Leslie Iversen, a friend of friends and an inspiring light in neuropharmacology
Leslie Iversen, a giant of modern neuropharmacology, passed away peacefully on July 30, 2020, after a life of leading transformational discoveries in the biochemical pharmacology of catecholamines. He suffered from Parkinson’s disease, a condition that basically resides in a loss of dopamine in the brain centers that regulate locomotion. For a man who made transformational discoveries about catecholamines, this was an ironic turn of events.
Iversen’s major contributions to his scientific field, as well as his awards and honors, have been amply documented, their magnitude reflected in his election as a Fellow of the Royal Society and an International Fellow of the National Academy of Sciences, as well as of ‘being received the highest order of the British Empire Award: Commander of the Order of the British Empire for his services to pharmacology.
Leslie Iversen has led a scientific life with a stellar trajectory at the University of Cambridge, the Medical Research Council (MRC), Merck, the Sharp & Dohme Neuroscience Research Center and as a Visiting Professor of Pharmacology at the University of Oxford. Who was Leslie Iversen? Despite all these accolades and titles, to his friends and close colleagues he was known as “The”. Les was an extraordinarily intelligent individual with a special talent for identifying what were the most important and significant issues in neuropharmacology and neuroscience. He married an equally intelligent person, Susan Kibble (later known as Susan Iversen), whom he met during his undergraduate years at Cambridge. The Les-Sue relationship, aside from being a happy marriage, was also a mutually rewarding interaction. Sue benefited from Les’s discoveries in neuroactive molecules and her extensive repertoire of illustrious visiting scientists, while Les benefited from Sue’s in-depth knowledge of experimental psychology.
An excellent reflection of this scientific partnership has been the launch, as editors, of numerous volumes of the Manual of psychopharmacology, a series that for many years brought the latest developments linking pharmacology, neuroscience and experimental psychology. In a similar vein, Les and Sue, along with Les’s close friend Floyd Bloom, wrote the much-cited book Introduction to neuropsychopharmacology (1). Les’s deep and transformational scientific findings have recently been laudably summarized by friends and colleagues, such as Trevor Robbins (2) and Solomon Snyder, Bevyn Jarrott, Anthony Turner and Phillip Beart (3).
How did this quintessential British scientist, representing the best of Oxbridge meritocracy, come about? Behind him there were no generations of academics, nor did he come from a traditional peerage family or hereditary landowners. He came from an unpredictable corner of Exeter. Les was the son of a Danish immigrant family and his father was a branch manager of the Danish Bacon Company. He graduated from high school with high marks, which earned him a scholarship to join the exclusive Trinity College Cambridge, where he enrolled in the Natural Sciences program with botany as a subject of study. . In an interview, Les confessed that botany was his childhood passion. However, he adds: “I decided to change subjects because the teaching was very, very old-fashioned, based on a systematic classification of plants. They hadn’t even heard of biochemistry, which I found much more exciting. So I moved on to a three-year degree in biochemistry, which was, and still is, a very strong subject at Cambridge ”(4). This comment says a lot about Les’s personality. He needed constant intellectual challenges, an aspect reflected in his extraordinary list of foundational discoveries. However, Les never gave up his passion for botany, which later translated into gardening. Her beautiful garden in her home on Hills Road in Cambridge was a reflection of that lifelong passion for plants. I remember well a long walk with Les discussing science and life, on an Italian rural road with little traffic, with intermittent breaks as Les pointed out, with great enthusiasm, the presence of plants and shrubs. uncommon, identifying them by their Latin names.
Les completed a doctorate at Cambridge under the successive supervision of Gordon Whitby and Arnold Burgen and, following the path of catecholamines, with a most successful postdoctoral experience with Julius (“Julie”) Axelrod at the peak of his research, leading to his Nobel prize. Les brought new fundamental aspects related to the absorption and release of catecholamines, while establishing a long-standing friendship with Julie and Jacques Glowinski. In his second postdoctoral position at Harvard in the Kravitz lab, Les made a fundamental contribution, strengthening the inhibitory role of GABA released by neurons, then a “young” amino acid neurotransmitter.
Shortly after returning to Britain, Les published his bestseller on Absorption and storage of norepinephrine in sympathetic nerves (5), a book that I read during my first postdoctoral experience in Argentina as the “bible of catecholamines”. It was there that I knew I wanted to meet this scientist. Upon my return from Antarctica in 1968, I was invited to a meeting on Antarctic biology at the Cambridge Scott Polar Research Institute, where I visited Les in his modest laboratory at the University of Cambridge site. at Downing. Les and Cambridge produced a deep impression and my ardent desire to join his Cambridge laboratory. After completing my second postdoctoral fellowship at the University of California at San Francisco, I went to work with Les for a third postdoctoral position. When I arrived by train in Cambridge with my wife Martha and my two little daughters, on the station platform, Les and Sue greeted us with big smiles.
They then headed the new MRC Neurochemical Pharmacology Unit (NCPU). He has built a most successful interdisciplinary unit with great young scientists, visiting fellows and talented graduate students. On my first day in the lab, I told Les what I would like to work on. He said “good … but first I want you to develop a very sensitive radioenzymatic test to measure catecholamines.” I replied, “Les, I am not a biochemist. Les said quietly, “Anyone who has shown that they measure catecholamines with fluorescence tests is a biochemist to me.” The proposed technique involved isolating the enzyme catecholamine methyl transferase (COMT) and in my last resistance gesture, I said, “I may be a biochemist, but I have never worked with enzymes. Les’s last verbal punch was, “I’ll tell you what Julie [Axelrod] said. With enzymes, the only thing you have to do is keep them cold. Thus was born the first highly sensitive radioenzymatic assay of catecholamines and applied by many until the HPLC era. This exchange also reflected his quiet but firm determination to break down new barriers and extract the maximum potential from interns and collaborators, often far beyond our personal expectations.
After Cambridge, I returned to Argentina to find a country plagued by extreme political violence. My life was in danger and we decided to emigrate. Among the offers from the US and UK came an elegantly handwritten letter from Les inviting me to join the NCPU as a member of the MRC science staff, a letter that changed my life and that of my family. Les headed the NCPU from 1971 to 1982. The unit first functioned within the Department of Pharmacology, later becoming its Neurobiology Division upon Les’s departure when he took over as Head of the Research Center. in Neuroscience Merck, Sharp & Dohme.
For many of us “the children of Iversen”, the years spent at NCPU represented the best scientific output of his career, with many firsts on the biochemical pharmacology of catecholamines, absorption and release of neurotransmitters at. from a tiny central nervous system, dissected and identified under a microscope. domains, discovery of “dendritic” dopamine release, identification of new peptides in the spinal cord and brain, their stimulus-dependent release, evidence that enkephalins blocked the release of substance P from the terminals sensory nociceptives; and fundamental aspects of GABA pharmacology, including its occurrence in neurons and glia. This extensive menu of biochemical pharmacology also included some of the earliest translations of these findings in the healthy human brain and under neurodegenerative conditions, work that established fundamental contributions to “Brain Chemistry,” as Les titled his article by 1979 in American scientist (6), a perspective of brain chemistry that arises from his research experience and his discussions of the limits of neuropharmacology and neuroscience with many, including Floyd Bloom, Solomon Snyder and Masanori Otsuka, as well as with the great list of NCPU trainees (the children of Iversen).
There was no barrier at NCPU between Les, staff, visiting scientists, and graduate students. The T-shirt lab logo was a portrait of Winnie the Pooh holding a brain with the words “A brain with a little bear”. Often times, the research projects were discussed sitting on the lawn outside the NCPU, at parties at Les and Sue’s, or over a common beer ending the research week on a Friday afternoon.
The last time I met Les was on March 29, 2018, at the idyllic Corbett’s Cottage in Wiltshire, UK, which Les and Sue shared with their daughter Amy and their family. We had a long conversation, exchanging the latest information on all of the main characters in the old NCPU. He asked me what I was doing. I told her that I had just given a keynote speech in memory of Rita Levi Montalcini at an Alzheimer’s meeting in Turin and mentioned that I had shown a video of the metabolic pathway of NGF, a metabolic pathway that he had previously defined as “a nice detective story.” He asked me to show him the video. I brought my laptop and at the end of the presentation, Les asked: “Claudio, can I get a copy?” It was a much appreciated compliment and our farewell meeting.