Cutting edge

December 4, 1998

Finding alternatives to testing new drugs on animals is an uphill struggle, but progress is being made. Paul Skett reports

Should animals be used in testing new drugs if viable, scientifically validated alternatives exist? I doubt whether anyone working in this field of research would answer "yes" to this question. But have we the alternatives to use? The answer is a resounding maybe. There are alternatives - computer simulations, cell culture, human experimentation - but do they give a valid result?

This is the area I have worked in for a number of years - spurred on by the ability to harvest and culture liver cells from animals and man and the thought that we may reduce the number of animals used in research. It seemed easy: one billion live cells from a single rat liver - enough for 1,000 experiments and a saving of 99.9 per cent in animals. But there was a problem. The cells lost their special liver functions in a few hours. They no longer reacted as liver cells and, thus, were of little use. So began the search for a way to maintain vital liver function in the isolated cells. Funding from the European Commission and the Home Office allowed us to continue this work. We found that altering the culture medium, using a basement matrix for the cells to attach to, and growing the cells on a layer of another cell type helped.

The pharmaceutical and contract research industries became interested in a method that offered a way to answer the anti-vivisection movement and reduce the costs of development programmes (cell culture is much cheaper than animal testing).

A European interest group was formed, the Hepatocyte Users Group (HUG), to pool information and resources and tackle the problems of using isolated liver cells (hepatocytes). We have met annually for eight years and have stimulated the formation of an EC working group on liver cells. Many groups in academia and industry now use isolated liver cells in research and development but we still have to find an alternative to whole animals for investigating drug effects on the liver.

We recently turned our attention to human liver cells, which one might think would be the ideal alternative to testing in man. The problems here are different - access to human liver and storage of the huge number of cells obtained. If and when a liver arrives, a successful preparation may give 10-12 billion cells (sufficient for 10,000 experiments) - far in excess of the amount that can be used.

How do we keep them alive and functional? Here the theories and practices of cryopreservation, successfully used already for sperm and eggs, can be employed. We have been involved in a further European study to identify the ideal method of freezing cells at - 186xC. We have succeeded in storing cells for two years and thawing them for subsequent experiments.

The problem of supplies of human liver is becoming acute. Much valuable research material is lost because of the ethical difficulty of asking next of kin for permission to use organs for research. The reluctance on the part of the clinical team to disturb the relatives at their time of loss is understandable. Would it not be more sensible to follow the wishes of the potential donor with permission given in life for the use of tissues after death?

The research group could apply for a project licence for the use of human material, as they need to do for the use of animals - this would alleviate the shortage of human material and allow strict policing of the use of such material and, thus, allow the continued move away from animal testing for new drugs.

Paul Skett, senior lecturer in biomedical and life sciences, University of Glasgow.

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