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A fascinating scientist, Ulf Svante von Euler-Chelpin, was born in 1905 in Stockholm. Before highlighting the biography of this unique person, we announce the von Euler Award for Neurohumoral Control!

This award will be granted to the authors of a seminal study published in Acta Physiologica. The focus of the manuscript will be in the broader field of neurohumoral control, including areas such as cardiovascular, gastrointestinal, metabolism, temperature control and renal physiology.

von Euler's background is highly academic and cosmopolitan: his mother, Astrid Cleve, is said to have been the first woman in Sweden to receive a doctoral degree. That was in 1898. Later, she became a professor of botany and geology. Cleve's father, Per Teodor, was a professor of chemistry and discovered the elements erbium, holmium and thulium.

The other family branch excels as well. von Euler's father, Hans von Euler-Chelpin, became a Nobel Laureate in Chemistry in 1929. Hans was of German origin and distantly related to the famous Swiss mathematician Leonhard von Euler, active in Petersburg during the eighteenth century. Taken together, it is no wonder that Ulf von Euler was to become a scientist.

von Euler stood out early. At the age of 17, von Euler published his first scientific paper, as a co-author of his father. An important inspiration in his scientific development was probably the Twelfth International Physiological Congress in Stockholm (1926) where he had the opportunity to meet all the great physiologists of the time (I. Pavlov, E.H. Starling, J. Barcroft, Otto Loewi and many others).

von Euler's early training took place in the laboratory of Göran Liljestrand, Professor and Chairman of the Department of Pharmacology at Karolinska Institutet. There is no question that Liljestrand had a great influence on his scientific career. von Euler comments that ‘it is hard to imagine a more helpful and stimulating teacher and co-worker’. Liljestrand was intrigued by Heyman's discoveries around 1930 of the roles of chemoreceptors in the control of respiration and (to some extent) the systemic circulation. Together, von Euler and Liljestrand addressed the ‘old question’ of regulation of the pulmonary circulation, which had been ongoing ever since 1894, when JR Bradford and HP Dean had reported that asphyxia causes a rise in pulmonary arterial pressure. In a joint study in 1945–1946, Liljestrand and von Euler showed conclusively that oxygen lack as well as excess carbon raises the pulmonary arterial blood pressure in the spontaneously breathing cat. They concluded that this direct vasoconstrictor effect constitutes a chemical mechanism for diverting the pulmonary blood stream towards better ventilated parts of the lung (von Euler & Liljestrand 1946). This clinically important discovery, a mechanism assisting ventilation–perfusion matching in the lung, is currently referred to as the ‘von Euler and Liljestrand vasoconstrictive reflex’ and was published in our journal.

In 1930, von Euler defended his thesis and then went to London, supported by a Rockefeller Foundation Fellowship, to work in the laboratory of Henry Dale, the leading expert on the chemical basis for autonomic neurotransmission (and later, recipient of the Nobel Prize for Physiology or Medicine, in 1936). After returning to Karolinska Institutet, von Euler was appointed Assistant Professor in pharmacology, and in 1939, Professor and Chairman of the Department of Physiology, a position he held until his retirement in 1971.

From 1957 to the end of his life in 1983, he was chief editor of our journal, a position in which he succeeded Göran Liljestrand.

Ulf von Euler's scientific productivity is amazing; altogether, he published 465 papers over a period of six decades. His ‘Leifmotif’ was clear: to find the chemical signals that mediate control of physiological events. Three of his discoveries that have turned out to be of the most fundamental biological importance are following:

In 1930, he made his first major discovery while he worked in Dale's laboratory. In collaboration with a senior colleague, J.H. Gaddum, he noted that extracts of brain and intestine behaved in part similarly, in part differently from the reference Substance, acetylcholine. Both contracted the gut in an organ bath, and both lowered the blood pressure of the anesthetized rabbit, but while the effects of acetylcholine were abolished by atropine, those of the extracts were not. Preparations of the unknown Substance were labelled ‘P’. And thus, essentially by accident, the active ‘principle’ became known as ‘Substance P’. Driven by intuitive appreciation of its potential biological importance, von Euler patiently followed up his discovery by describing the polypeptide nature of Substance P, methods of its purification and assay, its general distribution in the body and the biological effects of the, still relatively crude, preparations available at the time. The breakthrough came much later, when the chemical nature of Substance P became fully elucidated by Chang and Leeman, some forty years after von Euler's original discovery, and pure Substance P became available. This enabled Tomas Hökfelt to show by immunohistochemistry that Substance P occurs selectively within some neurons. Various functions of Substance P remain to be fully unravelled. Today, it is known to act as a neurotransmitter and/or modulator, notably in transmission of signals from primary afferent pain fibres, but also to the myogenic tone in the gut (Baylie & Brayden 2011). The Substance P discovered by von Euler has thus turned out to be the first member of an intriguing, now rapidly expanding class of ‘neuropeptide transmitters’.

Ulf von Euler's second major discovery was made in 1934, after he had returned to Karolinska Institutet. In extracts of seminal fluid or prostate or vesicular glands, he found an unknown ‘principle’ which, similar to Substance P, mimicked the effects of acetylcholine on test preparations, but whose effects were atropine-resistant. Somewhat unfortunately, because it was first found in extracts of the prostate, he named it ‘prostaglandin’. During the next few years, he was able to define prostaglandin as an unsaturated, lipid-soluble, nitrogen-free organic acid. He subsequently described tissue sources, methods of extraction and purification, and basic pharmacological properties of the available, still crude, preparations. The breakthrough came when the biochemist Sune Bergström proceeded further with the chemical analysis. Using a newly developed technology, Bergström succeeded in the late 1950s in the first purification of a prostaglandin. von Euler wrote in the journal Progress in Lipid Research that ‘a discovery is in principle like an invention, or even a piece of art…. It is sometimes said that the prostaglandins lay dormant for some 20 years after their discovery. This is not exactly true, since Sune Bergström took over in 1945 where I left it, and with consummate skill and perseverance conducted the chemical work to isolation and identification, thus starting the second stage of prostaglandin history’. Bergström showed that ‘prostaglandin’ is not a single Substance, but a family of biologically active compounds of the highest importance for many physiological functions, for example in the reproductive and circulatory systems, and also plays key roles under pathophysiological conditions (Gaetano et al. 2010, Schulzke et al. 2010, Tusgaard et al. 2011). For his discoveries in this field, Bergström shared the Nobel Prize in Physiology or Medicine 1982.

von Euler's third major discovery concerned the identity and mode of intraneuronal storage of the sympathetic catecholamine transmitter. In 1946, he settled a 40-year-old controversy concerning its identity, by showing that it is not adrenaline, as earlier assumed, but its nonmethylated homologue, N-Ohne-Radikal-adrenaline (noradrenaline). The surprise was not that noradrenaline was more closely ‘sympathomimetic’ than adrenaline; that had been shown already in 1910 using synthetic noradrenaline. But there was no evidence at that time that noradrenaline occurs naturally in the body; it was dismissed as a mere ‘synthetic curiosity’. von Euler tackled the problem by using classical pharmacological differential bioassay to determine the adrenaline and noradrenaline content of extracts of sympathetic nerve trunks or their target tissues. It became soon clear to him that the ‘sympathomimetic’ principle in the extracts was not adrenaline; ‘after many trials, doubts and guesses, it became plausible that it was noradrenaline’. This conclusion was confirmed by colorimetric and fluorimetric methods, after separation of the compounds by paper or ion exchange chromatography. Noradrenaline did not occur in the nerve-free placenta, but was present in sympathetic nerve trunks and all sympathetically innervated target tissues, in proportion to their nerve terminal density, and largely disappeared following denervation. It was, thus, clearly located strictly within sympathetic nerves, probably mainly in the terminals. Interestingly, the first original full report of this seemingly simple, but truly important discovery, the first conclusive proof that the sympathetic catecholamine transmitter is noradrenaline, was first published in our journal (von Euler 1946).

One observation that particularly intrigued von Euler was that sympathetic nerves could contain noradrenaline at such extremely high (up to 30 mm) concentrations, levels characteristic of catecholamines in chromaffin cells. How could sympathetic nerves store this extremely powerful (potentially ‘dangerous’) biological agent at such high concentrations safely, yet be ready to release it from the store in small fractions, on demand? This led him to consider the possibility that sympathetic nerves might store its catecholamines in vesicles, as chromaffin cells had been shown to do, by Nils-Åke Hillarp's group. Together with Hillarp, von Euler solved this issue directly, showing by centrifugation of homogenates of sympathetic nerves that a large part of the noradrenaline was sedimentable, that is, occurs in particulate form. By electron microscopy of the sediment, he examined the morphology of the subcellular noradrenaline-storing organelles, which he termed ‘nerve granules’. By studies of properties of successively improved preparations of his ‘nerve granules’, von Euler made pioneering contributions to a new field, the cell and molecular biology and pharmacology of the biosynthesis, uptake, storage and release of noradrenaline as sympathetic transmitter. These studies have turned out to have wider implications, because they were the first to address several of what we now know are universal mechanisms for intraneuronal storage of (almost) all neurotransmitters. To the very end, even after his retirement as chairman of the Department of Physiology in 1971, von Euler continued to play a leading role in the development of the explosively growing catecholamine field.

As recognition of his discoveries in this area and of their impact on the development of other fields, such as brain function in health and disease, and clinical hypertension, von Euler shared the Nobel Prize in Physiology or Medicine 1970 (Raju 1999, Langmoen & Apuzzo 2007).

Towards the end of his life, von Euler could look back on a uniquely successful research career. Already as a young scientist, he had had the genius – and the good fortune – to make three major discoveries. Each had grown, over time, to become one of the ‘hottest’ fields of the life sciences. How he experienced this he has commented on in a witty and instructive editorial in Circulation (von Euler 1962) that reveals some aspects of his philosophical outlook on science, such as on the art of recognizing a ‘discovery’ from an ‘observation’, concluding ‘We must always guard the liberties of the mind and remember that some degree of heresy is often a sign of health in spiritual life’. And doesn't this sound familiar? ‘There is a certain tendency in our time toward collection of data, especially with the aid of new and ingenious machines with a large output capacity. Some of these machines can easily produce miles of records. They are also expensive and the press photographers have a definite liking for them. In order to pay off the large grants received for the purchase of such machines the poor scientist has to produce a number of papers which will make it seem worth while for the granting body to have allowed such a large sum’.

To those who have had the privilege of receiving their scientific training by Ulf von Euler, there can be no doubt about his greatness as scientist and teacher. He was not an empire builder or a founder of schools for dogmatic adherents to his own views, but a believer in freedom in research. ‘Always keep an open mind – but, equally, always believe in the least sensational explanation’. New ideas in young colleagues were encouraged with a degree of enthusiasm adapted to his intuitive faith in their soundness. Whenever disbelieving, his comment might be ‘It would be most interesting if you turn out to be right…’. His openness of mind and genuine scientific curiosity, and his knack for finding the right experimental approach to test the validity of a new hypothesis made it a very educating experience to work close to him.

von Euler looked back in an eloquent, witty and instructive article: ‘Pieces in the Puzzle’ (von Euler 1971). This is highly recommended reading, especially for young (and hungry!) scientists. It describes first, with concrete examples, the excitement of a young scientist who realizes that he is making history: ‘… almost the first turn of the spade brought up a new biologically active factor, which certainly was to a large part due to luck…’. The second section of the paper gives some aspects of his philosophical outlook on science, including a discussion of what advice, if any, he would give to young scientists. This part is wise as well as witty; his sarcasms make it hilarious reading.

As a person, von Euler was aristocratic, a citizen of the world, carrying on with dignity and style the intellectual and cultural tradition that he had inherited. His dry humour and mild never destructive sarcasm made his company stimulating, sometimes even delightful. He had the great privilege to keep his full creative potential to the very end, living to see his scientific offspring mature, and rightly enjoying international recognition as a Grand Old Man of chemical information transfer.

Taken together, there can be no worthier patron for an award for neurohumoral control. It is a privilege to our journal to have had such an editor and author!

Conflict of interest

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There is no conflict of interest to declare.

References

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