Centurion of the cerebrum

May 22, 1998

Worldly wise: 5

Japan's Brain Science Institute is working on preventing Alzheimer's, Parkinson's and schizophrenia. If it succeeds, it will rewrite our knowledge of the brain. Martin Ince meets the man at the forefront of the research, Masao Ito.

If anyone doubts Masao Ito's status in the Japanese elite, the evidence is in London next week for all to see. He is one of the select entourage accompanying Emperor Akihito on his visit to the UK. During the visit Ito, a foreign member of the Royal Society, will be present as the emperor becomes the first recipient of the society's Charles II medal, designed for visiting heads of state who have made significant contributions to science.

But in Japan, Ito's role is far from ceremonial. Now 69, and tipped as a Nobel prize contender, he retired nine years ago from Tokyo University to become one of the horde of Japanese academics to build interesting careers after the mandatory retirement age imposed by Japan's national universities, with their civil service terms and conditions.

Ito's base is now at Riken, the Japanese government's physics and chemistry laboratory in Saitama, west of Tokyo. Riken was opened 80 years ago but its brain science institute, which started last year, could, Ito says, soon outgrow the rest of the organisation. "The Brain Science Institute started with 30 people. Now it has 150 people in 22 laboratories and we plan to have 50 laboratories and 500 people." Most are biologists, typically biochemists, molecular biologists or pharmacologists, and there are also medical scientists and a growing number of computer scientists.

In part, the fast growth of the institute (Ito is its director) has to do with new research priorities decided on by the Japanese government. Its work is organised into four main areas: understanding the brain, protecting the brain, creating brains, and a group to cope with the fast-changing science of brain technology. The last of these, Ito stresses, is far from being just a technical support unit. "New methods such as magnetic resonance imaging allow us to observe the brain without touching it. New methods are emerging all the time, including ways to observe molecules in the brain that produce fluorescence when a specific cell is activated."

The highest political expectations have been placed on the brain protection programme, under which work will be carried out to prevent fast-growing diseases such as Alzheimer's, Parkinson's, schizophrenia and depression. But all these diseases are to do with the presence or absence of specific genes in people's make-up, which means that solving them demands basic research. Ito says: "Schizophrenia may involve about 10 genes, which means that it is hard to develop a therapy for it, but that is the objective."

The political enthusiasm for the BSI arises partly because of a Japanese government panic about the ageing population, which, in Japan, as in other countries, means rising healthcare bills. Ito says that the institute has ambitions to produce drugs and treatments that can be used by doctors, although the road to such results is a long one. "Several of our groups are doing work that could lead to treatments, and there are pharmaceutical firms interested in collaborating with us," he says, citing a group working on genetic disorders, a developmental group using zebra fish and transgenic mice, and groups working on ageing and on brain recovery as being the most likely producers of new drugs and treatments. But he adds that developing such treatments could be a 20-year task. Nor are the Japanese and other denizens of the developed world going to be the only winners. The institute's work on developmental brain disorders, many of which are associated with childhood malnutrition, is more likely to be applied in the developing world.

Ito is encouraged that the Japanese government sees the 21st century as one for biological sciences, and brain science in particular. He says that politicians sometimes ask him half-jokingly why Japan needs a complete century for the brain when Europe is getting by with a decade of the brain. (It coincides with the 1990s.) For this is long-term research.

Much of what the BSI is doing will take perhaps 30 years before benefits are available to the public. Ito says that he started out by insisting to government that a 30-year commitment to the institute was essential, but discovered that 20 years was as far as even Japan's famously long-term government thinking would stretch. He says: "There is to be a detailed scientific review every five years and we think that there will be some nice outcomes to show at each of these points. When it came to getting long-term funding the government was happy but the scientists were harder to convince. They are honest and do not want to cheat society if no good results are appearing."

If it succeeds, the Brain Science Institute will rewrite our knowledge of the brain and how to care for it. Despite his tight grasp on managerial and administrative concerns, Ito is at his most enthusiastic when discussing the brain itself, especially the 10 per cent of it that comprises the cerebellum, the foundation of his own research career. As he says: "The other parts of the brain, especially the cerebral cortex, are complex and difficult, but the cerebellum is smaller, very strategic to the brain as a whole, and structurally very beautiful." In the mid-1960s, Ito discovered how the cerebellum works. It is controlled by about 30 million so-called Purkinje cells, (a small number compared with the billion neurons in the brain as a whole), which adapt their behaviour using a process called long-term depression. The result is that the cerebellum can be a memory device, altering its behaviour in response to the signals it receives.

The cerebellum of a baseball player practising strokes, for example, will gradually alter over time to replace less successful patterns of cell connection with more successful ones. In the same way, thought as well as movement can become more automatic with practice. As Ito says, when he learnt English there was a lengthy process of reconfiguring his cerebellum. By contrast Japanese, his first language, is encoded in the speech centre of his brain. In the same way, a damaged cerebellum reduces people's ability to cope with the way things relate to each other. People with such damage can function normally in many ways but fail a test in which they say what something is for. Most people can reply "sit" to the word "chair," "eat" to "apple" or "play" to "piano," but cerebellum damage limits the ability to make such connections.

Having researched the fine structure of the way the brain works, Ito is cautious about the current fashion for thinking that we can crack the big mystery of human consciousness itself. "The mind is a complex thing that psychologists divide into elements, such as perception or emotion. We can study these as functions of parts of the brain, for example by seeing where the brain activity is when people are angry. Even that is difficult, but we do not know how to study the whole of self-consciousness." He says that "awareness" as investigated by Nobel prizewinner Francis Crick can be studied, but even this is not the same thing as consciousness. "Neuroscience has not addressed this properly yet," says Ito. "Looking at 'I-ness' would involve the whole mind and brain." But he adds that there has already been significant progress in looking at the way brain mechanisms work, and says there is "no proof that it is impossible" to study consciousness as a whole.

MAKING JAPANESE SCIENCE FIT FOR THE 21st CENTURY

Japan has almost no postdoctoral students, says Masao Ito, and instead gives tenured "assistant professor" posts to new PhDs. Having got such posts, many people stick with them until retirement. Those who do not get one tend to leave the country. The BSI plans to break this pattern by introducing five-year contracts.

The BSI also aims to address the insularity of Japanese science. "Neuroscience is moving fast and we need good communications with the rest of the world to take part. We are deliberately international and aim to recruit 30 per cent of our lab heads and researchers from abroad." The virtual non-existence of technicians is another weakness. "In Japan technicians' importance has not been recognised. They have such low status that they often try to become researchers, which they tend not to be good at."

More controversial is the "lack of animal infrastructure" for science, which Ito regards as a major weakness. He points to monkeys as an example. "In the US there are ten primate centres breeding about 8,000 monkeys a year for experimental use. In Japan we have only two - one small one at Kyoto and a larger one in Tsukuba which produces a few hundred monkeys per year used mainly forvaccine production. Research groups needing monkeys depend on captured animals whichare becoming scarce."

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