The Pharmaceutical Journal
Vol 268 No 7182 p88-89
26 January 2002

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What is the place of animals in medical research today? The debate continues

A recent campaign by the Research Defence Society has fuelled the debate about using animals in medical research. Is such a debate necessary? Or will it just inflame an already sensitive issue? Harriet Adcock investigates

Using animals in medical research is a controversial issue that some people feel strongly about. There are those who are vehemently opposed to animal experimentation and those who are convinced that using animals in medical research is essential.

It is fair to say that those opposed to animal experimentation have been more vocal than those who support it — we have all witnessed animal rights activists promoting their views on the high street.

In an ideal world medical researchers would be able to do their work without using animals and few would not support the principle that animals should only be used when there is no alternative. However, speaking up for animal research is something that many people are loath to do.

Last week, in an attempt to redress the balance, the Research Defence Society published a report — "The hope, the challenge, the people: perspectives on animal research" — in which those who conduct medical research and those who depend on medicine for their survival, share their views on animal experimentation. The report also highlights some of the medical milestones achieved through animal research (see Panel 1).

The people interviewed for the report, who include a teenage patient with cystic fibrosis, researchers, a veterinary surgeon and a general practitioner, are certain that using animals in research is necessary to overcome the diseases that still affect us. Their willingness to be interviewed and photographed for the report (although some names were changed) shows courage. Animal rights activists are passionate about their cause and there is a real threat of violence against those who openly support animal experimentation.

Indeed, the intimidation directed at the staff and shareholders of Huntingdon Life Sciences led the company to reconsider its future in the United Kingdom.

A spokesman for the Association of the British Pharmaceutical Industry said: "The irony is that if the protesters have their way, and stop animal research in the UK, it would lead to greater suffering for animals. The research would merely be done somewhere else, where the regulations might not be as stringent as they are here."

The stringency of the regulations is not, he says, a problem for the pharmaceutical industry in the UK and industry is happy to live with the safeguards. "We understand why they are necessary," he said. However, the physical bureaucracy of the system can sometimes be a problem.

Professor Colin Blakemore, Waynflete professor of physiology, Oxford University, has campaigned to promote open and constructive debate on the use of animals in medical research. He supports the UK's strict regulations but says that the bureaucracy makes it difficult to compete scientifically with other research groups. The introduction of the local Ethical Review Process in 1999 means that any proposed research requiring a licence has also to obtain ethical approval from a local ethical review committee. This has added to the length of time it takes to gain approval for research in the UK.

Widening the debate

In an interview published in the 2001 autumn issue of The Physiological Society Magazine, Professor Blakemore proposes that there should be a disclaimer at the bottom of every prescription, stating: "The treatment you are receiving was developed through the use of animals and was safety-tested on animals." This, he says, would remind patients of the role that animal testing plays in developing medicines.

Professor Clive Page, professor of pharmacology, King's College London, agrees that there should be a more open debate on the issue of animals in research. His interest lies in immunopharmacology — asthma, chronic obstructive pulmonary disease and bronchitis — and he conducts research using animals.

He explained why: "There are long-term changes [in asthma and COPD] that cannot really be modelled in people. The hallmark of asthma is that the airways are twitchy, that is, they respond to cold air and to things that are normally innocuous in healthy people. This tells us that there is something underlying the control of airways smooth muscle tone that is different in people with asthma. However, if you take the tissue out and study it in an organ bath, it responds normally. It is an in vivo phenomenon.

"Work has suggested that asthma is not just an inflammatory condition and that one of the things that regulates airway tone is airway nerves. We can study nerves in culture but we cannot really look at the integrated effect of nerves controlling muscle contraction, secretion of mucus, and all the other features we know characterise the disease, without looking at it in an in vivo situation."

Professor Page uses mice, guinea pigs and rabbits in his research. "You pick the species depending on the question you are trying to ask," he said. He explained that mice are used because they can be genetically altered so they lack genes encoding for specific proteins. They can also have genes, including those that encode for human proteins, put back into their DNA. This allows the researchers to use a hybrid — an experimental animal that incorporates human characteristics.

Rabbits are used, says Professor Page, because they are big enough to act as their own controls. This means that normal lung function can be measured in the same animal.

Professor Page has debated the use of animals in research widely and as a result has been targeted by animal rights activists. Asked why he is prepared to speak openly on the subject, he said: "Most of the problems in the world are due to poor communication, from personal relationships all the way up to wars. I think that the scientific and medical community, by and large, has assumed that because it knows what is going on, the public either also knows or does not need to know. My personal view, particularly where public funding is involved, is that the pubic has a right to know what is being done.

"Most people, at some time in their lives, have been prescribed a pharmaceutical, and nearly all of them will have no understanding of where medicines come from," he said.

Professor Page believes that all biomedical scientists should take responsibility for explaining this "whether it is the pharmacist when they dispense the medicine or the physician when they prescribe it".

Professor Page thinks the debate on whether animals should be used in medical research would disappear overnight if every time a GP prescribed a medicine they said: "Do you realise this has been tested on animals?" He also thinks that pharmacists could play their part, especially considering that the training they receive and the medicines they dispense are dependent on animal research.

However, he realises that intimidation by animal rights extremists means people do not want to talk. "The few of us who do, are seen as somewhat lunatic — this is not the case. We should all be doing it."

Professor Page believes that the issue deserves serious discussion. "In my experience, if you put [animal research] into context, most people understand the need to continue to do it."

This view is supported by a MORI survey published in May 2000. The survey, commissioned by the Medical Research Council, showed that most people in the UK are inclined to accept, in principle, the need for animal experimentation as long as it can be justified as being for medical research purposes. A report of the survey, which can be accessed via the MORI website (www.mori.com), says that scientists should be reassured that most people can approach the issue of animal experimentation in a sophisticated, rational way. It adds, however, that most of those who are inclined to support the use of animals in research have not firmly made up their mind, and most people notice the absence of balanced, reliable information.

The law relating to new medicines

A medicinal product can only be placed on the market in the UK once the developer has been granted either a national or European marketing authorisation. A mandatory part of the application (for a pharmaceutical product containing a new active substance) is the results of pharmacological and toxicological tests. The directive that governs this states: "If ... systematic absorption is demonstrated during therapeutic experimentation, toxicity tests shall be carried out on animals." It sets out the detailed requirements for testing, which must show:

• the potential toxicity of the product and any dangerous or undesirable effects that might occur under the proposed conditions of use in human beings
• the pharmacological properties of the product, in both qualitative and quantitative relationship to the proposed use of human beings

Experiments on animals carried out in the UK are subject to the provisions of the Animals (Scientific Procedures) Act 1986. Before issuing a licence for a project, the Home Office must be satisfied that the number of animals used and any distress or discomfort that might be caused are kept to a minimum.

Using alternatives

Some organisations are against the use of animals in any form of research. The British Union for the Abolition of Vivisection, opposes all animal experiments on ethical and scientific grounds. It believes that exposing animals to deliberate harm in a laboratory, for whatever reason, is morally unjustifiable. It argues, legitimately, that animal experiments tell us about animals, not people. "The results of animal studies can never guarantee the safety or efficacy of human medicines or other products," its literature says.

Both the ABPI and the Wellcome Trust, an organisation that funds medical research that uses animals, acknowledge this. However, they argue that using animals reduces the chance of developing unsuitable treatments and also enables research to be conducted that would otherwise be considered unethical. Many biochemical pathways are identical, or similar, in animals and humans and differences can often be accounted for.

Several organisations are working towards developing alternatives to using animals. Professor Bob Combes, scientific director, FRAME (Fund for the Replacement of Animals in Medical Experiments), says: "Over the past five years or so, there are two areas of research that have had an impact on the issue of using alternatives. First, computer modelling — the ability to represent [biological systems] graphically, to handle lots of information electronically, and to put previously acquired information into expert prediction systems. There have been great strides in this area." The second major area is the use of human cells and human tissue, which is itself a contentious issue.

Professor Combes explains that a number of tissue banks are being established around the world. "They allow tissue that is surplus to medical requirements to be made available to researchers." He added that methods were also being developed to keep tissues viable and cells differentiated. "Also, we now have the ability to grow cultures in fairly complex, tissue-like organisation. These are all great steps forward, but there are still limitations with models, whether animal- or cell culture-models.

"With all models, if you are interested in the effectiveness of a drug for humans, then you have to make an extrapolation. ... In the case of [animal] cell-culture not only do you have to do a species extrapolation but you also have to extrapolate from culture to whole organ."

FRAME's ultimate objective is the replacement of animals in medical research. "In the long-term, the ultimate solution to the problem of using animals in research, both ethically and scientifically, is to find alternatives. This might take many years but it has to be done carefully and scientifically."

Professor Combes acknowledges that the pharmaceutical industry has made great contributions to reducing the numbers of animals used in product development (see Panel 2). "An enormous amount of work is done before animal testing is considered," he said. High through-put screening has allowed batches of molecules to be assessed and potentially toxic molecules discarded from the development process before having to be tested on animals.

The number of animals is also being reduced by the harmonisation of regulatory requirements worldwide. In addition, there are now a number of non-animal tests that have now been accepted for regulatory toxicity testing.

This trend to reduce the number of animals used in medical research should be welcomed. The past couple of years have seen a slight rise in numbers, mainly because of the use of transgenic animals in research. Undoubtedly, this area of research will bring great benefits in improving health but it is important that scientists continue to question the necessity for using animals in their research.