Science In Transit; The Move Away From Animals In Research

The inescapable truth is that attempting to model human diseases in non-human animals will always be problematic, and can delay progress in finding much-needed cures. And most importantly, these proposals miss the opportunity to stop throwing good resources after the bad, to focus on a transition away from the failing animal models and toward a future of effective cures.

This month I was invited by the European Commission to speak on a scientific panel at the conference Non-Animal Approaches - The Way Forward. The event was organised as part of the EU's response to the citizen's initiative 'Stop Vivisection,' which presented more than one million supporting signatures from across the EU to the European Commission in May 2015, calling for an end to animal experiments.

At face value, this conference was ideal for me. My scientific career has been dedicated to developing practical tools for studying and developing treatments for human disease without harming animals. I am not alone in this. Recent decades have seen enormous strides in the development of non-animal technologies. These tools are known to be more relevant and predictive than ineffective, harmful animal research.

Animal research certainly fails animals, in terms of the distress and suffering caused, and just as importantly, animal research often fails people, too, in terms of the slow, unproductive route to useful treatments. More than 90 percent of drugs that have passed animal trials for safety and efficacy are not successful in treating the human disease for which they are intended.

There are clearly issues on the "translation" of results from other species to humans, but there are also issues with the conduct and reporting of much of the animal research. For example, more than 80 percent of studies using animals demonstrate bias in their choice of experimental groups, such as the choice of animals for a particular study. Animal research has a huge gender bias; eight out of ten experiments only use male animals. This occurs even for diseases which are more prevalent in women, and it should go without saying that modelling female diseases with male animals does not make any sense. Given the rampant selection bias that pervades so much research using animals:

1.Millions of animals are experimentally manipulated, operated on, treated with test compounds and otherwise harmed, stressed and distressed to no appreciable result;

2.Less than 20 percent of published animal research is discriminating, rigorous and trustworthy.

There are guidelines on the reporting of animal experiments that aim to improve the quality of science, and which could in theory lead to a reduction in animal use. However, whilst the guidelines are endorsed by more than 300 scientific publications, uptake has been slow. Some funding bodies require their use, yet animal researchers have no legal obligation to adopt the guidelines before being granted permission to use animals. Issues of biased reporting, skewed results, and ultimately the waste of millions of animals' lives, remain.

Surely we can all agree that replacement of animals in testing and research is morally, ethically and scientifically the only way forward. A recent market research poll, commissioned by the UK's Department of Business, Energy and Industrial Strategy, indicates that more than a quarter of UK citizens would support an outright ban of the use of animals in research. In November this year, a publication in the scientific journal Drug Discovery Today used expert analysis of five human disease areas to show that animal models have failed to provide answers or treatments for any of them. This paper calls for a transition away from failing animal models towards human-relevant methods.

Unfortunately, rather than focus on a future of non-animal solutions, the conference I attended last week spent entirely too much time trying to fix the broken wheel of animal experimentation. The well-substantiated findings that research using animals is 1) failing, 2) frequently unreliable, and 3) often does not generate reproducible results, were acknowledged; however, solutions proposed tended to focus on propping up the failing system, rather than accepting the fact that a fundamental shift in paradigm back to human biology is what's truly needed.

The inescapable truth is that attempting to model human diseases in non-human animals will always be problematic, and can delay progress in finding much-needed cures. And most importantly, these proposals miss the opportunity to stop throwing good resources after the bad, to focus on a transition away from the failing animal models and toward a future of effective cures.

Animal replacement remains the most promising way forward. The UK published its delivery plan to reduce animals in research in 2014, whilst earlier this year the Netherlands opened discussions about phasing-out animal testing by 2025. Enormous investments have been made in developing more promising solutions, including EUToxRisk to find non-animal solutions for chemical safety assessment. In the US, a joint investment by the National Institutes of Health and Defense Advanced Research Projects Agency is building mini-organs and linking them together in a system they are calling "human-on-a-chip." These are the types of investments that will bring light to the future of medicine and environmental safety.

The final report of the European Commission conference is yet to be published. We hope that the key replacement message will not be lost, and that we will see acknowledgement of the fact that animals do not model human disease and that the more we invest scarce public health resources in these failing animal models, the further we get from understanding human disease mechanisms. Transitioning away from failing animal models to human-based approaches to develop medicines for human disease must become the central thread of 21st century research.

Finally, it takes from 3-5 years and millions of dollars to put one chemical substance through a battery of animal safety tests (producing results that predict human outcomes around 50-60% of the time). Using new non-animal alternative test systems, it would take an average of twenty minutes and $5,000 to test a chemical producing results that are currently already as predictive as animal tests but that are improving rapidly as we extract more meaning from the huge amount of new data produced in these non-animal systems.

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