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New research funds must not be wasted
Posted 29 March 2012
The Government has this week announced that research funding into dementia is to be doubled by 2015. This is potentially very good news, but there is a real risk of these precious funds being squandered.
A Professor who taught me what used to be called “geriatric medicine” once likened the life of dementia sufferers to a house of cards. A temporary stability exists, but when just a single component is removed, the whole edifice tumbles down. Many times in my medical career, it has felt like I’ve been present shortly after this horrible moment, when a simple pneumonia or the loss of a valued carer becomes catastrophic. In the Emergency Department, we are often struck by the malign and dangerous interplay of cognitive decline and physical illness. We know sufferers would recover more effectively in a supportive home environment, be that with relatives or carers. Sadly, many end up being admitted to hospital due to a breakdown of their often fragile community networks.
Cameron’s ‘quiet crisis’ has been out there for some time, and continues to unfold. The news that the government will increase funding for dementia research is therefore most welcome. It is right to insist, however, that this boost is spent wisely. To date, research into new treatments, especially for Alzheimer's, has been notable for an extraordinarily high rate of attrition. A large and growing list of highly costly treatment failures has disheartened sufferers and their carers, who have become used to hype transmuting once more into disillusion.
The Government’s funding windfall must not be allowed to be frittered away on further unproductive laboratory research – we do not need yet another bunch of expensive and time-consuming flops. Much of the blame for this debacle lies in the use of primitive ‘animal models’ of dementia, and the extrapolation of facile animal memory tests to human patients.
The experimental Alzheimer's Disease that researchers produce in animals is emphatically not the same as the human variety. Although some aged primates and dogs develop a disease with some similarities, no animal species suffers from the same condition. Thus, researchers have had to produce laboratory facsimiles, with what their creators admit have been partial and unpredictable results. Their methods have included injection of neurotoxins directly into the brains of rodents and primates, and poisoning rabbits with a diet of cholesterol and copper. However, by far the most popular ‘models’ of recent years have been transgenic mice, whose genetic make-up has been altered.
The tests used to assess candidate drugs in these mice have always been crude and reductionist. They include the ‘active avoidance task’, described as ‘a fear-motivated test based on electric current as a source of punishment’. A variety of mazes are used, to force often food-deprived rodents to make directional choices. In ‘isolation-induced aggression testing’, mice are set to attack each other, after being held in solitary confinement for prolonged periods. One of the most widely used tests is the infamous Morris water maze, which compels rodents to swim around a pool of water in order to find an escape route. Apart from being manifestly cruel (mice are scared of being in water), the procedure is highly operator-dependent with myriad variables.
It is no wonder that these techniques have been instrumental in developing a whole range of ineffective drugs for Alzheimer's. Time and time again, drugs that seemed powerfully effective in mouse mock-ups have failed in clinical trials. Experimental animals, however, are not necessarily chosen for their value in predicting human outcomes – the selection is often made on grounds of convenience and tradition. Mice, for example, breed prolifically, are relatively cheap to maintain, and don’t live long. Such expediency should not feature in the allocation of these new funds. In common with many other areas of public spending, research projects should be supported only if they have a good chance of delivering concrete benefits for patients.
In our search for ‘cures’, we must also remain aware that a huge burden of unmet need revolves around non-medical issues. We should be aiming to be a world leader in the care and compassion we afford to dementia sufferers, not just in the number of published papers, citations, or research posts. Enough money has been wasted already on misleading animal experiments – hopefully the same mistakes will not be repeated.
Dr Adrian Stallwood is a Specialty Doctor in Emergency Medicine in west Wales, and a Clinical Teacher of medical undergraduates from Cardiff University. He is also Scientific Consultant to Animal Aid.