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Use of animal models in biomedical research

People often ask how the use of animals in experiments can be justified when animals are clearly so different from humans. The answer is that animals are used in specific areas of research where they do not differ from humans for the characteritics being studied, and where the differences are of no significance to the project. Animals are therefore used as highly specific 'models' of humans.

Models should resemble the thing being modelled, but must be different in other ways

The similarities and differences between models must be considered in every project. The important features of a model can be seen using an analogy: a doll is a model of a human used to entertain a child. To be a useful model for this purpose it needs to be like a human in some respects, such as having characteristics that a child recognises as a head, a body, eyes, nose, limbs etc. However, it is different from a human in many other respects. If it were to be more human, and have a nervous system so that it feels pain, and blood so that it bleeds when damaged then it would be a worse model for its particular purpose. We would not want blood on the carpet or the ethical dilema of causing pain.

A model must therefore be like the thing being modelled in some respects, and unlike it in some other respects, with some characteristics being neutral. Models are also specific for a particular purpose. We cannot do medical reserch using dolls, and similarly a rat may be suitable for some research projects and not for others.

Models can be "better" than the thing being modelled

Humans have certain cognative abilities such as addition, subtraction, multiplication and division which can be modelled using an electronic calculator. This sort of model can be called a "super model" because it performs a specific task better than the thing being modelled. Given the choice between using our brain to multiply a two three digit numbers or the calculator, most of us will choose the latter. The calculator is a highly abstract model of a very specific human function, and is only of value for one specific purpose.

In some cases animal models and in-vitro models are super-models of humans, because if humans were available for the experiment we would choose not to use them. For example, if we want to study some aspects of genetics we may choose a computer model, a fruit fly or a mouse. We know enough about genetics to be reasonably sure that the results can be applied to humans, but our models are able to give results quickly and cheaply.

The similarities and differences between animals and humans are taken into account when choosing a model

In trying to assess the validity of animal experiments it does not make sense to compile lists of differences between animals and humans, because we want them to be different in many ways. When studing obesity a mouse strain might be a good model of humans because it becomes obese, gets diabetes and dies young. The same strain may be useless in a long-term toxicity study for exactly the same reasons. Each research project must give careful consideration to the choice of the specific model.

An example: a model for the treatment of colon cancer

Colon cancer can usually be treated effectively unless it has already spread to the liver. By the time it is diagnosed this may have already happened, and by this stage it could be inoperable. In this example, however, a new microwave probe, about the size of a pencil, has been developed. This could be inserted into tumours, allowing a dose of microwaves to be applied, cooking the tumour and killing it.

The problem was to decide the dose (volts) and time required to cook a liver tumor of a given size with this probe. The experiments also needed to determine whether several tumours could be treated in one patient, and what happened to an individual with some liver / tumor tissue killed in this way. Would it kill the patient? Clearly it would be both unethical and impractical to use a human for these studies, even when terminally ill patients are available, so an animal model was needed.

As the probe could not be scaled down, the animal model needed to have a liver of about the same size as a human. Rats were clearly unsuitable, but pigs were a more appropriate choice. The pigs were anaesthetised, and one or two areas of the liver treated with various doses of microwaves. After being allowed to recover the pigs were then killed at different time-points.

This research showed the dose of microwaves which is predicited to kill pig liver tissue of various diameters. The pigs were found to tolerate several lesions, and after two months the lesions had shrunk, although the animals were not kept long enough to discover whether they disappeared.

Clinical trials ensure that the model has worked successfully

There is no absolute assurance that the animal tests accurately predict human responses. As this was pig, not human, liver and it was normal tissue, not a tumour, it is still necessary to do a small clinical trial before widespread use. If the prediction had been inaccurate, then the first human patients would suffer. Fortunately, the pig data was highly predictive of the human results, and several terminally ill patients have now be successfully treated and have left hospital apparently fully recovered.

With the development of new drugs the clinical trial is time-consuming and expensive. With this simple surgical model there were some terminal cancer patients who it was estimated only had a few weeks to live, but were able and willing to give informed consent. In this example it did not matter that the pig differs from humans in many ways so long as the liver was about the same size as the human liver, and it responds in a similar way to microwaves.

Alternatives that replace the use of animals are also used as models

Most of the replacement alternatives to the use of animals are models of the same sort. They resemble some very specific human features, but differ in many other ways. As an example, in early human pregnancy there is a surge of hormones affecting the uterus. Many years ago pregnancy was diagnosed using an animal model. A sample of urine was injected into some mice and the increase in uterus weight measured, or into frogs which then ovulated if the woman was pregnant. Now this can be modelled in a home pregnancy testing kit.

Last edited: 27 August 2014 06:00

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