Research Intelligence - For all their sakes, and science's too

Under current rules, UK scientists must strive to reduce the numbers of animals they use in research as well as limiting their suffering.

But on 17 May, legislative proposals were announced with respect to the implementation of a new European directive on animal research that means the UK must actively develop and promote alternatives, starting in 2013.

The move is likely to propel into the limelight a small government body designed to do this that has been growing steadily since its creation in 2004 but that remains unknown to the public at large - the National Centre for the Replacement, Reduction and Refinement of Animals in Research, or NC3Rs.

According to Mark Prescott, head of research management and communications at NC3Rs, the idea of the "3Rs" in animal research is not new.

In fact, the same words were first set out in a book by academics William Russell and Rex Burch in 1959 under the auspices of the Universities Federation for Animal Welfare.

However, for decades it was rarely seen as more than a good ethical framework, until a House of Lords report in 2002 highlighted that reducing and refining animal use could also lead to more predictable, more reliable and faster research.

Dr Prescott said this had caused a significant change in research practice in the past few years.

Since its inception, the NC3Rs, funded by the government with a small amount of charitable support, has developed six funding schemes, spending a total of £25 million.

This week, the centre announced four new £65,000-a-year fellowships for early career researchers, named after Lord Sainsbury of Turville, the former science minister who championed the NC3Rs.

Adjanie Patabendige, a postdoctoral researcher at the University of Liverpool and an NC3Rs Sainsbury fellowship winner, said that although some experiments will continue to need animals, applying techniques like hers more widely would have economic benefits.

"It will save money in the long run because animal experiments are complicated and certainly not cheap. I think you have to think more long term, not look for a quick fix," she said.

Dr Patabendige is developing a 3D model of the barrier that protects the brain using donated human cells.

She hopes to use it to study how viruses such as Japanese encephalitis infect the brain, potentially replacing some of the 3,500 rats, mice and monkeys used in similar research in the past 10 years.

"The problem is, we don't have good cell culture models, so scientists don't have any choice but to use animals," she said.

"But it's difficult to study this in animals because viruses would affect humans differently."

Low-suffering procedures increase

The UK already has some of the strictest laws in the world on the use of animals in research. But its huge bioscience sector used more than 3.6 million animals in experiments in the UK in 2010, Home Office figures show.

This is the highest level in 24 years, although the Home Office says that the number carried out on species such as dogs, cats and rabbits fell, while the number of low-suffering procedures increased.

"There's more 3Rs research being done in the UK than has ever been done before and I don't think we've reached capacity by any means," Dr Prescott said.

An NC3Rs survey of 2,000 holders of Home Office licences to carry out animal research, published in 2008, certainly suggested that there was a long way to go.

Although there was a reasonable awareness of the three Rs, very few had actually applied for funding, Dr Prescott said.

"The reasons were that they weren't aware of funding schemes or didn't see them as relevant to their career aspirations, and didn't think they would be able to replace animals in their particular area," he said.

The centre has acted on the results of the survey, and Dr Prescott claimed that we would see a different picture today.

But the proposed new UK legislation in reaction to the European directive, an update to the 1986 Animal Scientific Procedures Act, will strive to promote better ways of sharing information on the techniques available.

According to its proposal, the government is considering carrying out frequent reviews to identify areas where animals could potentially be replaced, as well as expanding the role of the Animal Procedures Committee to run a database of alternatives that scientists could refer to when designing experiments.

Adrian Biddle, a postdoctoral research fellow at Queen Mary, University of London, and an NC3Rs Sainsbury fellow, said that although times are changing, scientists still come up against another brick wall: tradition.

'Mouse model' perception

"The problem at the moment is that there's a perception that to get into the big journals such as Nature and Science, you need a mouse model," he said.

His work uses cell-culture models to study the populations of tumour stem cells prone to growing and spreading, with the aim of finding therapies for the most drug-resistant.

"The belief continues that the only acceptable way of looking at human tumours is in an animal model, rather than being in a dish," he said.

"In the development of each drug, there are always going to be mice involved at some stage, but a large number can be avoided in the early stage."

Claire Richardson, a laboratory animal vet at the University of Newcastle and another NC3Rs Sainsbury fellowship winner, said that another point researchers must bear in mind is that refining experiments, rather than replacing animals, can greatly improve both science and animal welfare.

Her research, looking at fatigue in liver disease, involves implanting mice with transponders to monitor them at a distance, thereby replacing tests that can cause creatures stress and separate them from their social groups.

"Finding ways that are kinder to the animals and more accurate is better both for humans and for the lab animals," she said.

Funding struggles to keep pace

But while interest grows, funding for such research is struggling to keep up.

The NC3Rs has a modest annual budget of £5.5 million, and although this has risen from £500,000 at its inception in 2004, the body receives more applications than it can fund.

Meanwhile the Dr Hadwen Trust, a charity that funds investigation into replacing animals in research, has increased its investment in research from £222,000 to £720,000 in just three years, but was able to fund only seven of the 105 applications it received this year.

In September last year, the Nuffield Council on Bioethics also warned the government that it must step up its efforts to find alternatives to animal research, analysing the scientific barriers to replacing animals and setting targets for reducing the amount of animal research.

One thing that might encourage the government to invest is public pressure.

Dr Prescott said that although replacing animals in research is an area in which the UK leads the world, polls show that awareness of these efforts among the public remains relatively low and it might be worth shouting about more.

"About three-quarters of the public are supportive of animal research on certain conditions," he said.

"One is that it is for medical purposes, and the other is that there are no alternatives and no unnecessary suffering. That is the 3Rs, essentially."

elizabeth.gibney@tsleducation.com.