Dr Katy Taylor, director of Science and Regulatory Affairs at Cruelty Free International discusses the use of dogs within toxicology assessments and why change is needed.
Technology creators have been asked to create virtual dogs to help predict the adverse effects of drugs before they are used in humans as part of the ‘Virtual Second Species’ challenge recently launched by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs).
The challenge is one of the NC3Rs CRACK IT competitions covering animal use in toxicology and environmental risk assessment.
The idea would be that if successful, these virtual dogs could be used to replace experiments on live dogs of which there were 4,340 in 2020 in the UK.
Due to the large amount of data collected on dogs in the decades in which they have been used in experiments, it is argued that virtual dogs could be used to predict unexpected and detrimental effects on human health of drugs in development.
However, whilst virtual dogs are clearly preferable to live dogs in laboratories, why would we want to use the limited funding available for non-animal methods to replicate testing on dogs when we could more reliably be investing in doing the same for humans?
Most experiments carried out on dogs are for testing the safety of human and veterinary drugs and agricultural products required by regulatory agencies worldwide. Dogs are often used as what is called the second species in toxicity tests after experiments have already been carried out on mice or rats.
But dogs are not and can never be substitutes for humans. They react to drugs differently from humans. In contrast to the belief that toxicity seen in dogs means that it is likely to also be present in humans, there is in fact nor clear pattern in terms of types of toxic effects or types of drugs.
Crucially, the absence of toxicity in dogs provides essentially no insight into the likelihood of toxicity in humans. As the absence of toxicity in animals is the critical factor for the progression of a new drug into clinical (human) trials, this has extremely important implications for pharma and for drug development. Drug testing on live dogs is neither morally, nor scientifically justifiable, and testing on virtual dogs is similarly scientifically unjustifiable.
Data from peer-reviewed work done by Cruelty Free International in 2015 and published in the FRAME scientific journal ATLA showed that a successful test on a dog increases the prior probability of no adverse reaction in humans by just two percentage points, e.g., from 70% to 72%.
In comparisons between humans and five species - dogs, monkeys, rabbits, mice and rats - tests on dogs were the second least reliable in predicting toxicity in humans. Monkeys, the ‘least different’ species from humans, were the least reliable.
The arguments in favour of animal testing are outdated yet little has changed for animals in laboratories worldwide, despite incredible advances in science and opposition from the public. Nearly three million animals continue to suffer in Britain’s laboratories every year – despite the fact that 92% of drugs that pass animal trials fail in humans, either due to lack of effectiveness or safety concerns. Recent polling carried out by YouGov for Cruelty Free International shows that 80% of the British public find experiments on dogs unacceptable.*
We desperately need to accelerate the transition to animal-free research and regulatory testing, which recognises not only the shortcomings of animal testing but also the huge benefits of switching to human-relevant methods.
So yes, let’s embrace digital twins, but let us do so with humans, and with the real science of the future. It could be a huge step forward for animals in laboratories, but also for how we test drugs and medicines that work better for people.
*All figures, unless otherwise stated, are from YouGov Plc. Total sample size was 1,765 adults. Fieldwork was undertaken between 13th - 14th September 2021. The survey was carried out online. The figures have been weighted and are representative of all GB adults (aged 18+).
A petition calling for a phaseout of animal testing can be found here - https://petition.parliament.uk/petitions/590216