In close collaboration with a dear colleague of his, Jean-Pierre Tranzer at Roche in Basel, they

discovered through the use of electron microscopy that this drug selectively destroys sympathetic nerve endings. They suggested that 6-hydroxydopamine is taken up by these terminals where it readily oxidizes, with its killing specificity ultimately explained by the high local concentrations created by the dopamine transporter. Hans’s desire to further explore the mechanisms of action of 6-hydroxydopamine using LY294002 mw biochemical markers led him to join the laboratory of Julius Axelrod at the NIH. While of short duration, this stay had a profound impact on Hans. First, because of the discovery of transsynaptic induction (see below) and second because of the way science was done in the Axelrod laboratory. The lack of hierarchy, the openness for unexpected discoveries

that others would perhaps ABT-888 in vitro reject as a nuisance slowing the confirmation of preconceived ideas, the unusual career path of Axelrod, including his PhD late in life, all this was interpreted by Hans as indications that, after all, there might be room in Academia not only for adventure, but also for scientists with unconventional trajectories. Long after leaving the Axelrod laboratory, Hans would often talk fondly about “Julie,” as he would invariably say. As Hans

describes in his autobiography, the discovery of transsynaptic induction was an entirely unexpected consequence of the use of 6-hydroxydopamine. Together with Axelrod and Müller, Hans showed in a series of short but remarkable publications in 1969 that increased presynaptic activity leads to elevated levels of enzyme activity, until which they illustrated with tyrosine hydroxylase. While neither antibodies nor RNA probes were available at the time to directly quantify the levels of tyrosine hydroxylase, this work showed that increased enzyme activity necessitates ongoing transcription and translation, a conclusion that was at the time quite innovative with respect to how electric signals impact gene expression. Upon his return to Europe, Hans found it initially more difficult to publish in highly regarded journals and for years, when he would run out of patience with journal editors—and this would typically happen quite rapidly—he would often use the argument that, after all, he was just a boy from the Swiss Alps, unfamiliar with the sophisticated formulations that people learn by default (he thought) when brought up in large U.S. cities. Upon his return from the NIH, Hans spent a few years again in Basel, where he was appointed University Professor.