Obituary: Professor Hans Kosterlitz

Professor Hans Kosterlitz will be for ever known as the discoverer of endorphins, the body's own painkillers. This will rank as one of the major scientific discoveries of the past quarter of a century. Indeed his friends and colleagues all felt that it was worthy of the Nobel prize.

Kosterlitz was born in Berlin in 1903. When he was a medical student he undertook his studies at three different universities, Heidelberg, Freiburg and Berlin, before obtaining his MD degree from the University of Berlin in 1929. His first appointment was as an Assistant in the First Medical Department of the University of Berlin, a post which he held from 1928 to 1933.

His initial research interest was in carbohydrate metabolism and its relation to liver disease and diabetes mellitus. He was particularly interested in the clinical observation that diabetic patients have a better tolerance to fructose and sorbitol than to glucose. He confirmed the earlier work of Minkokowski that fructose could form liver glycogen in the diabetic dog in the absence of insulin, and he extended this observation to sorbitol. He also showed that diabetics utilise galactose, which is converted to glucose in the liver.

It was his interest in sugars that brought him to Aberdeen in 1934, to work with J.J.R. Macleod, who after the discovery of insulin with Banting and Best in its laboratory in Toronto in 1922 had returned to Aberdeen as Regius Professor of Physiology. Sadly Macleod died the following year; notwithstanding, Hans Kosterlitz stayed on in Aberdeen, continuing his work on galactose and the liver, and the mechanism by which galactose is converted to glucose.

Following the onset of the Second World War Kosterlitz felt that his research should be more useful and should help in the "war effort". He continued his work on the liver (some of it in collaboration with the Rowett Research Institute), by investigating how it was affected by nutrition, and in particular how the quality and quantity of protein affected its composition. This interest in nutrition continued into the 1950s.

There now becomes what looks at first sight a complete transformation in interest, to the peripheral autonomic nervous system. But was it? What stimulated his interest was a paper written by Cannon way back in 1922. Cannon reported the liberation of "sympathin" on the stimulation of the hepatic nerves, where its action on the denervated heart was greater in cats fed on milk and meat than in those which were fed mainly on carbohydrate and fat. In collaboration with Ian Innes, Kosterlitz was unable to find any differences in nor-adrenaline release depending on diet.

This interest in the autonomic nervous system eventually spread to the myenteric plexus of the gut. Still the connection with nutrition.

Reading a paper by P. Trendelenburg published in 1917, Kosterlitz learnt that morphine in very low concentrations inhibited the reflex contractions of the guinea-pig's gut. This started his interest in morphine, and his first paper on the subject was published in 1958, when, remarkably, he was 55 years old.

As the work on morphine progressed Kosterlitz began to believe that it must be an agonist (i.e. an active substance) and not an antagonist. If he were right then there must be a receptor for morphine in the body, and ipso facto there must be an endogenous ligand or naturally occurring morphine-like substance in the body which physiologically acted at this morphine receptor.

Eventually he had the opportunity to prove this theory.

Kosterlitz had remained in the Physiology Department in Aberdeen, where over the years he was an Assistant and Carnegie Teaching Fellow, Lecturer, Senior Lecturer and finally Reader. In 1968, Professor Alistair Macgregor, Regius Professor of Materia Medica, persuaded Aberdeen University to appoint him to a new Chair in Pharmacology within the Department of Materia Medica. Thus at the age of 65, Hans Kosterlitz found himself the first Professor of Pharmacology at Aberdeen University. Three years later when he was 68, Pharmacology was made a separate department with Kosterlitz as its Head.

He finally had to retire at 70, and this is when he set up the Unit for Research into Ad- dictive Drugs to look for the endogenous morphine agonist. He was successful, and in 1975 reported the discovery of the enkephalins, the greatest scientific achievement of his life and one of the great landmarks of Pharmacology.

Thus began the story of the opioid peptides, which has led us to a greater understanding of how the body deals with pain, even on understanding acu- puncture, and provides a scientific rationale for the production of new narcotic analgesics. Kosterlitz, with a whole host of collaborators, continued his research into the opioid peptides for over 15 years, publishing his final paper in 1991.

Kosterlitz met his wife Hannah in Berlin, and she came to Scotland to work in Glasgow for a while before they were married in Aberdeen. They were inseparable. Hannah was usually with him at scientific meetings and congresses, not only looking after Hans, but in particular taking under her wing the wives of younger scientists.

Hans Kosterlitz instilled great devotion in the many young workers who collaborated with him. One of the sights of the week in Aberdeen occurred every Friday afternoon when Kosterlitz and his co-workers trooped over to the Kirkgate bar from Marischal College, to discuss the week's research. His driving was also notorious - many are the times that he came into the department with a new dent in his car, complaining bitterly that some other driver had not seen him. It was only a few years ago that he finally gave up driving, when he realised that it was cheaper and more convenient for Hannah and him to take a taxi to their favourite restaurant in Cults for lunch every Saturday.

Kosterlitz was made a Fellow of the Royal Society in 1978; there cannot be many fellows elected to that august society for research carried out in the eighth decade of their life. The following year he was awarded the Society's Gold Medal. The recognition and awards he received following his discovery of the opioid peptides were legion. They included in 1976 the Schmiedeberg Plakette of the German Pharmacological Society, whose president, Professor Ullrich Trendelenburg, came over to Aberdeen to present the award. This was most fitting as it was the paper by Ulli's father which had first interested Kosterlitz in morphine.

He was very proud of being made a Doctor, honoris causa, of the University of Liege, and always wore the insignia over his shoulder when attending graduation and other official university ceremonies. In 1979 the University of Aberdeen awarded him the degree of LLD honoris causa. This was a most unusual honour, to recognise in this way someone still working in the university.

I am reminded of a quotation by another German pharmacologist who also made his home in the UK, who once said "How fortunate are those who can do research their whole life. For however long they live - they die young."

A.S. Milton

Hans Walter Kosterlitz, pharmacologist: born Berlin 27 April 1903; Research Worker in Physiology, Aberdeen University 1934-36, Assistant and Carnegie Teaching Fellow 1936-69, Lecturer 1939-45, Senior Lecturer 1945-55, Reader in Physiology 1955-68, Professor of Pharmacology and Chemistry 1968-73; FRSE 1951; FRS 1978; FRCPE 1981; Director, Unit for Research on Addictive Drugs, Aberdeen University 1973-96; married 1937 Hannah Gresshoner (one son); died Aberdeen 26 October 1996.