Dr. Richard Fosse

The 3Rs: what is progress?

Richard Fosse February 21st, 2012 1 Comment

Advances in science will present some people with new dilemmas. What if new research methods mean more primate-based studies but using fewer animals overall?

The latest trends in biopharmaceuticals will make it possible to develop fragments of antibodies – some of which can be used as new therapies – without using as many mice or rats as would have been required in the past.

The early stages of research can be done using large volumes of cell samples and with the help of computer modelling, so we essentially skip the animal-intensive phase of early research where large numbers of potential therapies would previously have been tested on rodents.

Now we are moving into an era where we will find ourselves with a smaller number of candidates – let’s call them ‘could be’ therapies – which are ready for the next stage.

However, these antibodies are so highly specific to primates, the group to which we as humans belong, that testing in rodents is less likely to be succesful. Trying out new biological therapies in humans is a non-runner: some will not work; others could have serious side effects. The upshot is more primate research.

If we carry out studies using, for example, dozens more monkeys but it means thousands of fewer mice are needed, will this be more or less controversial?

Refining research methods

All of this brings me to the question of how we define progress in animal testing. In Europe, the focus has been squarely on the 3Rs – reduction, refinement and replacement.

There is, in my view, a particular emphasis on replacement. But rather than look exclusively at the absolute number of animals involved, we should consider the methods being used and the quality of science being produced.

‘Refinement’ is in danger of becoming the forgotten ‘R’. The total number of animals being used in Europe has been more or less constant in recent years but investment in science has increased and the output has also risen.

So research activity has actually increased without a major leap in the use of animals. To me, this is progress, but if you look only at the total number of animals used in research, it looks like we’re going nowhere fast.

Transgenic and humanised animals

Other developments in animal research – like the ability to breed transgenic animals in order to design highly specific experiments – have also had an impact on the quality of science. We have also been able to create mice that accept an exchange of their mouse blood with human blood, thereby creating an animal that is able to be infected with parasites that only infect human beings.

For example, it was once feared that studying how the parasite which causes malaria affects humans would not be possible using animal models. However, humanised mice allow us to do things never thought possible. These mice allow us to test new drugs that are targeted to the very parasite that causes such havoc in humans in many parts of the world.

Good news? For me, the answer is yes as it opens the door to a deeper understanding of malaria.

Others dislike the idea of creating transgenic or mutant animals because they see it as unnatural. Indeed it is. But if it’s natural to die from a mosquito bite then most will agree that ‘unnatural’ interventions are morally acceptable – if not imperative.


A new era

My point is that science is moving towards an era which will force us to confront difficult questions.

  • Will we accept more primate research if it reduces the use of large numbers of rodents?
  • How should we view the huge growth in transgenic and other modified animals given the potential benefits for animals and humans?

Philosophical debates, like science, often presents us with complex equations; equations which perhaps cannot be solved by reliance on simplistic interpretations of the 3Rs.

We ought to focus on the quality of our animal science rather than zeroing in on the quantity alone.

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