Professor Geoffrey Burnstock
Neuroscientist who overcame establishment hostility to prove his theory of how nerve cells behave
PROFESSOR GEOFFREY BURNSTOCK, who has died aged 91, was one of the most highly regarded neuroscientists of his generation; in the 1960s and 1970s he developed a radical new theory, “purinergic signalling”, which would revolutionise understanding of how nerves communicate with structures in the body – but only after 20 years during which his theory was dismissed by many in the scientific community.
Burnstock also excelled as an academic leader over some four decades at University College London (UCL), where he was appointed head of the Department of Anatomy and Developmental Embryology (now the Department of Anatomy and Developmental Biology) in 1975, and where, from 1997, he was director and later president of the Autonomic Neuroscience Centre at the Royal Free campus.
At a time of financial constraints Burnstock turned the Anatomy department into one of the largest and most successful in the world. At its peak it had no fewer than 26 professors, including seven Fellows of the Royal Society, a sharp increase over the three professors in the department when he arrived, while regularly scoring top ratings – an achievement described by the Nobel prizewinner Sir James Black as “without parallel in UK biomedical departments” over recent years.
It was while Burnstock was working on a doctorate studying gut physiology at UCL that, using the brown trout as his model, he began to investigate how nerves activate the smooth muscle that controls the movement of the gut – part of what is known as the “autonomic” nervous system, which regulates involuntary processes such as respiration, digestion and sexual arousal.
It was known that an electrical impulse went down the nerve and then released a neurotransmitter which activated regions on the muscle membrane, called receptors. After taking his PHD he moved to the National Institute for Medical Research at Mill Hill where, with Ralph Straub, he developed a method called the sucrose gap technique for recording the electrical and mechanical activity of smooth muscle, a technique he applied at the UK’S leading smooth muscle laboratory in Oxford University’s Department of Pharmacology.
In 1959 he was appointed a lecturer at the University of Melbourne, Australia, where, experimenting on guinea pig intestines, he and two graduate students obstructed the activity of the then-known neurotransmitters, acetylcholine and noradrenaline, with chemical blocking agents.
Despite the presence of the blocking chemicals they found that the intestinal muscle still relaxed when stimulated, and concluded that another type of neurotransmitter must be present. At the time they called it the “third nervous system”.
In 1970 Burnstock discovered that a substance called adenosine triphosphate or ATP, a well-known purine nucleotide found inside every living cell in almost every living creature, was probably the mysterious transmitter, and in a key paper, published in 1972, Burnstock coined the term “purinergic” to describe the role of ATP as a neurotransmitter.
But the response to his theory was incredulity, ridicule – even anger. ATP was known to provide cells with the energy that makes life possible, but most scientists thought it implausible that it could also have a role as a neurotransmitter. As Burnstock recalled in an interview in 2008, “people used to come up, trembling, and say, ‘I’m going to devote my life to destroying the purinergic hypothesis.’ It excited a lot of negative passion.”
In 1976 Burnstock stuck his neck out even further and took a swipe at Dale’s principle, a rule accepted over decades (named after the Nobel Prize winner Sir Henry Dale) that one nerve could only release one neurotransmitter. Relying on his research and his own instincts, Burnstock deduced that nerve cells release multiple chemicals and published a paper entitled, “Do some nerve cells release more than one transmitter?”, in which he suggested that ATP was a co-transmitter.
It was later realised it was a cotransmitter in almost all nerves in the body, including signalling between nerves in the brain.
It took many more years for purinergic signalling to be taken seriously by the scientific community, mainly due to the fact that ATP was difficult to deal with in the laboratory, as effective agents for blocking it and thus for studying its activities were lacking.
The turning point came in the early 1990s when Burnstock, working with Eric Barnard, and other scientific teams in parallel, cloned, identified and characterised sub groups of receptors for ATP. Later these receptors were identified on virtually every cell type in the human body, including those activated by nerves. This proved Burnstock’s theory to be correct and raised the possibility that his discoveries could be used therapeutically.
Many others would have given up the struggle, but as Burnstock observed, his whole scientific career had been “a fight against the odds”.
One of two children of James Burnstock and Nancy, née Green, he was born on May 10 1929 in London into a Jewish working-class family and grew up in the then poor Portobello Road area, and in Ealing. His father had been badly wounded at the battle of the Somme. “We had a happy life, but a very frugal one,” he recalled.
“We only had chicken once a year at Christmas time, that sort of thing.” Geoff, as he was known, was educated at Greenford County Grammar School, but was not particularly successful there and seems to have been considered something of a rebel.
He wanted to study Medicine, and applied to several universities – only to be turned down. After National Service and a spell at Kingston Technical College, he secured a place at King’s College, London, to read Theology (though he was an atheist), eventually switching to Zoology.
His father having died, to support his mother Burnstock worked every weekend as a graveyard maintenance man. After graduation he did his PHD in fish gut physiology at UCL under JZ Young, whom he would later succeed as head of the Anatomy Department.
After a year’s fellowship in the US and marriage, in 1957, to Nomi Hirschfeld, in 1959 Burnstock was appointed to a Senior Lectureship at Melbourne University, becoming Professor and Chairman of Zoology in 1964. He would return to the university in 2017 as an honorary professor.
Burnstock’s success at UCL owed much to his support for talent and creativity against bureaucratic obstructionism. “In general, in England, if you want to do something new, the first response is, ‘it can’t be done. Don’t you know there’s a war on?’,” he once observed. “Whereas, in Australia, the first thing they say is, ‘give it a go, mate’.”
When an irate scientist who had been strung along by university bureaucrats began to knock down the wall in his office that they were supposed to do for him, instead of scolding him Burnstock joined in. When a highly valued member of his team moved to a different university, the man’s unconventional working hours were frowned upon and he eventually left. Subsequently Burnstock was talking to the head of that department who, when they happened to see a rogue black tulip in a bed of flowers, remarked that she must cut it out. That, Burnstock told her pointedly, was the one he would have done his best to keep.
Burnstock supervised more than 100 PHD students and his generosity, his refusal to take no for an answer and his passion for his subject transformed the lives of dozens of budding scientists.
His discovery of purinergic signalling has led to the development of a range of pharmaceuticals, the best known of which, clopidogrel, is widely used in the treatment of stroke and thrombosis. His discovery also has important implications for treating many conditions including pain, hypertension, osteoporosis, cystic fibrosis and cancer.
In 1986 Burnstock was elected a Fellow of the Royal Society whose Gold Medal he was awarded in 2000. He was appointed a Companion of the Order of Australia in 2018.
In his spare moments he enjoyed wood carving, jigsaw puzzles and playing tennis.
He is survived by his wife Nomi and their three daughters.