`Clockwatch Orange' drug now possible

SCIENTISTS HAVE identified three brain chemicals that control aggression, raising the prospect of a Clockwork Orange-style drug treatment for violence.

Researchers at Birmingham University say the chemicals may help to determine why some mild-mannered car drivers turn into snarling maniacs when they get behind the wheel. The chemicals, called neurotransmitters, have been shown to reduce the normal aggressive response.

The work is controversial because it suggests that control over aggression can be achieved through chemical rather than social means. In the Stanley Kubrick film A Clockwork Orange, Alex, the leader of the Droogs, a violent gang, is subjected to a combination of drugs and social conditioning that breaks his spirit. The film, banned in Britain since it was made in 1971, was seen as a metaphor for the inappropriate use of mechanistic methods to deal with social problems.

Dr Thelma Lovick, who leads the research team at the department of physiology at the University of Birmingham and is supported by the Wellcome Trust, said the study of normal aggression could lead to treatments for abnormal aggression.

"Aggressive behaviour has undoubted survival value but in modern Western societies physical challenges to personal survival are uncommon. On the other hand, modern urban living presents mental challenges and conflicts over which the individual has no control. Most people have experienced intense frustration or blind fury when the impulse to violence can hardly be contained.

"My goal is to establish how the system works normally. If one knew how aggression was normally controlled, in the long term one might be able to help people in whom aggression was uncontrolled by giving them more of what they are missing."

The three brain chemicals identified by the research team are 5-hydroxytryptamine (5-HT) which has been associated with depression, anxiety and panic disorder; nitric oxide, a chemical messenger in the nervous system; and Gamma Butyric Amino Acid (GABA), which has inhibitory actions in the brain.

In a forthcoming paper in The Neuroscientist, Dr Lovick, a reader in neuroscience, describes the transmitter systems involved in panic- aggressive behaviour - the "headless chicken" syndrome. Earlier work on a strain of mice missing the gene for an enzyme that produces nitric oxide showed they were more aggressive, demonstrating the importance of nitric oxide in controlling aggression.

It has been known for 30 years that electrical stimulation of certain areas of the brain by inserting electrodes into them can produce aggressive responses. Three of these "defence" areas have been identified - the amygdala, the hypothalamus and the periacqueductal grey matter (PAG). Injection of tiny quantities of 5-HT into the PAG in the brains of mice reduced aggression. That was prolonged by the effects of nitric oxide.

Dr Lovick said: "The presence of such a control system raises many interesting questions. Could defects in the system predispose the development of aggressive behavioural traits?"

In humans, genetic factors may influence levels of aggression. A study of one family with a genetic mutation that affected monoamine metabolism (5-HT is a monoamine) showed they had a high level of impulsive aggressive behaviour. "The message is clear: we underestimate at our peril the organic causes of aggressive anti-social behaviour," Dr Lovick said.

However, critics say that giving biological accounts of social behaviour is simplistic. Simon Wessely, professor of psychiatry at King's College Hospital, London, said violence related to a psychiatric disorder could be controlled by treating the disorder. "You might be able to moderate one of the pieces of the jigsaw that leads to violence but the idea of a drug to treat violence is ludicrous. It is not a biological thing like epilepsy or cancer. It would be like a drug to treat theft. It doesn't make sense."