs) in precision medicine. | Novelli G et al. | β | 2022 | β |
| Organ-specific endothelial cell heterogenicity and its impact on regenerative medicine and biomedical engineering applications. | Urbanczyk M et al. | β | 2022 | β |
| Protecting Canada's Lab Animals: The Need for Legislation. | Black V et al. | β | 2022 | β |
| Rapid Detection of Direct Compound Toxicity and Trailing Detection of Indirect Cell Metabolite Toxicity in a 96-Well Fluidic Culture Device for Cell-Based Screening Environments: Tactics in Six Sigma Quality Control Charts. | Lubamba B et al. | β | 2022 | β |
| Small tissue chips with big opportunities for space medicine. | Mu X et al. | β | 2022 | β |
| Targeting of colorectal cancer organoids with zoledronic acid conjugated to the anti-EGFR antibody cetuximab. | Benelli R et al. | β | 2022 | β |
| Threats to Benefits: Assessing Knowledge Production in Nonhuman Models of Human Neuropsychiatric Disorders. | Neuhaus CP | β | 2022 | β |
| Three-dimensional (3D) liver cell models - a tool for bridging the gap between animal studies and clinical trials when screening liver accumulation and toxicity of nanobiomaterials. | Tutty MA et al. | β | 2022 | β |
| To Affinity and Beyond: A Personal Reflection on the Design and Discovery of Drugs. | Flower DR | β | 2022 | β |
| A Facile and Scalable Hydrogel Patterning Method for Microfluidic 3D Cell Culture and Spheroid-in-Gel Culture Array. | Su C et al. | β | 2021 | β |
| An overview of in vitro, ex vivo and in vivo models for studying the transport of drugs across intestinal barriers. | Xu Y et al. | β | 2021 | β |
| Biomimetics provides lessons from nature for contemporary ways to improve human health. | Stenvinkel P et al. | β | 2021 | β |
| ChemBioSim: Enhancing Conformal Prediction of In Vivo Toxicity by Use of Predicted Bioactivities. | Garcia de Lomana M et al. | β | 2021 | β |
| Current advances of stem cell-based therapy for kidney diseases. | Wong CY | β | 2021 | β |
| Devices and techniques used to obtain and analyze three-dimensional cell cultures. | Agrawal G et al. | β | 2021 | β |
| Effects of Laboratory Housing Conditions on Core Temperature and Locomotor Activity in Mice. | Russell LN et al. | β | 2021 | β |
| Evaluation of the global performance of eight in silico skin sensitization models using human data. | Golden E et al. | β | 2021 | β |
| Exploring the Gamut of Receptor Tyrosine Kinases for Their Promise in the Management of Non-Alcoholic Fatty Liver Disease. | Bhave S et al. | β | 2021 | β |
| Human lung-on-chips: Advanced systems for respiratory virus models and assessment of immune response. | Saygili E et al. | β | 2021 | β |
| Hydrogels in the treatment of rheumatoid arthritis: drug delivery systems and artificial matrices for dynamic in vitro models. | Oliveira IM et al. | β | 2021 | β |
| <i>In vitro</i> Modeling of Chicken Cecal Microbiota Ecology and Metabolism Using the PolyFermS Platform. | Asare PT et al. | β | 2021 | β |
| It's Time to Include Harm to Humans in Harm-Benefit Analysis - But How to Do It, That is the Question. | Balls M | β | 2021 | β |
| Liver-spleen axis in nonalcoholic fatty liver disease. | Tarantino G et al. | β | 2021 | β |
| <sup>1</sup>H Nuclear Magnetic Resonance: A Future Approach to the Metabolic Profiling of Psychedelics in Human Biofluids? | Vilca-Melendez S et al. | β | 2021 | β |
| Material Risks of Homeopathic Medicinal Products: Regulatory Frameworks, Results of Preclinical Toxicology, and Clinical Meta-Analyses and Their Implications. | Habs M et al. | β | 2021 | β |
| Organ-on-a-chip platforms for accelerating the evaluation of nanomedicine. | Chen X et al. | β | 2021 | β |
| Reversed-engineered human alveolar lung-on-a-chip model. | Huang D et al. | β | 2021 | β |
| The laboratory rat: Age and body weight matter. | Ghasemi A et al. | β | 2021 | β |
| Tissue-specific parameters for the design of ECM-mimetic biomaterials. | Tonti OR et al. | β | 2021 | β |
| Toxicity of Combinations of Kinase Pathway Inhibitors to Normal Human Cells in a Three-Dimensional Culture. | Rafsanjani Nejad P et al. | β | 2021 | β |
| Translational precision medicine: an industry perspective. | Hartl D et al. | β | 2021 | β |
| What's not in the news headlines or titles of Alzheimer disease articles? #InMice. | Triunfol M et al. | β | 2021 | β |
| Zebrafish: A Promising Real-Time Model System for Nanotechnology-Mediated Neurospecific Drug Delivery. | Saleem S et al. | β | 2021 | β |
| 3D Cell Printing of Tissue/Organ-Mimicking Constructs for Therapeutic and Drug Testing Applications. | Kim J et al. | β | 2020 | β |
| Accepting higher morbidity in exchange for sacrificing fewer animals in studies developing novel infection-control strategies. | Busscher HJ et al. | β | 2020 | β |
| Are the Lives of Animals Well-spent in Laboratory Science Research? A Study of Orthopaedic Animal Studies in Turkey. | ΓztΓΌrk A et al. | β | 2020 | β |
| Biomaterials and Culture Systems for Development of Organoid and Organ-on-a-Chip Models. | D'Costa K et al. | β | 2020 | β |
| Decellularized tissues as platforms for in vitro modeling of healthy and diseased tissues. | McCrary MW et al. | β | 2020 | β |
| Dehydration Impairs Physical Growth and Cognitive Development in Young Mice. | Kim CS et al. | β | 2020 | β |
| Development of In Vitro Corneal Models: Opportunity for Pharmacological Testing. | Citi V et al. | β | 2020 | β |
| Driver versus navigator causation in biology: the case of insulin and fasting glucose. | Diwekar-Joshi M et al. | β | 2020 | β |
| Drug Discovery: Today and Tomorrow. | Flower DR | β | 2020 | β |
| Engineered Hydrogels for Brain Tumor Culture and Therapy. | Thakor J et al. | β | 2020 | β |
| Feasibility of fresh frozen human cadavers as a research and training model for endovascular image guided interventions. | Jansen MM et al. | β | 2020 | β |
| Importance of Systematic Reviews and Meta-analyses of Animal Studies: Challenges for Animal-to-Human Translation. | Bahadoran Z et al. | β | 2020 | β |
| Induced Pluripotency: A Powerful Tool for In Vitro Modeling. | Zahumenska R et al. | β | 2020 | β |
| Invited Commentary on "the translation of surgical animal models to human clinical research: A cross sectional study". | Raja SG | β | 2020 | β |
| Is it Time for Reviewer 3 to Request Human Organ Chip Experiments Instead of Animal Validation Studies? | Ingber DE | β | 2020 | β |
| Lung-on-a-chip: the future of respiratory disease models and pharmacological studies. | Shrestha J et al. | β | 2020 | β |
| Medical research during the COVID-19 pandemic. | AlNaamani K et al. | β | 2020 | β |
| Modeling alcohol-induced neurotoxicity using human induced pluripotent stem cell-derived three-dimensional cerebral organoids. | Arzua T et al. | β | 2020 | β |
| Organotypic Models to Study Human Glioblastoma: Studying the Beast in Its Ecosystem. | Pamies D et al. | β | 2020 | β |
| Physical Characterization of Colorectal Cancer Spheroids and Evaluation of NK Cell Infiltration Through a Flow-Based Analysis. | Sargenti A et al. | β | 2020 | β |
| Predictive Models for Human Organ Toxicity Based on <i>In Vitro</i> Bioactivity Data and Chemical Structure. | Xu T et al. | β | 2020 | β |
| Publication and Citation Analysis of Medical Doctors' Residency Master's Theses Involving Animal Experiments on Rats in Turkey. | KinikoΔlu O et al. | β | 2020 | β |
| QSAR Use in REACH Analyses of Alternatives to Predict Human Health and Environmental Toxicity of Alternative Chemical Substances. | Chinen K et al. | β | 2020 | β |
| Reevaluating Benefits in the Moral Justification of Animal Research: A Comment on "Necessary Conditions for Morally Responsible Animal Research". | Eggel M et al. | β | 2020 | β |
| The effects of Elaeagnus angustifolia L. whole fruit on the sex hormone profile in menopausal women: A double-blind, randomized, placebo-controlled study. | Emaminia F et al. | β | 2020 | β |
| The Implementation of the Three Rs in Regulatory Toxicity and Biosafety Assessment: The Indian Perspective. | Pant AB | β | 2020 | β |
| The (in)adequacy of translational research in dentistry. | Faggion CM | β | 2020 | β |
| Toxicity testing is evolving! | Fischer I et al. | β | 2020 | β |
| 3D Printing Breast Tissue Models: A Review of Past Work and Directions for Future Work. | Cleversey C et al. | β | 2019 | β |
| A Human iPSC-derived 3D platform using primary brain cancer cells to study drug development and personalized medicine. | Plummer S et al. | β | 2019 | β |
| A human proximal tubule-on-a-chip to study renal disease and toxicity. | Sakolish CM et al. | β | 2019 | β |
| An Estimate of the Number of Animals Used for Scientific Purposes Worldwide in 2015. | Taylor K et al. | β | 2019 | β |
| Animal Models and Animal Experimentation in the Development of Deep Brain Stimulation: From a Specific Controversy to a Multidimensional Debate. | Desmoulin-Canselier S et al. | β | 2019 | β |
| An in vitro chicken gut model for the assessment of phytase producing bacteria. | Priyodip P et al. | β | 2019 | β |
| Commentary: Do not kill (especially for nothing). | Hameed I et al. | β | 2019 | β |
| HDAC6 Modulates Signaling Pathways Relevant to Synaptic Biology and Neuronal Differentiation in Human Stem-Cell-Derived Neurons. | Iaconelli J et al. | β | 2019 | β |
| Humanized Mouse Models of Rheumatoid Arthritis for Studies on Immunopathogenesis and Preclinical Testing of Cell-Based Therapies. | Schinnerling K et al. | β | 2019 | β |
| Limitations of Animal Studies for Predicting Toxicity in Clinical Trials: Is it Time to Rethink Our Current Approach? | Van Norman GA | β | 2019 | β |
| Nanoformulated Zoledronic Acid Boosts the VΞ΄2 T Cell Immunotherapeutic Potential in Colorectal Cancer. | Di Mascolo D et al. | β | 2019 | β |
| Rapid maturation of the hepatic cell line Huh7 via CDK inhibition for PXR dependent CYP450 metabolism and induction. | Bulutoglu B et al. | β | 2019 | β |
| Recalcitrant Issues and New Frontiers in Nano-Pharmacology. | Bhardwaj V et al. | β | 2019 | β |
| Somatosensory predictors of response to pregabalin in painful chemotherapy-induced peripheral neuropathy: a randomized, placebo-controlled, crossover study. | Hincker A et al. | β | 2019 | β |
| Studying Human Neurological Disorders Using Induced Pluripotent Stem Cells: From 2D Monolayer to 3D Organoid and Blood Brain Barrier Models. | Logan S et al. | β | 2019 | β |
| The Power of LC-MS Based Multiomics: Exploring Adipogenic Differentiation of Human Mesenchymal Stem/Stromal Cells. | Rampler E et al. | β | 2019 | β |
| Thromboinflammation as bioactivity assessment of H<sub>2</sub>O<sub>2</sub>-alkali modified titanium surfaces. | Hulsart-BillstrΓΆm G et al. | β | 2019 | β |
| Time for a makeover-cosmetics regulation in the United States. | Cornell EM et al. | β | 2019 | β |
| Translatability of the S7A core battery respiratory safety pharmacology studies: Preclinical respiratory and related clinical adverse events. | Paglialunga S et al. | β | 2019 | β |
| Using human stem cells as a model system to understand the neural mechanisms of alcohol use disorders: Current status and outlook. | Scarnati MS et al. | β | 2019 | β |
| Validation and stability analysis of a modified lactate dehydrogenase (LDH) test method to be employed for an <i>in vitro</i> viable skin model. | Bauhammer I et al. | β | 2019 | β |
| AF710B, an M1/sigma-1 receptor agonist with long-lasting disease-modifying properties in a transgenic rat model of Alzheimer's disease. | Hall H et al. | β | 2018 | β |
| Directing neuronal cell fate in vitro: Achievements and challenges. | Riemens RJM et al. | β | 2018 | β |
| Effects of Rodent Thermoregulation on Animal Models in the Research Environment. | Hankenson FC et al. | β | 2018 | β |
| Machine Learning Based Toxicity Prediction: From Chemical Structural Description to Transcriptome Analysis. | Wu Y et al. | β | 2018 | β |
| Neuroprotective Effects of Human Mesenchymal Stem Cells and Platelet-Derived Growth Factor on Human Retinal Ganglion Cells. | Osborne A et al. | β | 2018 | β |
| Probing characteristics of cancer cells cultured on engineered platforms simulating different microenvironments. | Jo Y et al. | β | 2018 | β |
| Reduction of Animal Sacrifice in Biomedical Science & Research through Alternative Design of Animal Experiments. | Rai J et al. | β | 2018 | β |
| Study of melatonin-mediated effects on various hepatic inflammatory responses stimulated by IL-6 in a new HepG2-on-a-chip platform. | Jang M et al. | β | 2018 | β |
| The Human Vaccines Project: Towards a comprehensive understanding of the human immune response to immunization. | Wooden SL et al. | β | 2018 | β |
| Thrombosis-on-a-chip: Prospective impact of microphysiological models of vascular thrombosis. | Pandian NKR et al. | β | 2018 | β |
| Zoledronate Triggers VΞ΄2 T Cells to Destroy and Kill Spheroids of Colon Carcinoma: Quantitative Image Analysis of Three-Dimensional Cultures. | Varesano S et al. | β | 2018 | β |
| A Balanced Risk-Benefit Analysis to Determine Human Risks Associated with Pyrrolizidine Alkaloids (PA)-The Case of Tea and Herbal Infusions. | Habs M et al. | β | 2017 | β |
| Air Quality Effects on Human Health and Approaches for Its Assessment through Microfluidic Chips. | Schulze F et al. | β | 2017 | β |
| <i>IKBKAP/ELP1</i> gene mutations: mechanisms of familial dysautonomia and gene-targeting therapies. | Rubin BY et al. | β | 2017 | β |
| In vitro models as a platform to investigate traumatic brain injury. | Kumaria A | β | 2017 | β |
| Ionizing Radiation Alters Human Embryonic Stem Cell Properties and Differentiation Capacity by Diminishing the Expression of Activin Receptors. | Luft S et al. | β | 2017 | β |
| Linking acute kidney injury to chronic kidney disease: the missing links. | Kaballo MA et al. | β | 2017 | β |
| Nonhuman Animals, Public Health, and Ethics: A First Step, Butβ¦. | Akhtar A | β | 2017 | β |
| Postmarketing withdrawal of human medicinal products because of adverse reactions in animals: a systematic review and analysis. | Onakpoya IJ et al. | β | 2017 | β |
| The use of gatekeeping procedures in the statistical planning of animal experiments. | Mayer B et al. | β | 2017 | β |
| When Enough Is Enough: Decision Criteria for Moving a Known Drug into Clinical Testing for a New Indication in the Absence of Preclinical Efficacy Data. | Pulley JM et al. | β | 2017 | β |
| An Integrated Review of Psychological Stress in Parkinson's Disease: Biological Mechanisms and Symptom and Health Outcomes. | Austin KW et al. | β | 2016 | β |
| Apolipoprotein A5 fifteen years anniversary: Lessons from genetic epidemiology. | Hubacek JA | β | 2016 | β |
| Lung-On-A-Chip Technologies for Disease Modeling and Drug Development. | Konar D et al. | β | 2016 | β |
| Response to "Comment on 'Lessons from Toxicology: Developing a 21st-Century Paradigm for Medical Research'". | Langley G | β | 2016 | β |
| The ethics of animal research: a survey of the public and scientists in North America. | Joffe AR et al. | β | 2016 | β |
| The light switch-off response as a putative rodent test of innate fear. | Saito VM et al. | β | 2016 | β |
| True alignment of preclinical and clinical research to enhance success in CNS drug development: a review of the current evidence. | Goetghebeur PJ et al. | β | 2016 | β |
| Worldwide withdrawal of medicinal products because of adverse drug reactions: a systematic review and analysis. | Onakpoya IJ et al. | β | 2016 | β |
| Necessary conditions for morally responsible animal research. | DeGrazia D et al. | β | 2015 | β |
| The upper limits of pain and suffering in animal research. | Beauchamp TL et al. | β | 2015 | β |