Afflictions of the mind and brain, from stroke to schizophrenia, remain among the most challenging to treat, even after more than half a century of discoveries about the brain’s biochemistry and how it responds to drugs. The neuropharmacologist Leslie Iversen, who has died aged 82, devoted his career to making sense of the interplay of signalling molecules in the nervous system that might provide sites where drugs could act.
After directing laboratories in both the public sector and the pharmaceutical industry, in his later years Iversen chaired the government’s Advisory Council on the Misuse of Drugs (ACMD). He favoured a harm-reduction approach to substance use, supporting both the decriminalisation of the recreational use of cannabis and research into its possible medicinal benefits.
Iversen pioneered research into how neurons and other cells in the brain recover excess chemical neurotransmitter, and explored these mechanisms as targets for psychoactive drugs. Signalling in the brain is a precisely calibrated process, as active neurons release tiny amounts of transmitter across junctions between cells. For the responses to be properly modulated, any unused neurotransmitter needs to be quickly cleared away. Iversen helped to reveal how neurons recover this unspent material through specific transporter molecules in their cell membranes, like archers retrieving arrows that have missed their target so that they can be used again.
Early in his career, while working with the future Nobel prize-winning biochemist Julius Axelrod at the National Institutes of Health (NIH) in Bethesda, Maryland, he was one of the first to pick up on the finding that the tricyclic antidepressants, then widely prescribed, worked by blocking the reuptake of the transmitter noradrenaline. Some of today’s most widely used antidepressants, such as Prozac, work by selectively blocking reuptake of neurotransmitters, principally serotonin but also noradrenaline, and Iversen’s work on the detail of such mechanisms greatly increased understanding of how such drugs exert their effects.
In 1970 he was granted the accolade of his own Medical Research Council research unit, the Neurochemical Pharmacology Unit (NCPU) in Cambridge, UK. A relatively small unit with around 30 researchers, “Nick-Pooh” tested theories about the role of the neurotransmitters dopamine in schizophrenia and acetylcholine in Alzheimer’s disease. The unit established one of the first brain banks to collect postmortem tissue from people who had died with neurodegenerative diseases. Iversen also took a particular interest in establishing the role of a peptide known as Substance P in the transmission of pain signals.
In his later work as director of the American pharma company Merck’s Neuroscience Research Centre at Harlow in Essex, he pursued this peptide in the hope of developing new analgesics, but instead achieved one of the centre’s few major successes in drug discovery with the launch of aprepitant (Emend) to treat nausea in patients receiving cancer chemotherapy.
Iversen was born in Exeter. His Danish father, Svend, was the manager of the Danish Bacon Company’s south-west branch; his mother, Anna Caia, also Danish, came to work for Svend as a housekeeper with five sons from a previous marriage (one of them died before Leslie was born), and Leslie was the sole child born after they married. He attended Hele’s school in Exeter, then a boys’ grammar school, and after two years’ national service in the Royal Navy went to Trinity College, Cambridge, with a scholarship to study natural sciences.
On graduating in 1961 he married Susan Kibble, a fellow student, and thereafter they pursued successful academic careers in parallel – he in neuropharmacology, she in experimental psychology, her outgoing personality complementing his reserve and dry humour. After completing PhDs in Cambridge, they spent two years in the US pursuing postdoctoral research, the first year at NIH, and the second at Harvard University in Cambridge, Massachusetts.
The NCPU attracted dynamic young scientists from across the world, many of whom testified to Iversen’s sympathetic mentoring. His subsequent foray into drug development with Merck (1982-95) led to programmes focused on Alzheimer’s disease, stroke, epilepsy and pain. With a dedicated team of 300, the research output of the centre was formidable, and some of its discoveries became valuable research tools.
Ultimately, however, even this powerhouse was unable to launch more than a couple of candidates into the market in the face of the complexity of the brain, the long-term nature of neuroscience research, the rigour of clinical trials and the company’s need for profitable products.
Leaving Merck in 1995, after Susan had been appointed head of the department of experimental psychology at Oxford University, Iversen took on a number of advisory roles. He was co-opted as scientific adviser to a House of Lords science and technology select committee inquiry into cannabis, whose 1998 report, in his words, “deflated some of the more aggressive claims about the harmfulness of the drug”.
From 1999 until 2004 he was professor of pharmacology and director of the Wolfson Centre for Age-Related Diseases at King’s College London. He went on to write a popular book on cannabis, The Science of Marijuana (2000), as well as Drugs: A Very Short Introduction (2001) and Speed, Ecstasy, Ritalin: The Science of Amphetamines (2007).
Not long after joining the ACMD, he took over as interim chairman in 2010, then chairman of the council, after the home secretary, Alan Johnson, sacked his outspoken predecessor, David Nutt. He also chaired the board of Acadia, a small pharmaceutical company in California, which has successfully launched a treatment for hallucinations and delusions in people with advanced Parkinson’s disease. Iversen himself received a diagnosis of this disease and gave up his many activities only when forced to by ill health.
Up to that point his main outside interest was gardening – he was a serious plantsman with a particular fondness for unusual dahlias and hellebores – and he was an eclectic reader “who knew something about everything”, according to his daughter.
He was appointed a fellow of the Royal Society in 1980, and in 2013 made a CBE.
Iversen is survived by Susan and their children, Benjamin and Amy, and seven grandchildren. Another daughter, Emily, died in infancy.
• Leslie Lars Iversen, neuropharmacologist, born 31 October 1937; died 30 July 2020