In our research labs we use genetically altered animals, usually mice, to test scientific theories which we hope will one day lead to new medicines and treatments. In terms of my own work, we create mice with trisomy, which means they have an extra copy of a certain chromosome. In humans, trisomy 21, otherwise known as Down syndrome, is probably the most well-known of these conditions.
The goal is to find ways of alleviating the symptoms of these conditions. We look at how trisomy changes neurological mechanisms and how it influences embryonic development, stem cells, and the programming and function of cells. We identify and target these mechanisms and hope to treat them through therapeutic drugs. These mechanisms are often similar to those affecting humans with comparable conditions.
We can hope to heal humans thanks to the mouse model. Ten years ago there were no real prospects for treating Down syndrome. Today, Roche is testing a new drug to reduce its symptoms, including problems with learning, memory and speech. Other drugs are on their way. Ten years of research mean that we now have several promising leads for treating Down syndrome.
The animals we use also allow us to do research on rare and very rare genetic conditions, those affecting as little as 1 in every 10,000 people. These include 17q21.31 and 16p11.2, two syndromes where a part of a chromosome is “deleted,” and ring chromosome 14, which results in difficult-to-treat epilepsy. The rarity of these conditions means that it can be difficult for doctors to know even what the typical symptoms and their intensity are. The animal experiments can help us determine what is representative and how these symptoms can be treated.
The Three R’s
We take very seriously our efforts to reduce as much as possible the degree of suffering and loss of life among our animals. We have mandatory training on animal handling and well-being before being allowed to work with them and this continues with “on the ground” training as we specialise.
In our work we follow the principles of reduction, refinement, and replacement. By reduction we mean that we follow tightly optimised procedures to reduce the number of animals we need to use. For example, we know exactly how many animals we need to detect a 20% difference between a test population and a “normal” reference population.
By refine we mean making the animals’ lives as positive as possible. This means we emphasise non-invasive methods of experimentation and, when needed, we use anaesthetics and analgesics to reduce any pain felt. In terms of mutations, our animals do not undergo anything that doesn’t occur in nature. Human children with these genetic features are born naturally. If ever there are animals with very serious problems we can put them down (which I have not yet had to do).
Finally we try to replace animals where possible with other means, such as growing and experimenting with cells in Petri dishes. However, this is typically not useful for studying mental disabilities due to Down syndrome, such as long-term memorisation, interaction with space and objects, social recognition, thinking, and senses. For this cell cultures are no substitute. But we are “thrifty,” so to speak, in all we do, including our use of animals. We have to be very careful in how we keep and treat them. In Europe, and certainly in France where I work, the use of animals is very well regulated [hyperlink to French regulation].
There are some who say we don’t need animal testing anymore. But for the kind of research we do, there’s very little that can be achieved with cells in Petri dishes. We do it knowing that people will benefit. In the 1920s, research using dogs and bovines led to knowledge of insulin’s role in diabetes and to the creation of medical treatments (including for animals with diabetes). Today there are still countless diseases which we could treat better. We work knowing that in the end our research will help heal people and improve their lives.