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Last Updated: Monday, 24 July 2006, 13:17 GMT 14:17 UK
Case studies: The three Rs
Some researchers are working on ways to lower the numbers of animals used in scientific experiments.

Using computers to create virtual cells, tissues and whole organs, growing these components in the laboratory, or using new scanning techniques to peer inside the body are some of the methods being used to edge closer to the animal-free laboratory.

Here, three scientists talk about their research which is helping to reduce animal experimentation.

COMPUTER MODELLING

Professor Denis Noble is based at Oxford University, and, with his team, was responsible for creating the first virtual heart.

Heart model (Denis Noble)
The model can mimic a heart attack

I started working on this 46 years ago, at the very beginnings of biological computation.

The breakthrough came when we collaborated with another group that had computer simulated the anatomy of the whole heart.

They had created their software in a way that made it possible to "pour" our equations for cellular activity into their whole organ model.

In essence, we could jump to another level of analysis - not just cells but the whole organ.

Indeed, on a screen you can see a beating heart, you can see arrhythmia and fibrillation; you can reproduce all of the electrical changes that kill people.

We can use the virtual heart to distinguish whether a drug is likely to produce arrhythmia or if it is likely to be a good compound.

It has become so refined at the cellular level that we are used by the drug companies to work out the interactions of some of their new drugs.

Currently, we are working with high-performance computer teams to bring whole organ simulation down to realistic times.

Because hundreds of millions of differential equations are simultaneously being solved, it may take 30 hours just to do a few beats of the heart.

I would say the real benefit of the model is that it can do a preliminary filter of your compounds, and that can replace some of the very early stages in animal experimentation.

IN VITRO

Dr Phil Stephens is a cell biologist at Cardiff University. He is developing an in vitro system to screen treatments for diabetic ulcers.

Leg ulcer cells (Phil Stephens)
The genes fluoresce green

Our interest is in chronic venous leg ulcers and diabetic foot ulcers in the aged.

Diabetes is on the increase, and as a result about 15-20% of diabetics will get a chronic non-healing wound. Some of these wounds can last for many years and they have a huge impact on the patients' quality of life.

We have to get these wounds to heal.

There are a number of different animal models out there, but they are not really good models for these wounds.

So, we began developing an in vitro system.

Basically, we have taken cells from these diabetic wounds and we are growing them in the lab.

We are looking for the genes that are expressed by these cells, trying to find the differences between normal and diseased cells.

Once we have found the diseased genes, we link them to fluorescent reporters, so every time a cell expresses the particular gene it will light up.

The idea is that we can monitor when the disease genes are being switched on and off.

So somebody can come along with their drug they have developed, and they can put it onto the cells.

If it up-regulates the disease gene, perhaps it is not worth taking forward; if it down-regulates, maybe we should go forward with that one.

The in vitro system is not going to replace the animal models, but it will enable a vast number of pre-screens to be undertaken, hopefully vastly reducing the number of animal experiments that go on.

IMAGING

Professor Chris Higgins is director of the Medical Research Council Clinical Sciences Centre and is involved with imaging work to try to further understanding of obesity.

MRI scan of a mouse (CSC)
MRI enables the team to look inside of the mice

The main thrust of the work is trying to understand the genetic and environmental factors that determine obesity.

Why do some people become obese, while others stay thin? Why is it that some overweight people readily develop diseases like type 2 diabetes, while others do not?

There are clearly genetic and environmental factors that determine this, relating to the level of fat inside the body, where it is, and how this modulates glucose utilisation in the body.

Much of this research can be carried out in the clinic. We can image subjects using magnetic resonance imaging (MRI), allowing us to look inside their bodies at the amount, distribution, position and function of the fat.

But the one thing that is difficult to do is to understand the genetic and the underlying molecular basis of obesity, and for this we need to use animals, mainly mice, if we are going to develop more effective therapies.

One area we are looking at is what controls appetite and satiety.

To do this in the traditional way, we would have to dissect the animal brain, but to avoid this we use in vivo imaging to look at the areas of the brain related to hunger and satiety.

The beauty of imaging is that it also allows us to investigate the same animals over and over again. So, instead of using hundreds of animals for one experiment, we would now require maybe six.

We can also follow them throughout their lives, and it allows us to translate the work from the bench to the clinic much more quickly and effectively.




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