Case study: Dr David Priestman

Research: Trying to understand and perhaps eventually treat a very severe and disabling disease which leads to an early death.

Animals used: mice

Dr David Priestman: ‘I work on a disease that affects a small number of people, but which is devastating. It’s basically a severe epilepsy syndrome with blindness, and affects children from shortly after birth. The children can do very little: they never learn to walk or talk, they can’t hold things, they have to be fed by a tube, and they’re blind; it’s absolutely devastating. But they may survive into their 20s.

‘The only known cases so far belong to the Amish community in the USA, and the condition doesn’t even have a common name yet. The disease, which runs in families, is all to do with compounds called gangliosides, a type of molecule that is important for the brain and nervous system. Due to a specific genetic defect, the people affected can’t produce gangliosides and this has the devastating effects on their brain and central nervous system that I’ve described.

‘There is a mouse model with the same genetic defect as people with the disease. In other words, transgenic mice (mice with a specific genetic alteration) have been created that, like the humans, also lack the gene for producing gangliosides.

‘The interesting thing is that the mice, unlike the humans, are totally fine. There’s nothing wrong with them. That is actually very helpful, because if we can find out how the mouse escapes the disease, we can try and use that as way of treating the human patients.

‘From our research so far, it seems that the mouse manages to produce a different class of gangliosides that humans don’t, which can replace those that would otherwise be missing. The mouse has another ‘pathway’ for producing gangliosides which is an alternative to the pathway controlled by the defective gene. Humans also have this pathway, but it’s not activated. If we could activate it in humans it might be a way of treating them. That is what we are working on.

‘In terms of how we use animals, our experimental mice don’t actually have anything “done” to them. We breed them, they live normal lives, and then we put them to sleep – humanely, of course – at different intervals. After death we remove blood and tissues for analysis such as biochemistry, histology, pathology, and electronmicroscopy. Side by side with the animal work we’re doing, we’re getting clinical samples from human patients biopsies, blood samples and so on - and doing similar sorts of analysis. By doing that we can see what’s going on at a cellular level. It’s through this combination that we’ve been able to establish this different pathway in the mouse that doesn’t appear to be activated in the human, and which could be the route to a treatment.

‘One criticism you sometimes hear about research using animals is that there are differences between humans and animals. Some people wrongly claim that because of these differences animal research is no use. That’s incorrect on two counts. First, there are far more similarities than differences between mice and humans, so in many cases the mouse model replicates the human disease very closely. Second, even where there is a difference, it can also be extremely useful. In the case of my current research, the difference provides very important insights into the precise role of gangliosides in the brain and why their loss causes the human disease.

‘The mice I work with are housed in the Biomedical Sciences Building and I go there regularly for that part of my research. The previous building I worked in was fine, but it was decades old. The newer, purpose-built facility provides even better conditions for our experimental animals. It is much better for all concerned – animals and researchers – when the animals are in one centralised, state-of-the-art facility. The better the standard of the building, the better the welfare of the animals, and the better the science.

‘I’ve always been happy to speak about the animal element of my work. All the work I’ve done has been very closely related to human disease, and the human work and the animal work has always gone hand in hand. I know that what I do is of clinical importance: over my career I’ve seen first-hand how animal research translates directly to making things better for humans.’