Lewis Wolpert: The Sceptical Inquirer

The fishy origins of life-changing research
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The Independent Online

For all his brilliance, Burnstock was an unlikely scientist - although he remembers his first interest in science at the age of six when, with his eyes half-closed, he thought he could see oxygen particles in the air. At school he was not particularly successful and was something of a rebel.

He wanted to study medicine, and applied again and again to university, but was always turned down. So he took an alternative path by studying biology at King's College in London. He followed this with a doctorate in gut physiology, with the brown trout as his model.

He wanted to know how nerves activated contraction in the involuntary smooth muscle that controls the movement of the gut. It was known that an electrical impulse went down the nerve and then released a single substance, a neurotransmitter, which bound to the muscle membrane, and activated it. So he went to the National Institute for Medical Research at Mill Hill and there developed a method for recording the electrical activity of smooth muscle, a method still widely used.

After fellowship to the United States, and marriage, he moved to Melbourne where, with his new research group, he found that blocking all the known neurotransmitters did not stop the nerve activating the muscle. Some unknown transmitter had to be involved. In order to identify the neurotransmitter they tried many different substances and, in 1970, made the fundamental discovery that a substance called adenosine triphosphate or ATP, a universal molecule used by cells for energy, was the mysterious transmitter. He coined the term "purinergic signalling" in 1972 in a key paper that has since been cited more than 2,000 times by other key scientists. But few believed him at the time and he was ridiculed.

And then came another discovery in 1976, when he was at University College London. Contrary to universal belief, he showed that single nerves release more than just one transmitter, and that ATP was a co-transmitter in almost all nerves, including signalling between nerves in the brain. This was revolutionary. There was again fury at this claim but he was eventually proved right. The turning point came in the early 1990s when the receptors for ATP on muscle and nerves were identified.

Praise is now universal. Burnstock has written more than 1,000 papers and is the most quoted pharmacologist in the world over the past 10 years. Awards have been numerous.

These discoveries have important implications for treating conditions including pain, cystic fibrosis and cancer. All coming from the gut of the brown trout, and, as one Nobel Prize winner once wrote, Geoff Burnstock's effervescence.

Lewis Wolpert is emeritus professor of biology as applied to medicine at University College London

l.wolpert@independent.co.uk

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