Hans Thoenen: A modest man whose discoveries had a lasting impact on modern neuroscience

Hans Thoenen (1928–2012) was born in a beautiful alpine village in the Berner Oberland in Switzerland and retained the strong feelings for freedom and independence characteristic of Alpine dwellers. In his younger days he was a passionate mountain climber, both in the Swiss Alps and further afield, and he retained this fearless approach in his research, willing to take on new ideas and methodologies and to develop them.

Hans Thoenen.

After medical training in Berne, Thoenen joined the research laboratories of the Swiss company Hoffmann La-Roche, where he undertook basic research under the guidance of Willy Haefely. Thoenen worked on the idea that by offering novel substrates for biosynthesis it was possible to generate “false transmitters” in sympathetic nerves. He applied this theory to α-methylDOPA and other substrates including 5-hydroxyDOPA to generate 5-hydroxydopamine. However, the closely related 6-hydroxydopamine proved unexpectedly toxic and caused the selective degeneration of sympathetic nerve endings (1). Thoenen used 6-hydroxydopamine as a tool to cause “chemical sympathectomy” and explored its molecular mechanism of action. It was subsequently shown that the intracerebral injection of 6-hydroxydopamine could be used to cause selective lesions to dopaminergic pathways in brain, and this has become a standard means of generating an animal model of Parkinson disease.

Thoenen then spent an influential year in Julie Axelrod’s laboratory at the National Institutes of Health. As many of us had found previously, Julie proved a creative stimulus to Thoenen’s research. Together with Axelrod he made the unexpected discovery that chronic stimulation of the adrenal medulla led to increased levels of the monoamine synthetic enzyme tyrosine hydroxylase (2, 3). This finding was the first example of a change in gene expression triggered transsynaptically by presynaptic nerve activity. Thoenen and others went on to explore this finding in detail and to show that it was a general phenomenon.

After his stay in the Axelrod laboratory, Thoenen returned to the newly formed Biocenter of the University Basle, where his research switched to NGF and other neurotrophic factors. It is this body of work for which Thoenen is best known. A key early finding was that NGF was selectively taken up into sympathetic nerve endings and then retrogradely transported along their axons to the cell bodies, where NGF could influence gene expression. Ian Hendry, an Australian student in my Cambridge laboratory went to Thoenen’s group in 1974 and joined in this discovery (4). The selective retrograde axonal transport of trophins and other large molecules was shown to be common and helped to explain in part how the trophins acted in the nervous system. Thoenen and colleagues subsequently identified other trophins, notably brain-derived neurotrophic factor and the cloning of this and ciliary neurotrophic factor (5, 6). The neurotrophin family eventually grew to half dozen or more (7). Almost all of Thoenen’s work in Basle and subsequently as first director of the Max Plank Institute of Neurobiology in Munich focused on understanding the role of these various modulatory proteins, and the factors that influenced their expression and release, including presynaptically released neurotransmitters, other trophins, stress, and glucocorticosteroids (8). Strains of mice lacking expression of a particular neurotrophin were used to study their roles. For example, mice lacking expression of brain-derived neurotrophic factor had impaired hippocampal long-term potentiation, thought to be a model of neuronal plasticity and memory (9).

Those of us lucky enough to have interacted with Hans Thoenen, and to have enjoyed the rigor of his scientific arguments and the generous hospitality that he and his wife Sonja offered to visitors, will miss him greatly.

A recent autobiography is available in The History of Neuroscience Vol 6 (10). For a warm tribute from a close colleague, see Yves-Alain Barde’s recent obituary of Hans Thoenen in Neuron (11).