Animal testing: Why the 3R’s must prevail

Last month we heard from the BUAV as they put forward the case for the abolition of animal testing. Here the Dr Hadwen Trust suggest that it is not just ethical concerns that should trouble us about the use of animals in research

Each year in the UK alone, millions of animals are used in medical research. With advances in research techniques and an increasing understanding of human disease, alternatives to using animals are becoming more widespread. The pursuit and development of modern techniques which replace the use of animals in research is at the core of our work at the Dr Hadwen Trust for Humane Research (DHT).

The DHT funds and promotes innovative human-relevant research to replace the use of animals and accelerate the progress of medicine. Replacement methods were first defined in 1959 by Russell and Burch as “any scientific method employing non-sentient material which may, in the history of experimentation, replace methods which use conscious living vertebrates”.

Despite the decades which have passed since this concept was defined, animal experiments still remain at very high levels. In 2009, over 3.6 million animals were used in research procedures in the UK.

Everyone wants medical research to succeed in finding cures and treatments for human illnesses and as a medical research charity the DHT is dedicated to the principle of excellence in medical research, but without animal experiments. Following decades of advances in medical research, compelling scientific arguments against animal experimentation have been added to the classical ethical issues surrounding animal use in research. The validity of animal models has been challenged repeatedly, and pursuing research on animals has been shown to often produce conflicting or confusing results, which do not always relate to humans, due to differences between species.

Although animal-based models of many diseases are still the main approach used in medical research, there are currently no available animal models that successfully reproduce human diseases in their entirety. Using animal models for illnesses usually involves artificially inducing some of the symptoms of the human condition, but these methods often fail to replicate the underlying cause. Whereas a range of symptoms might be understood, the causes of human illnesses and their progression are often impossible to identify in animals. In addition, since reactions to new drugs are very difficult to predict and the function of each area of specific organs have not all yet been fully defined, it is often impossible to assess the validity of the results obtained from animal experiments which can therefore be critically misleading.

The animal model has been shown to have misleading effects not only from a researcher’s point of view, but also from a patient’s point of view. Findings from animal experiments that have raised patients' hopes of an imminent cure have often led to disappointment when the promised therapy fails to work in humans. For example, 'strokes' are induced in monkeys and rats by blocking an artery to the brain, causing brain damage. Decades of animal research have produced numerous stroke drugs that protect animals, but none of them have been shown to be fully effective in humans.

As a result the DHT is striving through our work to fund medical research which produces more human-relevant techniques and results, and does not involve animals.

We have seen tremendous achievements in replacing animals in experiments, while improving the quality of research. To name just a few, identification of potential hepatitis C treatments using advanced cell cultures and improved understanding of pre-eclampsia through computer modelling are good examples. Similarly, the development of non-invasive imaging techniques, such as diffusion Magnetic resonance imaging (MRI) or Magnetoencephalography (MEG), have produced major insights into brain function and neurodegenerative diseases.

To further our understanding of diseases and develop new treatments, advanced technologies are now being implemented and new ones developed as described in the following examples:

Human tissue
Studies are now being conducted on human brain tissues from patients to understand the progression of certain diseases and how they spread from one part of the brain to the next. Such studies can only be done using human tissues since the condition does not spread in the same way in the animal brain. The application of these advanced human-relevant approaches is only limited by the availability of human tissue.

Bioinformatics and computer simulation
Increasingly researchers are using computer technology to understand disease mechanism. Computational models are being developed to visualise drugs and other molecules at the molecular level, whilst realistic simulations of human cells, tissues and entire organs are also being engineered. 

Brain Imaging
Non-invasive methods such as MEG have been useful in studying neurological disorders. The DHT is one of the major funding bodies of the MEG facilities located at the Aston Brain Centre, a Centre of Excellence with a 40-year track record of leadership in clinical neurophysiology. MEG is an extremely powerful tool which is being used to understand drug/brain interactions with a particular interest in Parkinson’s disease, epilepsy, stroke and pain across the life span.

System Biology
System biology uses the wealth of data already available to build in silico approaches to diseases, combining mathematical modelling, systems analysis and associated measurement techniques. Computational models of disease will allow multiple in silico investigations of the origin and progression of certain diseases that will provide a platform to researchers to design new experiments and trials.

Despite the undeniable progress of these new approaches which demonstrate what can be achieved, advancement in replacement techniques remains disappointingly slow. The UK Government has gone to certain lengths to encourage researchers to invest in the 3Rs – Replacement, Reduction and Refinement. In 2004, the National Centre for 3Rs (NC3Rs) was created to promote the 3Rs principle in research, and provide the opportunity for scientists to apply for funding to carry out 3Rs research. Unfortunately, this world-leading initiative only represents a small proportion of the total science budget.

The potential of Replacement science to improve the human-relevance of research and reduce the number of animals used has yet to be fully explored and is often over-looked by policy makers and funding bodies.

For academia and industry, the financial burden of maintaining animal facilities, combined with the inadequacy of animal models, should make replacement a priority. Research reviews consistently reveal how badly animal studies relate to human diseases and figures show that the majority of animal tests fail to assess drug safety accurately.

A recent poll by the NC3Rs showed that the awareness of the 3Rs even within the scientific community is very poor. This poll also revealed that even amongst the minority of scientists willing to pursue 3Rs approaches, many hurdles prevented them from developing Replacement approaches. Amongst the encountered obstacles, scientists mentioned the lack of dedicated funding and information together with the tendency of many scientific journals to favour the publication of articles about animal models.

Replacement is the most challenging of the 3Rs. Although Reduction and Refinement are essential, to reduce the number of animals used and their suffering, they rarely result in full Replacement. As defined by Russell half a century ago, they are temporary approaches when Replacement is not yet available. Replacement is the only way forward in order to continue to find cutting-edge techniques which accurately reflect human illnesses.

Unfortunately, with the recent announcement by the UK Coalition Government that it was freezing the science budget, the allocated funding to 3Rs will also suffer.

By replacing animal models, new research techniques have led to more human-relevant results through humane approaches to human disease. Although the development of such new methods often brings new challenges for researchers, it will ultimately result in improving the quality of scientific data and human health, while preserving the lives of animals.