Will better toxicity testing sound death knell for animal experimentation?

By Wayne Carter, University of Nottingham

Tissue culture
Tissue culture in action!

Well it won’t, completely, but it may go some way to reduce the number of animals used in drug development.  Drugs need to undergo extensive safety and toxicity testing before being made available to the public on the shelves of a pharmacy.

 

Drug development, or the ‘drug pipeline’ as it is known, involves preclinical testing in animals, and then three stages of clinical trials in humans with ever increasing numbers of participants.  This testing can cost millions of pounds, and even then it has a poor success rate, with only ~5-10 % of drugs that start human trials making it to approval.   So for every 20 drugs developed only 1 might have the golden ticket!

Why? Many are just too toxic to humans.  Our liver is our major detoxification organ…hence the one we use and sometimes abuse for metabolising alcohol!  But, did you know the number of people in the USA that are poisoned and experience adverse liver reactions to just paracetamol each year is ~100,000.

Laboratory animals provide a means for testing toxicity prior to undertaking human trials.  The majority of work involves rats or mice, but they have limitations with direct comparison to humans.  Although there has been a slight fall (3%) in the number of animals used in experiments this year according to the UK Government’s annual statistics relating to scientific procedures on living animals, nearly 2 million experimental procedures were still performed.

Neuronal cells grown in culture
Neuronal cells

An alternative to using animals is to use cells grown in culture.  This field has recently advanced with the ability to culture several different cells together in a single dish – think of it as having all the cells (ingredients) that make up an organ all mixed together, just the same as in our bodies.

 

Examples of co-cultures include mixtures of liver cells or mixtures of brain (neuronal) cells, and they can take the form of ‘3D organs’.

So there are now improved cellular models of organs such as livers, and we and others are working on the development of better assays of cell toxicity.  One common mechanism of drug-induced cell toxicity is through damage to mitochondria – the powerhouses of the cell that produce ATP.  Toxicity assays that involve measurements of mitochondrial protein activities using cells grown in culture are now commonplace, and may provide an early warning of cell toxicity limiting the need for animal studies.

Together better organ and tissue models and better toxicity assays should mean less animals are needed in the future for toxicity testing of new drugs.

If you wish to find out more information about animal research you can access more information on the Understanding Animal Research (UAR) website. UAR is a not-for-profit organisation that explains why animals are used in medical and scientific research.

You can find out more information on 3D printed tissues and cells in the August 2016 issue of The Biochemist with a theme of ‘Beyond the Cell’.

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