Dogs in scientific research

Highlights

  • Over 100,000 dogs are used in scientific research globally each year
  • The most common use is regulatory safety testing of therapeutic medicines
  • The beagle is most commonly used in research because of the volume of backdata available, temperament and size

 

On this page:

 

Why are dogs used in scientific research?

 

Dogs are used in research for a variety of reasons. The purpose of the research might be to better understand dogs' health and diseases, which would not be possible without studying dogs. Psychological research might use dogs because of their cognitive similarities to humans, or to improve their wellbeing or interactions with humans. Medical research may use dogs because they have a number of similarities to humans and our close evolutionary relationship.

 

what is a regulated procedure?

 

A dog is trained to comply with regulated procedures

 

In the UK's legislation - the Animals (Scientific Procedures) Act (1986, updated 2012) - a regulated procedure is defined as any procedure which "has the potential to cause pain, suffering, distress of lasting harm". This means that all procedures which have the potential to negatively impact on dog welfare are regulated under A(SP)A - this includes everything from a blood sample from the delivery of a test compound. When we talk about dog uses in scientific research on this website, we are mostly referring to research which involves regulated procedures (or their equivalent). You can find out more about the legislation and regulation of animal use in scientific research here.

 

SEVERITY

 

The severity of procedural harms (i.e. excluding harms caused to animals as a result of nonprocedural events such as transport and housing) is assessed as one of five categories as follows. The severity reported in the annual statistics reflects the highest level of severity experienced by an individual.

From 2014, changes to EU legislation mean that actual severity must be reported, which reflects the highest severity of the procedure, including an accumulation of lesser events. This is in contrast to an estimate of average severity or the average severity at the end of the procedure.

Information on severity assessment from the European Commission

 

The following definitions of each of the categories of severity are laid out in A(SP)A (1986, revised 2012).

Sub-threshold It is possible that procedures authorised under a project licence could result in below threshold severity. These will be few, but will occur when it was considered that a procedure might have caused above-threshold pain or suffering, but in retrospect this did not occur for some or all of the animals involved.
Non-recovery A classification of non-recovery is used if an entire procedure is carried out under general anaesthesia and the animal does not recover. It includes unintended death of animals on recovery protocols while under anaesthesia, provided that no regulated procedures had been carried out prior to the induction of anaesthesia.
Mild The key characteristic of mild procedures is that any pain or suffering experienced by an animal is, at worst, only slight or transitory and minor so that the animal returns to its normal state within a short period of time.
Moderate The characteristic of moderate procedures is that they do cause a significant and easily detectable disturbance of an animal's normal state, assuming that appropriate monitoring systems are in place and that they are used by trained and competent staff.
Severe The characteristics of severe procedures are that they cause a major departure from the animal's usual state of health and well-being. It would usually include long-term disease processes where assistance with normal activities such as feeding and drinking are required or where significant deficits in behaviours/activities persist.


The definitions of severity limits vary in national legislation. For example, the USDA's annual statistics classify severity by pain level and whether analgesia was administered, while the CCAC categorises severity by invasiveness. The table below (adapted from Prescott et al., 2004[1]) indicates how clinical signs of severity may present in the dog.

 

SOURCES

 

The sources of dogs used in scientific research varies considerably according to national legislation. Within the EU, it is a legal requirement to obtain dogs from a designated or registered breeder (equivalent to a Class A breeder in the USA). The number of dogs sourced from outside the UK has increased over the past two decades, most likely because of changing industry demands. Many companies previously kept their own breeding colonies but changes in industry have lead to increasing outsourcing to commercial breeders. When dogs are sourced from outside the UK, it should be ensured that the dogs have been bred under the standards equivalent to those in the UK and that journey times and stress from transport are minimised.

The table below compares sources of dogs (adapted from Prescott et al., 2004 [1]).


 

 

Dog use in scientific research

 

In order to understand why dogs are used in scientific research, we need to look at why scientific research is conducted and what we mean by scientific research.

 

regulatory research: SAFETY ASSESSMENT OF MEDICINES AND OTHER NCES

 

As is evident in statistics on animal use, safety assessment studies are the most common use of dogs in scientific research, usually accounting for 60-85% of dog use. This makes understanding safety assessment studies very important to understanding how to improve dog welfare.

Before humans are exposed to new chemical entities (NCEs) in clinical research, regulatory standards must be met. This includes preclinical safety testing. The guidelines which regulate this research are set out in the International Conference on Harmonisation (ICH) and are transcribed locally in individual countries. These are accepted standards in most countries and describe the standards of research that must be met before NCEs can be brought to market to keep us safe. Some preclinical research can be conducted using computer modelling or in vivo research, but all NCEs must be tested in a rodent and nonrodent species before they can be tested on humans to comply with regulations on safety testing. The types of studies conducted are described in the table below. Smith et al [2] provides a detailed description of studies using dogs, including steps which can be taken to minimise and optimise dog use.

Non-clinical development covers all studies ‘before man’, first human exposure, although animal studies may be conducted along-side clinical studies, with the aim being to explore the mechanism of action, potential toxicity and pharmacokinetics, known as ADME: absorption, distribution, metabolism, and excretion [3]. The development of new medicines destined for human use evolves from discovery, through several levels of safety and efficacy testing, before being determined suitable for testing in human clinical trials.

The first in vivo trials will usually be a small, pilot study in a rodent species (and most often mice), followed by a toxicity study of one- or three-month duration. Longer-term studies are indicated where the medication is considered for long-term use in humans. Progression from the rodent to non-rodent models occurs if the observed side effects are deemed acceptable for the level of benefit obtained from the compound’s use. ICH guidelines “Non-Clinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals” [4] are the standard by which testing is conducted. The types of study conducted in the dog are described in the table below. Smith et al [2] provide a detailed description of studies using dogs. and steps which can be taken to minimise and optimise dog use.

Dogs are the preferred nonrodent model for preclinical studies for a number of reasons. Although nonhuman primates are physiologically more similar to humans, it is ethically unacceptable to use nonhuman primates unless absolutely necessary, and as dogs are better adapted to live in kennel situations in close contact with humans, they may experience less stress as a result of captivity. Dogs have a very close shared evolutionary history with humans which has resulted in the environment having similar effects on our health and disease processes (see Dogs) and they make better models of humans than rodents (see Good Science). Olson [5] found that the concordance of toxicity between humans and rodents was 43%, while with dogs, it was 63%.

The dog is considered the “default non-rodent” [6], and has been since the 1950s and 1960s [7,8]. Indeed, Gad [8] reports their use in medical testing dating back to the 17th Century; the availability of historical data being one of prevailing reasons for dogs’ continued use. Phillips et al.[9] state that the choice of non-rodent species should be based on scientific and ethical considerations, however the dog is commonly used because of its size, temperament and the volume of backdata available [7]. The table below, adapted from Gad [8] Box and Spielmann [7] and Slaughter et al. [10] highlights some of the common advantages and disadvantages of the dog model. It should be noted that many of these related to the ease of conducting procedures and not to the quality of data or concordance with human data.

 


Selective breeding and a shared evolutionary environment have resulted in the dog being an invaluable model for human disease and toxicity, due to similar influences acting on genetic evolution. A study commissioned by the International Life Sciences Institute [5] found that dog studies were considerably more predictive of human toxicity than rodent studies: a concordance rate with clinical trials of 71% was found for combined rodent and non-rodent studies, with non-rodent studies alone being predictive for 63% of human toxicity. The need to Refine dose ranges so that the necessary clinical signs of toxicity can be identified without causing undue suffering has been identified, with guidance produced by NC3Rs on dose selection [12]. A similar concern with body weight loss was addressed in a study by Chapman et al. [13] with Refined limits being applied to loss in body weight (less body weight loss permitted) without loss of scientific information relating to toxicity.

Sequencing of the canine genome by the National Human Genome Research Institute [14] suggests that the dog is an “unrivalled model for the study of human disease” (pp. 112) and that dogs share 220 homologous hereditary diseases with uniform genetic mutations [15]. In particular, dogs have been established as sensitive models for cardiovascular and nervous system changes [16]. Welfare concerns have meant that nonhuman primate use is decreasing, and as such, the dog is becoming the preferred non-rodent model.

Dogs are also used for agricultural and industrial chemical testing, veterinary medicine development and testing of medical devices and pet food products [15], which although investigating different parameters from non-clinical safety testing, still often require that the subjects are a healthy, valid model of the human or dog target organism.

In total, around 12 million animals are used in the EU each year, and 17 million in the US [17] ; dogs constitute only a small proportion of the total animals used. Of all dogs used in studies conducted during the drug development process in the EU, approximately 50% are used for regulatory safety assessment (see below), a smaller percentage than in the UK. Regulatory safety assessment refers to the range of legal requirements for assessing safety and efficacy prior to human exposure and is governed by the International Convention on Harmonisation (ICH) guidelines.

Furthermore, the current protocol for safety assessment of new medicines as set out in the ICH guidelines has changed little over the past decades, in part due to the process required to validate new protocols [3].

Dogs represent around 0.09% of dogs currently used in Great Britain, potentially resulting in an additional 8 dogs used for each pesticide tested. Within the EU, the REACH (Registration, Evaluation, Authorisation and Restriction of Chemical Substances) legislation will lead to an increase in the safety assessment of pesticides and other chemicals and as such dog use is set to increase in coming years; Pellegatti (2013) estimates that up to 17.6 million animals may be needed to fill this knowledge gap.

 

Safety assessment is not restricted to the development of new medicines. Non-pharmaceutical products such as agricultural products (mainly pesticides and biocides), food additives and industrial chemicals are also tested extensively for safety according to legal requirements. Dogs are also used in the development of new methods of testing for chemical safety.

Box and Spielmann (2005) report that at least 9,000 animals are needed for each pesticide developed, at least 75% of which represents investigation on reproduction and development. The use of dogs in the safety assessment of medicines may also increase due to a change in legislation requiring “juvenile toxicity” data, safety testing in young animals for medicines which may be used in juvenile humans (Pellegatti, 2013). This potential increase in dog use, in addition to the current global use, suggests that it is critically important to address the current knowledge gap regarding welfare needs and assessment, and the impact of welfare on quality of data output. A clear understanding of the factors which can potentially reduce welfare in the dog is needed along with the promotion of better welfare, before addressing the impact on data output quality.


 

PSYCHOLOGICAL RESEARCH (HUMAN AND DOG)

 

Five dogs undergoing experiments on gastric secretion in the Physiology Department, Imperial Institute of Experimental Medicine, St Petersburg. The laboratory of Ivan Petrovich Pavlov (1849-1936). This file comes from Wellcome Images, a website operated by Wellcome Trust, a global charitable foundation based in the United Kingdom. Refer to Wellcome blog post (archive).

Dogs have long been used in psychological research. From Pavlov's studies of learning to Fox and Stelzner's exploration of early experiences, much psychological research has aimed to uncover processes which explain human psychology. Today's modern cognitive research in dogs is a far cry from research such as Seligman's learned helplessness experiments. Dogs are now studied lying awake in MRI scanners, observing facial expressions from screens and following gestures. In much of this research, dogs are trained to comply and many studies do not contain procedures which would fall under the definition of regulated procedures (with the ability to cause pain, suffering, distress or lasting harm).

 

VETERINARY RESEARCH

 

A veterinarian stitching a dog, after surgery. Photo credit: Chetblong.

Dogs not only undergo research to answer questions about human health, but also to increase our understanding of dog health and disease processes. While clinical veterinary research may take place in pet dogs attending veterinary clinics, basic research which aims to better understand the processes underlying diseases may take place in laboratory-housed dog populations.

 

 

basic, or FUNDAMENTAL, and translational RESEARCH

Photo credit: Understanding Animal Research

Basic, or fundamental, medical research is conducted to better understand how the body works, which might include discovering new disease processes, or better understanding disease mechanisms to develop therapies. In research which uses dogs, fundamental research may seek to better understand disease processes in dogs, or diseases which are also found in humans. There are a number of diseases which occur in humans and dogs, such as muscular dystrophy.

 


1. Prescott, M., Morton, D. B., Anderson, D., Buckwell, A., Heath, S., Hubrecht, R., Jennings, M., Robb, D., Ruane, B., Swallow, J. & Thompson, P. (2004). Refining dog husbandry and care: Eighth report of the BVAAWF/FRAME/RSPCA/UFAW Joint Working Group on Refinement. Laboratory Animals, 38 (SUPPL. 1), S1:1-S1:94.

2. Smith, D., Combes, R., Depelchin, O., Jacobsen, S. D., Hack, R., Luft, J., Lammens L, von Landenberg F, Phillips B, Pfister R, & Rabemampianina, Y. (2005). Optimising the design of preliminary toxicity studies for pharmaceutical safety testing in the dog. Regulatory Toxicology and Pharmacology, 41(2), 95-101.

3. Pellegatti, M. (2013). Dogs and monkeys in preclinical drug development: The challenge of reducing and replacing. Expert Opinion on Drug Metabolism and Toxicology, 9 (9), 1171-1180.

4. International Conference on Harmonization. (2008). Non-Clinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals.

5. Olson, H., Betton, G., Robinson, D., Thomas, K., Monro, A., Kolaja, G., ... & Dorato, M. (2000). Concordance of the toxicity of pharmaceuticals in humans and in animals. Regulatory Toxicology and Pharmacology, 32(1), 56-67.

6. Smith, D., Broadhead, C., Descotes, G., Fosse, R., Hack, R., Krauser, K., Phillips, B.,
Rabemampianina, Y., Sanders, J., Sparrow, S. et al. (2002). Preclinical safety
evaluation using nonrodent species: An industry/welfare project to minimize dog
use. ILAR Journal, 43 (Suppl 1), S39-S42.


7. Box, R. & Spielmann, H. (2005). Use of the dog as non-rodent test species in the
safety testing schedule associated with the registration of crop and plant protection
products (pesticides): Present status. Archives of Toxicology, 79 (11), 615-626.


8. Gad, S. C. (2006). Animal models in toxicology. Boca Raton, CRC Press Taylor and Francis Group.

9. Phillips, B., Smith, D., Combes, R., G. Descotes, S. J., Hack, R., Kemkowski, J., Krauser, K., P_ster, R., Rabemampianina, Y., Sparrow, S., Stephan-Gueldner, M. & von Landenberg, F. (2004). An approach to minimise dog use in regulatory toxicology: Production of a best practice guide to study design. ALTA, 33 (Supplement 1), 447-451.

10. Slaughter, M., Birmingham, J., Patel, B., Whelan, G., Krebs-Brown, A., Hockings, P. & Osborne, J. (2002). Extended acclimatization is required to eliminate stress effects of periodic blood-sampling procedures on vasoactive hormones and blood volume in beagle dogs. Laboratory Animals, 36 (4), 403-410.

11. Olson, H., Betton, G., Robinson, D., Thomas, K., Monro, A., Kolaja, G., Lilly, P., Sanders, J., Sipes, G., Bracken, W. et al. (2000). Concordance of the toxicity of pharmaceuticals in humans and in animals. Regulatory Toxicology and Pharmacology, 32 (1), 56-67.

12. Robinson, S., Chapman, K., Hudson, S., S, S., Spencer-Briggs, D., Danks, A., Hill, R., Everett, D., Mulier, B., Old, S. & Bruce, C. (2009). Guidance on dose level selection for regulatory general toxicology studies for pharmaceuticals. London, UK: NC3Rs/LASA.

13. Chapman, K., Sewell, F., Allais, L., Delongeas, J.-L., Donald, E., Festag, M., Kervyn, S., Ockert, D., Nogues, V., Palmer, H. et al. (2013). A global pharmaceutical company initiative: An evidence-based approach to define the upper limit of body weight loss in short term toxicity studies. Regulatory Toxicology and Pharmacology, 67 (1), 27-38.

14. Starkey, M. P., Scase, T. J., Mellersh, C. S. & Murphy, S. (2005). Dogs really are man's best friend - Canine genomics has applications in veterinary and human medicine! Briefings in Functional Genomics & Proteomics, 4 (2), 112-128.

15. Zurlo, J., Bayne, K., Cimino Brown, D., Burkholder, T., Dellarco, V., Ellis, A., Garrett, L., Hubrecht, R., Janus, E., Kinter, R., Luddy, E., Meunier, L., Scorpio, D.,
Serpell, J. & Todhunter, R. (2011). Critical evaluation of the use of dogs in
biomedical research and testing. ALTEX, 4, 355.


16. Moscardo, E., Fasdelli, N., Giarola, A., Tontodonati, M. & Dorigatti, R. (2009). An optimised neurobehavioural observation battery integrated with the assessment of cardiovascular function in the beagle dog. Journal of Pharmacological and Toxicological Methods, 60 (2), 198-209.

17. Taylor, K., Gordon, N., Langley, G. & Higgins, W. (2008). Estimates for worldwide laboratory animal use in 2005. ATLA, 36 (3), 327.