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ONE day, scientists say, they might run out of problems to solve — much as the explorers ran out of continents to discover — but that day is a distant prospect for neuroscientists. If science is exploration, then the brain is the final frontier — and explaining brain disease, as a concept, remains a great impasse.

"People have a real problem with this idea of brain disease and brain failure," says renowned neurobiologist Malcolm Horne, deputy director of Melbourne's Howard Florey Institute, where scientists are seeking cures for diseases that affect more than 3 million Australians.

As complex as the brain is, Professor Horne says, to neurobiologists the differences between brain diseases are subtle.
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"The difference between epilepsy and multiple sclerosis and schizophrenia and addiction and Parkinson's disease may not be nearly as great as the community thinks. And the difference between motor neuron disease and Alzheimer's disease is probably fairly subtle. It just happens to be that it picks on a different set of nerve cells."

Professor Horne says scientists have not yet explained this well enough to the public, but the gulf in understanding may also be due to the fact that dramatic strides in brain research are "pretty new".

Neuroscience has lagged behind the other sciences, he says, because it has lacked the tools needed to understand how the brain functions "as a network". This, he adds, is the most distant part of the knowledge frontier.

With that in mind, the Florey recently joined with the Brain Research Institute and the National Stroke Research Institute to form the largest hub of brain research in the southern hemisphere, the Florey Neuroscience Institutes.

Its aim is to become one of the world's top 10 neuroscience centres, bringing together up to 700 research and support staff on two new campuses at Parkville and Heidelberg. Construction is under way — at an estimated cost of $204 million — and due to be completed next year. Its ambitious plan is to attract the best brains to Melbourne, to take research discoveries to the next stage of clinical trials and to develop better treatments.

Finding better ways to explain brain disorders to the public is a priority, too, Professor Horne says.

Compare brain disease with heart disease, he says. Australia has a Heart Foundation, and experts don't need to explain the finer points to the public: "It's heart disease and people understand that." The same goes for kidney disease, with the Kidney Foundation. "People just understand there's kidney disease and kidney failure."

Not so for "brain disease". People can't see it in the same singular way.

"So we have the Alzheimer's Foundation and the Epilepsy Foundation and the Fragile X Foundation, on and on and on it goes," he says. "And this becomes a real problem for speaking with the community about what brain disease is."

He also concedes there is a more fundamental, controversial debate about the nature of neurobiology, given its underpinning notion that the essence of being human lies in the way the brain functions.

Professor Horne, who described himself in a recent journal as "a card-carrying biologist", says humans are stalked by dualism, the philosophy of the relationship between mind and matter, which begins with the claim that mental phenomena are, in some respects, non-physical.

"Psychiatry and the brain and the mind are really, to biologists, one and the same thing," he says. "Therefore, depression and the affective disorders are really, in many ways, disorders of the brain."

Many biologists view addiction as a disease in basically the same way they do Parkinson's and Alzheimer's — "a hard thing to explain to people," he admits. So while he admires psychiatrists, he sees them as "stuck with philosophy — until you can do it to have a testable hypothesis. And then you can do science."

It's a contested view. French sociologist Bruno Latour's renowned "anthropology of science", for example, mapped scientific activity as a system of beliefs, oral traditions and culturally specific practices. He highlighted social forces and the historically uneven manner in which scientific theories have been accepted. He argued the acceptance (or rejection) of scientific theories was a matter less of evidence than ideology.

Whichever way you look at it, brain diseases pose the greatest health burden of any disease group, costing the Australian government more than $400 million a year in pharmaceutical benefits, and about $2 billion in disability support pensions. That says little of the personal costs to individuals and their carers.

While neuroscientists focus their efforts on nerve cell networks (seen as ultimately determining human personality and choice), a clear message for the public is that maintaining nerve cells is crucial.

Professor Horne says neurodegenerative disorders are, basically, disorders of "cell maintenance".

Humans have about 100 billion nerve cells, or neurons, in the brain and each cell makes some 10,000 connections with other cells. The cells talk to one another via long protoplasmic fibres called axons, which carry signal pulses to parts of the brain or body, activating muscles or causing the secretion of chemicals such as hormones.

"There are two important cells in the body of which you've got your quota for life, and that's muscles and nerves," Professor Horne says. (He calls his life's work "a grand obsession", and is keen on analogies to explain the nature of brain disease.)

"If you think of cells as being factories, or houses, they have their own little economy. If you're going to be in a house for 70 years, you're going to have to be fairly meticulous in cleaning and maintaining it, otherwise it will fall into disrepair. Whereas if you've got the opportunity of changing your house every month, then you just rebuild a new one when it gets trashed — which is what we do with blood cells, gut cells and liver cells.

"But neurons, we've got them for life. So maintenance matters."

Florey scientists suspect that neurodegenerative diseases result from a problem of "impaired removal of damaged proteins" from nerve cells. It's a simplistic hypothesis, Professor Horne says, because they don't know that for sure.

"What we do know is: each of them has a signature protein, and that accumulates in the brain either inside the cell or outside it."

That protein for Parkinson's, one of Professor Horne's specialties, is alpha-synuclein. It came to prominence only in 1995, and is thought to be the main protein inside the Lewy body, the clump of protein that accumulates inside cells that are damaged in Parkinson's.

The discovery kicked off its own neurobiological revolution, as scientists grappled to understand what alpha-synuclein does and how it "misbehaves".

At the Florey, scientists have been able to measure alpha-synuclein in the blood, finding that people with high levels suffer worse Parkinson's.

"And we think that the blood cells in people with Parkinson's disease have a shorter lifespan," he says. "We don't know whether that's a reflection of bad housekeeping in those cells or whether in fact as the cells become tired, they chuck the alpha-synuclein out."

Scientists hope such research will provide a model of what's going on in brain cells — yet it's just a step on the long road to understanding brain diseases.

Still, Professor Horne says brain science has come a long way in his time: about 40 years ago, as a medical intern at The Alfred hospital, he saw Melbourne get its first coronary care unit.

"We're just beginning to be in that place in brain research; we've come there in the past 10 years," he says — and that leaves a wealth of problems to solve.