| Administrative History | After passing his clinical exam, Kosterlitz was required to undertake a compulsory one-year practical session of surgery. Following this, from c 1925 - 1933, he worked as an Assistant in the First Medical Department in the University of Berlin (The Charite) where he gained further clinical experience and was able to develop his early research interest in biochemistry. For the first three years he held a voluntary position in the X-ray Department where he rose to to head of diagnostic outpatients, and from 1928 - 1933 held a salaried position in the Clinical Department. His research during this period was undertaken mostly during the evenings and focussed upon study of the altered sugar metabolism in diabetic patients.
By 1933, he was, like many of his contemporaries, keen to leave Germany and approached John James Rickard Macleod with an interest in joining his department in Aberdeen. Macleod, one of the co-discoverers (with Frederick Grant Banting and Charles Herbert Best) of insulin, had recently returned from Toronto to Aberdeen to take up the post of Regius Professor of Physiology. His continuing research in this area thus tied in closely with Kosterlitz's own interests and when Kosterlitz joined the Department of Physiology in 1934 the two men worked closely together. Following Macleod's death a year later, Kosterlitz continued his research into carbohydrate metabolism for a further fifteen years. His principal discovery during these early Aberdeen years was that galactose-1-phosphate was the important intermediate in the metabolism of galactose.
During his first nine months in Aberdeen, Kosterlitz was once more without a salary (his living expenses were met by his father). He was then recipient for a short while of an early grant from the Diabetic Association, until 1936 when he was appointed a Carnegie teaching fellow (the year in which he received his Aberdeen PhD) and in 1939, a lecturer in physiology.
Early in the Second World War Kosterlitz was briefly interned, but he soon returned to Aberdeen to contribute to the training of medical students, and to work on what he saw as a more urgent topic than diabetes, namely the effects of nutrition on liver function. He was appointed senior lecturer in 1945, and reader in physiology in 1955.
In the early 1950s he decided to change direction scientifically, and he turned his attention to the autonomic nervous system, particularly the control of peristalsis, the rhythmical propulsive action of the gastrointestinal tract. A brief period at Harvard in 1953–4, working with Otto Krayer (a distinguished expatriate German pharmacologist whom Kosterlitz had known in Berlin), kindled his interest in pharmacology, and he learned of a paper published by Paul Trendelenburg in 1917 showing that the plant alkaloid morphine powerfully inhibited peristalsis. In Aberdeen he devoted himself to studying the peristaltic reflex in isolated segments of intestine suspended in organ baths, and using this preparation to analyse the actions of morphine on the nerves involved in peristalsis. At that time several other laboratories were studying morphine's effects on the brain, and there was scepticism about the relevance of Kosterlitz's painstaking pharmacological work on the intestine. He revealed much later that he had harboured from the beginning the idea that morphine, a plant-derived substance, might be acting as a surrogate for an endogenous chemical mediator, and that his undisclosed ambition had been to discover its nature.
Kosterlitz remained a reader in physiology at Aberdeen for thirteen years until 1968 when, at the age of sixty-five, he became professor and head of the newly created department of pharmacology at Aberdeen. This finally gave him the opportunity, denied for many years, to build up and lead his own department, and he made the most of it. His group turned its attention to carrying out careful quantitative pharmacological studies of the effects of morphine-like drugs on different animal tissues. Through these studies, they showed unequivocally the existence of three types of opiate ‘receptor’ (specialized binding molecules through which drugs exert their specific physiological effects). Simultaneously, other groups in Sweden and the United States came to similar conclusions by studying the binding of opiate drugs to different tissues. The discovery of specific receptors suggested the existence of an endogenous chemical mediator which, like morphine, produces physiological effects when it becomes attached to the receptor; Kosterlitz's long cherished belief in the existence of endogenous ‘opioids’ thus gained considerable credibility.
At this critical point Kosterlitz, then seventy, had to retire from his university post, but he stayed on as director of a new, independently funded unit for research on addictive drugs, which he led for another twenty-two years. John Hughes, deputy director, played a major part in the unit's very successful research. They immediately set about identifying the mysterious endogenous substance, starting from copious extracts of pig brain, and using the pharmacological assays for morphine-like substances that they had perfected. After many set-backs, they succeeded in 1975 in isolating two novel peptides (leu- and met-enkephalin), which were the elusive endogenous opioid peptides. These short peptides, containing only five amino acids, were soon found within the sequence of much longer peptides (endorphins) produced by the pituitary gland, which also belong to the endogenous opioid family. This family of mediators, and the associated receptors, quickly became the focus of intense worldwide research activity, and proved to be involved in many brain functions, including pain perception, drug dependence, learning and memory, endocrine secretions, and much else. Kosterlitz's discovery thus represented an important scientific breakthrough, which was the basis for many subsequent advances in the pharmacology of the nervous system.
The content of the preceding paragraphs comes principally from H.P. Rang's entry for Kosterlitz in the 'Oxford Dictionary of National Biography.' |