Some facts about Parkinson's and Alzheimer's research

15 August 2011

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Category: Antivivisection & extremism

monkey–primate–cover.jpgThe animal rights group Animal Aid launched an ill-informed, illogical and ill-conceived campaign against medical research charities a few weeks ago. Two of our neuroscientist members have felt compelled to write a counter, below, to some claims in the group’s publication Victims of Science.

Animal Aid planned a 'Day of Action' on Saturday 13 August, and we have seen some of their posters around London. However, we are pleased to report little evidence of any activity.

History of Alzheimer's disease research

While it is certainly true that some findings regarding Alzheimer's disease are made in humans, it is also the case that many more discoveries, particularly regarding the biological mechanisms, are made in animal models. Furthermore, the ability to investigate the human brain at the genetic and molecular level has been made possible primarily because of tests that have been developed using tissue from animals.

Predictive value

The authors appear not to understand the fundamentals of science. Of course experimental Alzheimer's disease, which is modelled in animals, cannot be exactly the same as the human condition, since researchers are working with animals, not humans. Since it is, however, unsafe to conduct drugs studies in humans without as much evidence as possible that the compounds are safe, researchers combine a host of techniques, including computer modelling, in vitro cell culture assays and in vivo tests, to determine as much as possible that every medicine is safe before it is given to an Alzheimer's patient.

It is true that some rodent models of Alzheimer's disease only depict certain aspects of the disorder, while other models mimic several/most aspects of the disease. But modelling a specific aspect of the disease is extremely valuable because it allows scientists to understand sole influence of that biological alteration on molecular function, cellular function and behaviour. The models depicting multiple aspects of the disease are equally valuable because they allow researchers to study the interaction between different aspects of the disease pathology.

Animal memory tests

Researchers work to very strict Home Office regulations that ensure the animals are never 'starved' and the tests are not 'cruel'. If this were to happen, the scientist would lose his/her licence to work in the field and the laboratory would lose its licence too. Home Office inspections of the laboratory occur regularly and without prior warning.

Many more behavioural tests are available to researchers than the few listed by Animal Aid. While some tests are deliberately simple and only address a very specific aspect of behaviour, very high level processes have also been studied with great success. Using operant chambers, experimenters can teach an animal to perform certain actions (like pressing a lever) in response to specific stimuli, like a light or sound signal, by delivering rewards. We can study high-level brain processes in this way, ranging from different types of memory function to cognitive flexibility and rule learning. Since the apparatus is computer controlled, it can measure movements to fractions of a second and avoids experimenter bias.

Animal models in developing Alzheimer's treatments

For as long as there is no cure for Alzheimer’s disease, people against research with animals will claim that this area of study has been a failure. This does, however, completely disregard all data that have been gathered about Alzheimer's disease using animals. Greater understanding of genetic influence and protein alterations has driven many aspects of research and opened up hundreds of new avenues for exploration.

Do animals suffer in Alzheimer's research?

The claims in Victims of Charity are distorted. For example, in the Morris water maze the water is not cold and mice would never ever be in danger of exhaustion and drowning. Researchers and laboratories adhere to strict Home Office regulations and are regularly inspected without notice. Failure to comply would mean loss of licence for both the scientist and the research laboratory. The use of 'extremely cruel methods' is not allowed within Home Office regulations.

Animal testing and therapies for Parkinson's disease

The most commonly used drug in the treatment of Parkinson's disease is L-DOPA. Animal Aid claims that this and the other treatments mentioned in its report were developed without the use of animal testing. This is symptomatic of a limited knowledge of the history of medicines; animal testing of L-DOPA led to a Nobel prize.

Animal Aid claims that L-DOPA was developed in the 1960s by Oleh Hornykiewicz without the use of animal testing. In fact it was described much earlier by Arvid Carlsson. In 1957, Carlsson published an article where he showed that mice and rabbits, made immobile following an injection of a drug that stopped the transport of dopamine (the chemical which is decreased in Parkinson's disease), were able to move again following administration of L-DOPA. It was based on this groundbreaking work – for which Arvid Carlsson won the Nobel price – that clinical trials with L-DOPA began.

The history of L-DOPA is similar to that of other medicines/treatments in that it was developed using animal research and only introduced to human trials once it had been shown to be safe enough and effective in treating the symptoms of the disease in animals. This use of animals in safety testing is necessary for legal as well as ethical reasons. Most would agree that patients should not be given medicines unless doctors are confident that they are safe and effective.

Efficacy testing

The Animal Aid report also contains misunderstandings regarding the different tests that are used as part of preclinical research. The report refers to a study conducted at a US university and lists a range of tests the researchers conducted which in Animal Aid’s opinion constitute as 'manifestly cruel tests'. Disregarding the fact that the study was not conducted in the UK, and is not directly applicable to a debate on the ethics of animal testing in Britain, the authors appear to have not fully understood the nature of the tests. An example is the description of how mice are 'made to walk on balance beams' as inhumane.

The balance beam test

This is frequently used, one of the reasons for its popularity being that it is non-invasive and does not cause any harm to the animals. The test involves mice and rats voluntarily walking across a ledged beam in order to enter a dark box at end of the beam, where there is a reward, for example sucrose pellets, awaiting them. This draws on the animals' natural behaviours, as rats and mice in the wild are very good at climbing and balancing and will do so as part of their daily foraging behaviour. The beam the animals walk across becomes narrower the closer to the end the animals come, causing animals with poor balance to either make occasional foot slips at the narrower end, or resort to walking on the ledge rather than the beam.

The choice to walk on the ledge rather than the beam, the number of foot slips made, and the place on the balance beam where the foot slips occurred may then be used as a measurement of balance. However, thanks to the design of the balance beam, the ledge which is attached to both sides of it stops animals with poor balance from ever falling off the beam. Even if researchers did not use the ledge, which is very uncommon, there are Home Office regulations regarding how close to the floor the beam must be, and a requirement for padding underneath it to prevent the possibility of animals hurting themselves. The balance beam test is thus an efficient way of measuring the balance of animals engaging in what is for them a natural behaviour, without risking them any physical harm. It is similar to most other tests of motor function in that it is designed to draw on natural behaviours in order to prevent unnecessary stress and discomfort.

Animal models for Parkinson’s disease

In Animal Aid’s opinion, the animal models of Parkinson's disease are not complex enough to enable proper study of the disease. It fails to appreciate that there is a large variability in the way Parkinson's disease isexpressed in human patients – making it impossible to create a 'one size fits all' animal model of the disease. Instead, individual hallmarks of Parkinson's disease are identified in human studies and these are then researched in animal models. This enables researchers to understand which of the many abnormalities occurring in a brain with Parkinson's disease can be targeted with treatments to give maximum relief of symptoms. 

Read more

AnimalResearch.info page on Alzheimer's disease

AnimalResearch.info page on Parkinson's disease

Medical Advances and Animal Research p11