Dogs and
animal research

Banner image courtesy of: Sanofi.

Why are dogs used in biomedical research?

Dogs are used in biomedical research because they have certain similarities with humans – for example in their genetics, anatomy and physiology – which are not present in almost all other animals. The use of dogs in research serves to benefit not only human health, but also that of dogs themselves.

EU legislation does not allow experimentation on any animal if there is an effective non-animal method available and, dogs are only used when other animal models will not achieve meaningful results. This means they are used in only a very small percentage of procedures. Across the EU more than 90% of animal research is done on mice, rats and fish rather than large animals.

The EU has some of the strictest requirements in the world for the care and use of laboratory animals, and it emphasises that research with dogs is only justified when there are no alternative methods, where the potential benefits are compelling, when it is scientifically, legally and ethically justified, and welfare standards can be met.

Despite the fact that advances in knowledge can now partly be achieved using methods that do not involve animals, the use of dogs will nevertheless continue to be instrumental, even as these newer methods are being phased in, because animals will still be required as references in order to validate non-animal methods to show that they work and can be used without the need for animals in certain circumstances.

The most recent figures for animal use in scientific research in EU member states, showed that dogs accounted for around 0.1% of the total (8,709 dogs out of 8,385,397 animals).

When is it essential to use dogs in biomedical research?

Toxicity tests

For a new drug to reach clinical trials in humans, the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) usually require tests to assess toxicity in both a rodent and a non-rodent mammal to give comparative safety data. The rodent will often be a rat; the other mammal will usually be a dog (although pigs and monkeys are also used).
Many of the procedures are repeat dose toxicity testing, where dogs are used to determine the ‘maximum tolerated dose’, which helps to determine the size of doses for trials in humans.

The European Federation of Pharmaceutical Industries and Associations (EFPIA) has shared case studies that illustrate the value of dogs in toxicity testing, and therefore drug development and safety practices in the clinic. For example, in one case study, dogs were used to assess a compound for its use as a new cancer therapy, with the repeated dose toxicology study showing that the compound could cause severe issues with bleeding – this was not detected in rat studies, but was seen in an early clinical trial, reflecting the predictability of dogs for humans and ultimately leading to the termination of the project.

Basic and translational research

A small number of dogs are also used for basic research and translational/applied research procedures – in other words when biomedical research continues on a fundamental discovery to find an effective use in humans. .

Dogs are used in research on Duchenne Muscular Dystrophy (DMD), which is the most common fatal human genetic disorder diagnosed in childhood – DMD also occurs naturally and is fatal in dogs. Golden retrievers are the best animal for modelling DMD in humans because they naturally develop a mutation in the dystrophin gene, which closely resembles what happens in human disease. For example, a study led by Harvard Medical School investigated two golden retrievers that had the mutation, but remained healthy. This led to the discovery that ‘silencing’ a particular gene could improve the muscles and reverse muscle cell abnormalities in both dogs and zebrafish with DMD.

Dogs are especially suitable for understanding heart problems in cardiovascular studies due to the resemblance in heart connectivity and size to humans. Studies with dogs led to the development of blood transfusion procedures and the creation of the electrical defibrillator to restore normal heart rhythm. More recently, dogs have been used as a model to investigate heart rhythm disorders in different ways; identify genetic risk factors for heart disease, in a study led by EARA member the University of Helsinki, Finland; and to test and validate improvements to the administration of drugs for heart failure, at the National Cerebral and Cardiovascular Center, Japan.

Experiments on dogs led to the discovery of insulin to treat diabetic patients, and dogs continue to be important for improving the management of diabetes, including at the US Department of Veterans Affairs (VA), where they were used to test an insulin pump (a kind of artificial pancreas) that was approved for people with type 1 diabetes in 2016 by the FDA.

The effectiveness of some new cancer drugs are tested in dogs with the same cancers as humans, as an approved drug can then have a benefit for both humans and dogs. In a study at NUS Medicine, in Singapore, researchers tested an approach to trigger the immune system to fight cancer in pet dogs with existing cancer – which is hoped could become a standard treatment option for both humans and dogs.

Although dogs have much shorter lifespans than humans, the fact that they live with people and have similar social and environmental experiences makes them suitable for studying age-related diseases. A study at the University of Bath, UK, and Auburn University, USA, found that dogs as well as cats can provide a better reflection of ageing and, in turn, Alzheimer’s disease than traditionally used species such as mice. Another project, EVOLOR, from Eötvös Loránd University, Hungary, similarly found that dogs shared similarities to humans in terms of ageing on brain activity, cognition, personality and gene expression.

The keen sense of smell in dogs means they can be successfully trained to detect certain diseases, including Covid-19 from urine samples, in a study at EARA member the University of Helsinki, Finland.

See also the Animal Research News section at the bottom of this artilce for other recent research examples:

Beyond results that have shown to benefit our companion animals, it is our hope to extend the therapy to human patients in the future and improve healthcare outcomes for those who have cancer – especially when they have no treatment options left.

Dr Ho Yoon Khei, NUS Medicine

In recent years, the dog has grown to be one of the most important animals for researchers who aim to understand the biological background of complex traits.

Researcher Enikő Kubinyi, Eötvös Loránd University

Pressure by opponents to end research in dogs

The need to use dogs in research can be a controversial subject, and this has attracted significant attention from activists, who often campaign to shut down the facilities that house purpose-bred dogs, without consideration for what would be lost for research and medical advances.

Activists often claim that dogs are housed in poor conditions in these facilities and report violations in animal welfare standards, which has attracted media attention, and there are ongoing efforts by the biomedical community to correct this misinformation and to inform the public of the necessity of dogs for toxicity testing and drug development, and the high standards of care they receive.

Dog-owners who protest against us should remember that all vaccines, worming tablets, antibiotics and other veterinary treatments that they have given to their pets have been tested on dogs like the ones bred here.

Likewise, dogs cannot be used if alternative methods exist, so the price of opposing their use is that new treatment for diseases like cancer and heart disease cannot be developed.

MBR Acres, UK laboratory animal breeder

Medical treatments to help dogs

As dogs have been involved in the development process of nearly all new drugs, it is often a relatively small step to understand where human drugs might help dogs and to therefore adapt them for veterinary medicine. Just like humans, dogs suffer from cancers, heart diseases, diabetes, joint disease and many other conditions. Research involving dogs and other species of animal enables the development of new safe and effective veterinary medicines that improve the health and welfare of animals worldwide.

A US study at Yale School of Medicine developed a cancer vaccine that was able to slow, or halt the progression, of certain cancers in pet dogs in multiple successful trials. Meanwhile trials of another vaccine (Griffioen) in pet dogs with bone or bladder cancer, by researchers in the Netherlands, including EARA member Maastricht University, showed that it could extend survival and in some cases restore health.

The Maastricht researchers treated 35 dogs, suffering from bladder and bone cancer, with the Griffioen vaccine – half of them survived to the end of the 400-day test period, and two of them fully recovered. Among the dog patients was Rax, a 10-year-old dog, who had developed bone cancer. After treatment his tumours disappeared and Rax returned to normal health.

Beagles in a research facility with animal technician caretaker

Many conditions dogs experience are very similar to equivalent problems faced by humans and other species and so the research undertaken in dogs can help in development of new treatments for other veterinary patients and for human patients.

Royal Veterinary College, University of London

Laboratory beagles with animal technician. Image credit: Understanding Animal Research

Rax is still so strong and sprightly, we wanted to give him a chance. The most important consideration was whether he would still have quality of life after the operation. Looking back, we made the right choice; he is his old self again.

The owner of Rax

What is being done to replace and reduce the use of dogs?

EU Directive 2010/63, on the protection of animals used in scientific procedures, took effect in Member States on 1 January 2013 and since then the Directive has improved animal welfare standards and enforced the application of the 3Rs (Replacement, Reduction and Refinement) when using research animals, across the EU.

In tests to assess the toxicity of drugs, regulations typically require both a rodent (mice or rat) and a non-rodent species, with the latter commonly being dogs, pigs or monkeys. However, in an initiative led by the UK National Centre for the 3Rs (NC3Rs), in collaboration with the pharmaceutical industry, evidence has been found that for certain biological drug molecules, such as monoclonal antibodies, only a rodent may need to be used in toxicity tests. This could reduce the use of dogs as the secondary test animal for this purpose – monoclonal antibodies are commonly used biological therapies, sometimes developed from animals, and work as part of the body’s immune system to detect and eliminate foreign material, such as viruses.

Pigs are also increasingly emerging as an alternative large animal model that can replace dogs in certain studies, such as in surgical training, wound healing, organ transplantation and drug testing.

The NC3Rs has also funded the development of ‘virtual’ dog organs and tissues to assess toxicity in place of real animals, which is an ongoing project.

Non-animal approaches are also showing promise in finding canine treatments, such as for skin conditions. The WowWowSkin project, at the Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB), Germany, succeeded in creating a lab-grown skin that mimics real canine skin, to allow safety assessments for conditions such as atopic dermatitis, that affects up to 15% of dogs.

A method has been introduced for keeping muscle cells healthy for two weeks instead of 24 hours, meaning many more compounds can be tested on cells supplied from a single dog.
In educational and training settings dogs have been replaced with life-like models where students can learn the surgical procedures and techniques of neutering. These models have realistic organs including a urinary bladder, ovaries, simulated blood and fat tissue.
The effective management of breeding colonies to reduce overbreeding helps to reduce overall dog numbers in research. This can be achieved by having a stronger focus on breeding dogs based on actual demand for research, and maintaining high standards of care and welfare to ensure animals do not experience unintended health issues that make them unsuitable for research. This then also helps to ensure that studies in dogs are highly standardised to avoid the need to repeat studies unnecessarily, in turn reducing the overall numbers of dogs used.

Reducing severity in dog research

As part of the 3Rs principle, there are also continuous efforts by scientists and laboratory staff to reduce the severity levels of dog studies and improve animal welfare by minimising any harm or pain they might experience. This can be done by refining how studies are designed and carried out through, for example, greater sharing of data among research groups.

Bile Duct Cannulation is a test on dogs (and other large animals) that investigates how certain drugs leave the body via bile (a digestive fluid). Understanding this provides key insights into how long a drug remains inside the body and where it accumulates, and therefore how much of a therapeutic effect it is having. A less invasive procedure to collect bile from large animals, termed ‘ultrasound-guided cholecystocentesis’ has been developed and validated. In this procedure, ultrasound is used to guide a needle through the liver and into the gall bladder, allowing for precise bile sample collections.

With this refined method, it is now possible to safely and efficiently obtain bile samples from dogs and monkeys without the previous harmful effects.

Dogs are sometimes used for telemetry, (where data is collected and analysed remotely) to provide insights into how organs (such as the heart) perform, for example by monitoring vital signs. This is a commonplace practice for certain studies, such as toxicology, to assess the full effect of drugs on the body. Wireless devices take these body measurements from the dogs and then transmit the data to a receiver – increasingly, non-invasive devices are being developed and used, such as telemetry jackets, and this also means that dogs can be reused for telemetry studies without harm.

Laboratory beagles playing with technician. Image credit: Understanding Animal Research

How are dogs cared for in research?

There are ongoing efforts by the EU to improve dog welfare including improving housing conditions and daily care handling as well as training dogs to reduce levels of stress during experimental procedures. In these facilities, as well as any other animal facility, veterinarians are on hand seven days a week, and in both the EU and UK, it is a legal requirement that all staff are trained specifically in the care of dogs.

Dogs are a well-understood animal, and it is relatively easy to provide them with good welfare and to be confident that they are happy and well-looked after. All dogs housed at both research and breeding facilities are also given access to play areas for mental and physical stimulation, while pregnant dogs are carefully monitored to ensure the health of the mother and her litter, with improved housing conditions close to delivery and during whelping.

See the video below of a UK facility of EARA member Marshall BioResources,
from Understanding Animal Research

Dogs shall where possible be provided with outside runs. Dogs shall not be single-housed for more than four hours at a time. A procedure is considered severe if a dog is kept in complete isolation for prolonged periods.”

EU Directive 2010/63 on the use of animals for scientific purposes

Are dogs rehomed after use?

Healthy and well-socialised dogs are increasingly rehomed and more programmes are being developed to allow more and more dogs to go to suitable homes after a research study is finished.

The EU Directive 2010/63 on animals used for scientific purposes states: Should Member States allow rehoming, it is essential that the breeder, supplier or user has a scheme in place to provide appropriate socialisation to those animals in order to ensure successful rehoming as well as to avoid unnecessary distress to the animals and to guarantee public safety.

There are numerous ongoing efforts – many of them funded – to minimise the number of dogs in research studies and toxicity tests wherever possible, as well as approaches to maximise their wellbeing. While these diverse initiatives are actively contributing to the replacement, reduction and refinement of dogs, their use remains essential in both basic and translational research for the foreseeable future, since there are still research areas that benefit specifically from the use of these animals, that other species cannot fill.

Due to the risk of misinformation about the necessity of dogs in research, which can mislead the public, it is critical that the biomedical community continues to advocate for the responsible and regulated use of dogs for scientific discovery and medical developments.