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The use of animals in scientific research: the current situation and non-animal methods

How are animals used in scientific research? Animals are used in research for many different reasons. Table 1 outlines the main ways in which they are used.

the current situation and non-animal methods

The use of animals in scientific research:

Use

Example

Animal ‘models’ of human disease

Transgenic mouse ‘models’ of Alzheimer's disease

Animals as ‘test subjects’ of medicines or techniques for the ‘benefit’ of humans

Wounding mice to test ultrasonic skin stimulation as a healing modality

Animals as ‘test subjects’ of medicines or techniques for the ‘benefit’ of animals

Testing the effectiveness of different painkillers in cats

Animals as 'factories' to generate organs, tissues or cells for therapeutic or research use

Transplantation of pig heart valves into humans

Animals as 'factories' to generate medicines or research materials

Antibodies, serum and other materials used in biomedical research

Animals as ‘tools’ for the education and training of students

Dissections of organs and/or whole animals by biology students

Animals as ‘tools’ for the generation of basic, non-applied scientific knowledge

Research into the role of a gene in the development of the mouth in frogs and mice

Table 1: The main ways in which animals are used in scientific research. Adapted from Greek and Shanks (2009)⁶

To achieve these ends, animals undergo 'regulated procedures'. A regulated procedure is defined under the Animals (Scientific Procedures) Act 1986 as “any procedure applied to a protected animal for an experimental or other scientific purpose, or for an educational purpose, that may have the effect of causing an animal pain, suffering, distress or lasting harm equivalent to, or higher than, that caused by the introduction of a needle in accordance with good veterinary practice”. In 2015 alone, 4.14 million regulated procedures took place in universities (48 per cent), commercial organisations (25 per cent), non-profit organisations (12 per cent) and public bodies (12 per cent) across the UK⁷.


Why is this a problem? The argument against the use of animals in research can be split into two broad categories: ethical and scientific. The ethical argument focusses on animals as sentient beings, and sees their use in scientific research as a violation of their right to a life free from exploitation. This argument applies to all uses of animals in research. The scientific argument is centred around the use of animals as predictive ‘models’ for humans (ie the first two categories described in Table 1). For each example of a drug ‘breakthrough’ emerging from animal research (eg Herceptin), there are many

more examples of drugs that appear promising in non-human animals but prove to be ineffective in man or, worse still, disasters that have occurred when compounds that are safe in non-human animals have deleterious effects in man (eg Vioxx). Since we know this to be the case, it follows logically that we are missing out on potentially safe and effective therapies in man because they are dangerous or ineffective in non-human animals⁸. If animal ‘models’ are only able to predict outcomes in man some of the time, and we can't know in advance when those times are, they are of very limited use⁹.

Why do animal ‘models’ often fail to predict responses in humans? Aside from being a different species, and the anatomical and physiological differences this entails⁹, animals housed in laboratories are a homogeneous population kept under highly-controlled environments. This is in stark contrast to humans, who are varied genetically and in lifestyle, and often have complicating factors such as other illnesses⁸. Where diseases are artificially induced in non-human animals to ‘model’ human diseases, the approach is often reductive and oversimplified, failing to take into account the complex pathogenesis of the disease and the numerous factors that contribute to it. 
Additionally, systematic reviews of animal experiments are finding that studies are frequently poorly planned and designed, rendering their results even less relevant¹⁰.

Though the use of animals in generating basic, non-applied scientific knowledge is not inherently scientifically unsound, it has been argued that the use of sentient animals is particularly difficult to justify where the research is not delivering measurable gains, ie 'saving lives'¹¹. The use of animals in this way is often defended by arguing that basic research eventually translates into medical advances. However, the rate of translation is extremely low, with one review finding that just five per cent of studies of this type actually resulted in commercial development of a drug¹².


What non-animal methods are available? Many methods currently exist that allow animals to be replaced in scientific research, and technologies are improving all the time. Animal Justice Project believes that the replacement of animals in research will accelerate this improvement. Here are some examples of non-animal methods that are available: • Use of cells, tissues and organs that have been grown in the laboratory or obtained post-mortem or from clinical cases. For example, breast tumour biopsy samples have been used to trial new therapies¹³. • Computer-aided drug discovery and development¹⁴. • 'Organ on a chip' technology to mimic tumour environments¹⁵. • Recombinant technology for the production of medicines or research materials. For example, bacteria have been used to produce antibodies¹⁶. • Audio-visual and haptic resources to educate and train students. For example, a haptic simulator has been developed that allows veterinary students to practice rectal palpation in cows without using animals¹⁷.

• Clinical research in human or animal patients with naturally-occurring disease. This encompasses a variety of techniques used to gain more information about clinical conditions, including advanced imaging techniques¹⁸ and genome-wide association studies¹⁹. • Utilisation of patient records to generate data on the prevalance, risk factors and treatment outcomes of naturally-occurring diseases. For example, veterinary records have been used to improve the understanding of mast cell tumours in dogs²⁰. These methods are not just preferable from an ethical point of view; by being more relevant to the species they aim to help, they avoid the unreliability of using animal ‘models’ to predict human responses. Since breeding animals is a slow, costly and laborious process requiring specialist facilities and staff, non-animal methods are also generally quicker, cheaper and more efficient than their animal-based counterparts.


References Elder GA, Gama Sosa MA, De Gasperi R. 2010. Transgenic mouse models of Alzheimer's disease. Mt Sinai J Med. 77 (1): 69-81 2 Roper JA, Williamson RC, Bally B, Cowell CA, Brooks R, Stephens P, et al. 2015. Ultrasonic Stimulation of Mouse Skin Reverses the Healing Delays in Diabetes and Aging by Activation of Rac1. J Invest Dermatol. 135 (11) : 2842-51 3 Slingsby LS, Sear JW, Taylor PM, Murrell JC. 2015. Effect of intramuscular methadone on pharmacokinetic data and thermal and mechanical nociceptive thresholds in the cat. J Feline Med Surg. [Epub ahead of print] 4 Manji RA, Lee W, Cooper DK. 2015. Xenograft bioprosthetic heart valves: Past, present and future. Int J Surg. 23 (Pt B): 280-4 5 Tabler JM, Bolger TG, Wallingford J, Liu KJ. 2014. Hedgehog activity controls opening of the primary mouth. Dev Biol. 396 (1): 1-7 6 Greek R, Shanks N. 2009. FAQs about the Use of Animals in Science: A Handbook for the Scientifically Perplexed. Lanham: University Press of America 7 Home Office. 2015. Annual Statistics of Scientific Procedures on Living Animals Great Britain. United Kingdom Government: Home Office 8 Tyler A. 2015. The Scientific Case Against the Use of Animals in Biomedical Research. Animal Aid 9 Shanks N, Greek R, Greek J. 2009. Are animal models predictive for humans? Philos Ethics Humanit Med. 4:2 10 Pound P, Bracken MB. 2014. Is animal research sufficiently evidence based to be a cornerstone of biomedical research? BMJ. 348: g3387 11 Greek R, Greek J. 2010. Is the use of sentient animals in basic research justifiable? Philos Ethics Humanit Med. 5:14 1

campus@animaljusticeproject.com www.animaljusticeproject.com

Contopoulos-Ioannidis DG, Ntzani E, Ioannidis JP. 2003. Translation of highly promising basic science research into clinical applications. Am J Med. 114 (6): 477-84 13 Hass R, Bertram C. 2009.Characterization of human breast cancer epithelial cells (HBCEC) derived from long term cultured biopsies. J Exp Clin Cancer Res. 28: 127 14 Kapetanovic IM. 2008. Computer-aided drug discovery and development (CADDD): in silico-chemico-biological approach. Chem Biol Interact. 171 (2): 165-76 15 Walsh CL, Babin BM, Kasinskas RW, Foster JA, McGarry MJ, Forbes NS. 2009. A multipurpose microfluidic device designed to mimic microenvironment gradients and develop targeted cancer therapeutics. Lab Chip. 9 (4): 545-54 16 Mazor Y, Van Blarcom T, Iverson BL, Georgiou G. 2008. E-clonal antibodies: selection of full-length IgG antibodies using bacterial periplasmic display. Nat Protoc. 3 (11): 1766-77 17 Kinnison T, Forrest ND, Frean SP, Baillie S. 2009. Teaching bovine abdominal anatomy: use of a haptic simulator. Anat Sci Educ. 2 (6): 280-5 18 Prvulovic D, Bokde AL, Faltraco F, Hampel H. 2011. Functional magnetic resonance imaging as a dynamic candidate biomarker for Alzheimer's disease. Prog Neurobiol. 95 (4) :557-69 19 Do CB, Tung JY, Dorfman E, Kiefer AK, Drabant EM, Francke U, et al. 2011. Web-based genome-wide association study identifies two novel loci and a substantial genetic component for Parkinson's disease. PLoS Genet. 7 (6): e1002141 20 Shoop SJ, Marlow S, Church DB, English K, McGreevy PD, Stell AJ, et al. 2015. Prevalence and risk factors for mast cell tumours in dogs in England. Canine Genet Epidemiol. 2:1 12

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