Open Eye: On the track of the fatal protein Research into Alzheimer's and CJD has earned a rare distinction. Yvonne Cook reports

Click to follow
Bound in two volumes between plain black covers is Dr Harry Baker's life's work. It looks unspectacular - but the research it contains has just won him the rare honour of a DSc (Doctor of Science) degree from the Open University - the first OU graduate ever to receive this distinction.

His research findings embrace two of the most distressing and dreaded diseases of our age - Creutzfeldt-Jakob Disease(CJD), the human counterpart of the so-called 'mad cow disease' BSE, and Alzheimer's.

For more than 20 years he and his co-researcher Dr Ros Ridley - a behavioural psychologist who also happens to be his wife - have been working for the Medical Research Council to advance our understanding of what goes wrong in the brains of people suffering from dementia.

His mother was a canteen supervisor and his father a patissier - and Harry turned down a university place at 18 because there was no family tradition of going to university.

He began his career as a biochemist studying the structure of muscle proteins, then moved on to looking at the behavioural effects of drug treatments for psychosis and dementia.

Becoming increasingly interested in behaviour he joined the OU to study psychology, and gained his first degree in 1982.

Dementia is not a pleasant subject, but it's one many of us are destined to experience, directly or indirectly through elderly friends and relatives. As the population of the western world ages, age-related dementia is becoming increasingly common.

"There are many different kinds of dementia, of which Alzheimer's is the most common. At 65, about five percent of people will be showing signs of moderate to severe dementia." says Harry. "By the age of 80, it will be around 20 percent."

The symptoms are caused by characteristic changes in the brain tissue which are plainly visible at post mortem, but the underlying cause of most forms of dementia remains a mystery - except that it is almost always associated with ageing. The good news is that Harry's research appears to be pointing towards a new and better form of treatment for Alzheimer's.

It has been known for some time that symptoms of Alzheimer's are connected with changes in some of the neurotransmitter systems -the brain's 'information highways' - in particular one called acetylcholine.

Research by, among others, the OU's Brain Research Group led by Professor Steven Rose, has shown that when the brain is low in acetylcholine, the ability to learn and remember is reduced.

But drugs aimed at boosting the acetylcholine system in Alzheimer's patients have met with limited success - improvements are short lived, and there are significant side effects.

Harry and his team decided to approach the problem from a different angle. "We thought that we would try to reduce the inhibitory system to match the reduction in acetylcholine, using drugs which slow down the inhibitory pathways. So far, it appears to be working."

Such treatment is unlikely to be of help in advanced cases, but it may be able to slow down the onset of symptoms in the earlier stages of Alzheimer's: "Basically, we would hope to be able to keep people operating on a better level for longer."

But he stresses it is not a cure. "The prospects for a cure are not good at the moment. We need to understand a whole lot more about the mechanism."

The same is true of that other scourge of our times, CJD, which Harry and Ros have been studying CJD since 1979 - long before 'mad cow disease' was ever heard of.

They were the first to demonstrate that, uniquely, CJD can be both inherited, and transmitted.

In a collaborative study with Nobel Prize winner Stanley Prusiner, who discovered the prion protein responsible for effects of CJD, Harry and his colleagues travelled Britain taking blood samples from members of the same family with a history of the disease.

As a result it was possible to pinpoint the genetic mutation responsible and all members of the family were given the option of genetic testing which would reveal whether or not they had inherited the CJD gene. Further research by Harry and other scientists has now uncovered around 25 different forms of CJD, some inherited, but most apparently occurring at random. When in 1996 the first suspected cases of BSE-related dementia were announced, evidence from Harry's earlier research contributed to the realisation that it was in fact a new form of CJD, now known as 'new variant CJD'.

Harry had also been working since 1986 on the transmission of BSE from cattle, demonstrating that it was possible, in theory, to transmit the disease to primates.

Although it has not been proved conclusively, he feels the evidence of the link between new variant CJD and BSE is strong. His work has formed part of the evidence put before the ongoing BSE inquiry.

Harry is reassuring on one point: "I do believe the measures the government has now put in place are the right ones - you are probably safer eating British beef now than any other."

What he's not able to answer is how many people who ate contaminated products in the late 1980s and early '90s may be incubating the disease: "On our present understanding, it could be anything from a handful to millions. Anyone who tells you anything different, doesn't know what they're talking about."

One clue to the likely pattern of any future epidemic is that about half the population is probably more susceptible to it than the other half, for genetic reasons. Those interested in the full BSE story can follow it in Harry's latest book, Fatal Protein, recently published by Oxford University Press.

Spending more than 20 years studying diseased brains has by no means dampened Harry's enthusiasm for his subject. "I don't find it depressing - what would be depressing was if I wasn't able to do my research. Our understanding of dementia has increased enormously over the last 20 years."

He and his wife remain in touch with members of the family with whom he did his original research into hereditary CJD, and have formed a close friendship with them.

"I am constantly aware that behind all of it are patients. The diseases we are investigating cause a great deal of anguish to the sufferer and their families."

Higher doctorates

A Doctor of Science (DSc) degree is awarded for a consistent scientific output over many years by a person having a substantial reputation in their field. There have been only eight higher doctorates awarded by the OU in its entire history, and Harry is the first OU graduate to receive one. More information about doing research degrees of all kinds with the OU is available on the Web: at www.open.ac.uk go to: /OU/ResearchDegrees/Prospectus

You can also request a prospectus from 01908 653232 or ces-gen@open.ac.uk

Comments