Geoffrey Burnstock obituary

Neuroscientists typically go into the field because they are captivated by the mystery of how the physical matter of the brain processes all our thoughts, emotions and sensations. Geoffrey Burnstock, who has died aged 91, started with an interest in the nerves that control the guts of guinea pigs, and discovered a completely unexpected and ubiquitous signalling system that plays a role in pain, blood clotting and immunity as well as a wide range of brain functions.

A self-described “oddball”, Burnstock never ignored an unexpected result, or discounted it because it did not fit the conventional view. He made the highly controversial discovery that ATP (adenosine triphosphate), a molecule well known to biochemists for its role as a source of energy inside cells, could also transmit signals between them.

He went on to show that, contrary to the doctrine laid down by two Nobel prize winners, Sir John Eccles and Sir Henry Dale, individual nerve cells could release more than one neurotransmitter. His revelations of unexpected diversity in the way cells communicate launched a flourishing area of research into many conditions including cancer, Parkinson’s disease, Alzheimer’s disease, visceral pain and incontinence, and to new approaches to treatment.

Burnstock conducted a critical experiment while working as a senior lecturer in zoology at the University of Melbourne in Australia in the late 1960s. As a young researcher he had developed an interest in smooth muscle, the tissue that makes up the walls of the gut, bladder and uterus. Its contractions are controlled by the largely unconscious action of the autonomic nervous system. Burnstock’s lab had developed a method of observing and recording activity in isolated strips of guinea pig gut with their associated nerves, testing a range of chemical and electrical stimuli.

To his surprise, he found that the muscle still relaxed even after he had blocked the only known transmitter molecules that operated in the autonomic nervous system.

After a lengthy process of elimination, he came to the conclusion that the transmitter in this case was ATP. As ATP is a purine nucleotide, in 1972 he coined the term “purinergic” transmission for this new phenomenon.

The world of neuropharmacology struggled to digest this heretical discovery. ATP is widespread in living tissue: how could it possibly act as a messenger? One scientist even threatened to devote his life to disproving the purinergic theory. Undeterred, Burnstock went further and showed that cells in other parts of the autonomic nervous system released both the classical neurotransmitter noradrenaline and ATP, in breach of Eccles’s and Dale’s dictum. Not until the early 1990s did evidence emerge that finally convinced the doubters. New techniques in molecular biology made it possible to isolate and identify a family of receptors on cell surfaces for ATP and its breakdown product adenosine; and Burnstock’s team threw themselves into discovering what happened when they activated or blocked these receptors.

Purinergic receptors have since turned up in a wide range of tissues, including brain, kidney, bones, lungs and many more: coffee, for example, exerts its stimulating effect because caffeine blocks purinergic receptors in the brain. Burnstock collaborated widely with pharmaceutical companies, testing their compounds in his laboratory, and also with surgeons wanting to learn more about the role of purinergic receptors in disease. One of the most successful drugs to emerge from these efforts is the blood thinner clopidogrel, prescribed to heart attack and stroke patients.

Burnstock was born into a working-class Jewish family in west London, one of two children of James Burnstock, who had been seriously injured at the Battle of the Somme, and Nancy Green. He grew up in Ealing, and during the second world war attended Greenford county grammar school, where he introduced a school-wide craze for table tennis. He took further science courses at Kingston College of Technology after his national service, but was unable to get into medical school as he had wished. Instead he won a place at King’s College London to read theology (he was an atheist), and later switched to zoology. His father having died, he spent his weekends working in a graveyard to support his mother.

With little guidance, he began a PhD at King’s on the nervous control of gut motility in fish, fascinated by the observation that goldfish eat all the time, while pike eat only once every two months. He successfully completed his thesis after asking the eminent neurophysiologist JZ Young at University College London to take over as his supervisor in his final year. At UCL he met Nomi Hirschfeld, a PhD student in cell biology from New Zealand, and they married in 1957.

On Young’s advice, Burnstock spent time in the lab of Wilhelm Feldberg at the National Institute for Medical Research, Mill Hill, learning how to record the electrical signals that activate muscles in the guts of mammals. While at Mill Hill, he and a Swiss scientist, Ralph Straub, adapted a method previously used in nerve fibres to study smooth muscle. He was so successful that Professor Edith Bülbring, the leading smooth-muscle researcher at Oxford University, invited him to come and work with her. Influenced by the classless congeniality of an Australian colleague he met at Oxford, he moved to the University of Melbourne as a senior lecturer in 1959, later becoming chairman of the zoology department.

In 1975 he returned to London as head of the department of anatomy and embryology (later anatomy and developmental biology) at UCL. He led a large and vibrant research group, with many overseas visitors, all fired by his passion for discovery. He was an enabler, encouraging colleagues to pursue their own ideas while he obtained the necessary funding and equipment: the department consistently achieved top rankings under his leadership. He was elected a fellow of the Royal Society in 1986 and received many other honours.

Burnstock stepped down as head of department in 1997, and UCL moved his research group to the Royal Free hospital. He ran the Autonomic Neuroscience Institute there until 2004, thereafter serving as its president and continuing his research collaborations, lecturing and writing. Science was both his passion and his pleasure, and he never stopped thinking of new research ideas. In 2009 he speculated that pain relief through acupuncture might depend on purinergic transmission: researchers in China and elsewhere have now amassed evidence in support of this hypothesis.

For relaxation, Burnstock carved figures in wood, often representing mothers and daughters. In 2017 he and Nomi moved back to Melbourne, where he was an honorary professor at Melbourne University. In 2018 he was made a Companion of the Order of Australia.

He is survived by Nomi, his daughters, Aviva, Tammy and Dina, and seven grandchildren.