Quotes by Scientific Articles

"Proponents of animal research claim that the benefits to humans are self evident. However, writing in The BMJ 10 years ago we argued that such uncorroborated claims were inadequate in an era of evidence based medicine. At that time over two thirds of UK government and charitable investment was going into basic research, perhaps creating an expectation that such research was highly productive of clinical benefits. However, when we searched for systematic evidence to support claims about the clinical benefits of animal research we identified only 25 systematic reviews of animal experiments, and these raised serious doubts about the design, quality, and relevance of the included studies."
[Dr Pound P,  dr. Bracken MB. Is animal research sufficiently evidence based to be a cornerstone of biomedical research? BMJ, May 2014, 30;348:g3387. doi: 10.1136/bmj.g3387.]

“If there was an animal model good enough to substitute for people, we would not have a 92% failure rate in clinical trials.”
[Dr. Thomas Hartung  quoted in Nature Medicine]
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“The chimpanzee is our closest living relative. The early genome comparison by DNA hybridization techniques suggested a nucleotide difference of 1-2%. However, if one looks at proteins, which are mainly responsible for phenotypic differences, the picture is quite different, and about 80% of proteins are different between the two species.”
[Dr. Glazko, Dr. Veeramachaneni, Dr. Nei, Dr. Makałowski. Eighty percent of proteins are different between humans and chimpanzees. Gene. 2005 Feb 14;346:215-9.]
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“Although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions”
[Dr. Seok et al. Genomic responses in mouse models poorly mimic human inflammatory diseases. PNAS 2013]
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“The low predictivity of animal experiments in research areas allowing direct comparisons of mouse versus human data puts strong doubt on the usefulness of animal data as key technology to predict human safety.”
[…] Can one show, or reasonably assume, that the predictivity of animals for man does not differ fundamentally in different fields of biomedical research? The answer from screening the scientific literature must be clearly ‘yes’.”
[Dr. Hartung & Dr. Leist. Inflammatory findings on species extrapolations: humans are definitely no 70-kg mice. Arch Toxicol. 2013 Apr;87(4):563-7.]
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“We conclude that even if legitimate criticisms of animal models were addressed, through standardization of protocols and systematic reviews, the animal model would still fail as a predictive modality for human response to drugs and disease.”
[Dr. Greek & Dr. Menache. Systematic Reviews of Animal Models: Methodology versus Epistemology. Int J Med Sci. 2013; 10(3): 206–221.]
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“Despite the lack of systematic evidence for its effectiveness, basic animal research in the United Kingdom receives much more funding than clinical research.”
[Dr. Pound, Dr. Ebrahim, Dr. Sandercock, Dr. Bracken, Dr. Roberts et al. Where is the evidence that animal research benefits humans? BMJ. 2004 February 28; 328(7438): 514–517.]
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“Changes from baseline or control measures typically ranged from 20% to 100% or more and lasted at least 30 min or longer. We interpret these findings to indicate that laboratory routines are associated with stress, and that animals do not readily habituate to them. The data suggest that significant fear, stress, and possibly distress are predictable consequences of routine laboratory procedures, and that these phenomena have substantial scientific and humane implications for the use of animals in laboratory research.”
[Dr. Balcombe, Dr. Barnard, Dr. Sandusky. Laboratory routines cause animal stress. Contemp Top Lab Anim Sci. 2004 Nov;43(6):42-51.]
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“We conclude that the use of sentient animals in basic research cannot be justified in light of society’s priorities.”
[Dr. R. Greek, Dr. J. Greek. Is the use of sentient animals in basic research justifiable? Philos Ethics Humanit Med. 2010 Sep 8;5:14. doi: 10.1186/1747-5341-5-14.]
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“Laboratory animal models are limited by scientific constraints on human applicability, and increasing regulatory restrictions, driven by social concerns. However, a range of non-animal methodologies is available within biomedical research and toxicity testing.”
[Dr. Knight. Non-animal methodologies within biomedical research and toxicity testing. ALTEX. 2008;25(3):213-31.]
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“The ability of animal studies to detect serious post marketing adverse events is limited.”
[Dr. van Meer, Dr. Kooijman, Dr. Gispen-de Wied, Dr. Moors, Dr. Schellekens. The ability of animal studies to detect serious post marketing adverse events is limited. Regul Toxicol Pharmacol. 2012 Dec;64(3):345-9.]
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“Replacing animal procedures with methods such as cells and tissues in vitro, volunteer studies, physicochemical techniques and computer modelling, is driven by legislative, scientific and moral imperatives. Non-animal approaches are now considered as advanced methods that can overcome many of the limitations of animal experiments.”
[Dr. Langley, Dr. Evans, Dr. Holgate, Dr. Jones. Replacing animal experiments: choices, chances and challenges. Bioessays 2007; 29(9): 918-26.]
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“Animal experiments scrutinised: systematic reviews demonstrate poor human clinical and toxicological utility.”
[Dr. Knight. ALTEX. 2007;24(4):320-5.]
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“The results of drug tests in mice have never translated perfectly to tests in humans. But in recent years, and especially for neurodegenerative diseases, mouse model results have seemed nearly useless.”
[Dr. Schnabel. Neuroscience: Standard model. Nature. 2008 Aug 7;454(7205):682-5.]
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“The toxicology tests on which regulators rely to gather this information are stuck in a time warp, and are largely based on wasteful and often poorly predictive animal experiments.”
[Dr. Abbott. Animal testing: more than a cosmetic change. Nature 2005 Nov 10;438(7065):144-146.]
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“There is a great deal of often overlooked data showing non-human primates research to be irrelevant, unnecessary, even hazardous to human health and to have little or no predictive value or application to human medicine.”
[Dr. Bailey. Non-human primates in medical research and drug development: a critical review. Biogenic Amines 2005; 19(4-6): 235–255.]
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“The proposition that animal tests are inherently valid, merely because they are animal tests, is discussed and is rejected. It is concluded that there is no justifiable reason for subjecting new or substantially modified animal test procedures or testing strategies to a validation process that is any less stringent than that applied to non-animal tests and testing strategies.”
[Dr. Balls (2004). Are animal tests inherently valid? ATLA: Alternatives to Laboratory Animals, 32(Suppl. 1B), 755–758.]
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“We believe that although animal experiments are sometimes intellectually seductive, they are poorly suited to addressing the urgent health problems of our era, such as heart disease, cancer, stroke, AIDS and birth defects. Even worse, animal experiments can mislead researchers or even contribute to illnesses or deaths by failing to predict the toxic effects of drugs. Fortunately, other, more reliable methods that represent a far better investment of research funds can be employed.”
[Dr. Barnard and Dr. Kaufman. Animal research is wasteful and misleading . Scientific American, 00368733, Feb97, Vol. 276, Issue 2]
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“Although the mouse provides the most common model for many aspects of the human immune system, the 65 million years of divergence has introduced significant differences between these species, which can and has impeded the reliable transition of pre-clinical mouse data to the clinic.”
[Dr. Brady. Of mice and men: the potential of high resolution human immune cell assays to aid the preclinical to clinical transition of drug development projects. Drug Discovery world 2008/9:74-78.]
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“When one empirically analyzes animal models using scientific tools they fall far short of being able to predict human responses. This is not surprising considering what we have learned from fields such evolutionary and developmental biology, gene regulation and expression, epigenetics, complexity theory, and comparative genomics.”
[Dr. Shanks, Dr. R. Greek, Dr. J. Greek. Are animal models predictive for humans? Philos Ethics Humanit Med. 2009 Jan 15;4:2.]
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“The value of animal experiments for predicting the effectiveness of treatment strategies in clinical trials has remained controversial, mainly because of a recurrent failure of interventions apparently promising in animal models to translate to the clinic.”
[Dr. van der Worp, Dr. Howells, Dr. Sena, Dr. Porritt, Dr. Rewell, Dr. O’Collins et al. Can animal models of disease reliably inform human studies? PLoS Med 2010, 7: e1000245]
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“Patients and physicians should remain cautious about extrapolating the findings of prominent animal research to the care of human disease. […] Poor replication of even high-quality animal studies should be expected by those who conduct clinical research.”
[Dr. Hackam & Dr. Redelmeier. Translation of research evidence from animals to humans. JAMA 2006;296(14):1731-2.]
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“Six volunteers became critically ill during the phase-one test of TGN1412, developed by now-defunct drug firm TeGenero. Although preclinical research on monkeys had shown no sign of danger, the drug provoked devastating immune reactions in the human subjects.”
[Dr. Hopkin. New test could weed out dangerous drug trials. Published online 7 December 2006. Nature]
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“Several investigations have revealed animal carcinogenicity data to be lacking in human predictivity. […]
The likely causes of the poor human predictivity of rodent carcinogenicity bioassays include: 1) the profound discordance of bioassay results between rodent species, strains and genders, and further, between rodents and human beings; 2) the variable, yet substantial, stresses caused by handling and restraint, and the stressful routes of administration common to carcinogenicity bioassays, and their effects on hormonal regulation, immune status and predisposition to carcinogenesis; 3) differences in rates of absorption and transport mechanisms between test routes of administration and other important human routes of exposure; 4) the considerable variability of organ systems in response to carcinogenic insults, both between and within species; and 5) the predisposition of chronic high dose bioassays toward false positive results, due to the overwhelming of physiological defences, and the unnatural elevation of cell division rates during ad libitum feeding studies. Such factors render profoundly difficult any attempts to accurately extrapolate human carcinogenic hazards from animal data.”
[Dr. Knight, Dr. Bailey, Dr. Balcombe. Animal carcinogenicity studies: 2. Obstacles to extrapolation of data to humans. Altern Lab Anim. 2006 Feb;34(1):29-38.]
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“An emerging body of evidence indicates that there are fundamental differences in how the process of tumorigenesis occurs in mice and humans.”
[Dr. Rangarajan & Dr. Weinberg. Comparative biology of mouse versus human cells: modelling human cancer in mice. Nature Reviews Cancer 3, 952-959 (December 2003)]
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“Although these approaches are without exception deemed “very promising” in the literature, it cannot be expected that research on GMO will make any contribution to a new therapeutic strategy in the near future.”
[Dr. Stingl, Dr. Völkel & Dr. Lindl. 20 years of hypertension research using genetically modified animals: no clinically promising approaches in sight. ALTEX 2009; 26(1): 41-51.]
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“By using in vitro laboratory tests, dangers for patients and unnecessary animal experiments can be avoided.”
[Dr. Müller. In vitro biocompatibility testing of biomaterials and medical devices. Med Device Technol. 2008 Mar-Apr;19(2):30, 32-4.]
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“Our reliance on animals to establish safety results in the exposure of clinical volunteers and patients to many treatments that are at best ineffective and at worst dangerous. Take for example the notorious Northwick Park clinical trial drug, TGN1412, that left six young men in intensive care in 2006. This drug was demonstrably safe in monkeys at doses 500 times higher than those that nearly proved fatal to the volunteers. Soon after the disastrous trial, an assay that used human cells was developed to predict such an immune system over-reaction.”
[Dr. Archibald, Dr. Coleman, Dr. Foster. Open letter to UK Prime Minister David Cameron and Health Secretary Andrew Lansley on safety of medicines. Lancet. 2011 Jun 4;377(9781):1915.]
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“The assumption that gene functions and genetic systems are conserved between models and humans is taken for granted, often in spite of evidence that gene functions and networks diverge during evolution. […] Therefore, animal models of gene function and human disease may not provide appropriate information, particularly for rapidly evolving genes and systems.”
[Dr. Vincent Lynch. Use with caution: Developmental systems divergence and potential pitfalls of animal models. Yale J Biol Med. 2009 June; 82(2): 53–66.]
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“For new oncology drugs, only about 5% of investigational new drug applications submitted progress beyond the investigational phase due to a general lack of preclinical systems that can accurately predict efficacy and toxicity of new agents.”
[Dr. Wittenburg & Dr. Gustafson. Optimizing preclinical study design in oncology research. Chem Biol Interact. 2011 Apr 25;190(2-3):73-8.]
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"The complexity of human metastatic cancer is difficult to mimic in mouse models. As a consequence, seemingly successful studies in murine models do not translate into success in late phases of clinical trials, pouring money, time and people’s hope down the drain."
[Dr. Ellis & Dr. Fidler. Finding the tumor copycat: Therapy fails, patients don't. Nature Medicine 16, 974–975 (2010)]
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“Animal testing is not ideal either, as the predictive value of such tests is limited owing to metabolic differences between humans and animals, and many ethical issues are raised by the testing.”
[Dr. Neuzil, Dr. Giselbrecht, Dr. Lange et al. (2012) Revisiting lab-on-a-chip technology for drug discovery. Nature Reviews. Drug Discovery 11:620-632. 10.1038/nrd3799.]
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“Species, and even individual humans, can differ in genetic composition. For example, there may be differences in
The presence (or absence) of certain genes.
The presence (or absence) of certain alleles.
The background genes and modifier genes that influence the genes being perturbed by drugs or disease.
The regulation and expression of genes.
Gene networks.
Alternative splicing, which allows one gene to form or be part of forming many different proteins.
Proteins and protein–protein interactions.
Gene–protein interactions.
Old genes evolving to perform new functions.
Horizontal gene transfer (HGT). HGT occurs when genes from one organism are incorporated into another organism without the recipient organisms being the offspring of the donor. For example, resistance to anti-bacterial drugs can occur through HGT.
Epigenetics. Epigenetics is the relatively new field that studies changes in gene expression that can be inherited and that occur without changing the underlying DNA sequence. For example, because of environmental influences, a regulatory gene may be changed such that it is turned on or off thus allowing a disease to manifest.
The presence of gene and chromosomal mutations such as single nucleotide polymorphisms (SNPs), copy number variants (CNVs), duplications, inversions, deletions, and insertions.
In response to a perturbation to the system, such as a drug or disease, even one of the above differences can result in life or death consequences. Furthermore, convergent evolution can result in the same trait being present but being mediated by very different pathways in different species. Different molecules can also perform the same function. All of these types of differences are present in every species.”
[Dr. Greek R, Dr. Pippus A, Dr. Hansen LA. The Nuremberg Code subverts human health and safety by requiring animal modeling. BMC Med Ethics. 2012 Jul 8;13:16. doi: 10.1186/1472-6939-13-16.]
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"Over 90% of phase 3 clinical trials in oncology fail to meet their primary endpoints despite encouraging preclinical and even early-stage clinical data. This staggering and sobering figure underscores the limitations of existing animal models for the evaluation of potential anticancer agents. The paucity of models is especially apparent with the advent of drugs that target the tumor milieu, or microenvironment, such as antiangiogenics […] immunotherapies and compounds directed against tumor-associated fibroblasts."
[Dr. Singh M, Dr. Ferrara N. Modeling and predicting clinical efficacy for drugs targeting the tumor milieu. Nat Biotechnol. 2012 Jul 10;30(7):648-57. doi: 10.1038/nbt.2286.]
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“Dr. Richard Klausner, then-director of the National Cancer Institute: “The history of cancer research has been a history of curing cancer in the mouse […] We have cured mice of cancer for decades—and it simply didn’t work in humans.””

[Dr. Cimons, Dr. Marlene, Dr.  Josh Getlin, and  Dr. Thomas H. Maugh_II. 2010. Cancer Drugs Face Long Road From Mice to Men  1998]
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“Many are now coming to the realization that, as in other therapeutic areas, the greatest limitation for identifying new drugs for treating cancer are the deficiencies in the animal models used for testing NCEs [new chemical entities, also referred to as new molecular entities or NMEs]”

[Dr. Enna SJ, Dr. Williams M. Defining the role of pharmacology in the emerging world of translational research. Adv Pharmacol. 2009;57:1-30.]
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“The difficulties in predicting drug efficacy from preclinical models have been of concern for more than two decades […] Thus, novel findings apparently related to the systems and targets involved in disease causality; the delineation of the efficacy, selectivity and safety of NCEs; and the predictive relevance of biomarkers and animal model data to the human disease state, even when there is evidence for target engagement in humans, all frequently fail to enhance the success rate for new drug applications (NDAs).”
[Dr. Mullane K, Dr. Williams M. Translational semantics and infrastructure: another search for the emperor's new clothes? Drug Discov Today. 2012 May;17(9-10):459-68. doi: 10.1016/j.drudis.2012.01.004. Epub 2012 Jan 16.]
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“We conclude that even the presence of conserved processes is insufficient for inter-species extrapolation when the trait or response being studied is located at higher levels of organization, is in a different module, or is influenced by other modules.”
[Dr. Greek R, Dr. Rice MJ. Animal models and conserved processes. Theor Biol Med Model. 2012 Sep 10;9:40. doi: 10.1186/1742-4682-9-40.]