Dr. Hans Kosterlitz
A Tribute to Dr. Hans Kosterlitz
The following obituary was written by Dr. R. Alan North of Glaxo Geneva Biomedical Research Institute, a former student and colleague of Professor Kosterlitz.
Hans Walter Kosterlitz was born in Berlin on 27 April 1903. He was the son of a physician, and he himself studied medicine in Berlin. Upon graduation in 1928 he became an assistant in the First Department of Medicine at the University of Berlin, working both in clinical radiology and in biochemical research in the area of carbohydrate metabolism and particularly galactosemia.
Kosterlitz arrived in Aberdeen in March 1934; he took a research assistantship with Professor J J R MacLeod. MacLeod, who shared the 1923 Nobel prize in Physiology and Medicine for the discovery of insulin, had returned to Scotland from Toronto in 1929 to the chair of Physiology. At first Kosterlitz worked on the relationship between blood pressure and blood sugar concentration; but MacLeod died in 1935, and Kosterlitz then returned to his earlier interest in why patients with liver failure had galactosemia. This led to the isolation of galactose-1-phosphate, the first step in the conversion of galactose to glucose; the absence of the converting enzyme underlies familial galactosemia. He became medically qualified in Britain, and received the PhD (1936) and DSc (1944) from the University of Aberdeen. In 1939 he was appointed Lecturer in the Department of Physiology and remained on the faculty thereafter (Senior Lecturer, 1945 - 1955; Reader, 1955 - 1968; Professor and Head of Pharmacology Department, 1968 - 1973; Professor Emeritus and Director of the Unit for Research on Addictive Drugs, 1973 - 1996).
During the war he sought more direct application for his research and entered the area of nutrition. This led him to try to determine how diet affected the amount of sympathin (now noradrenaline) released from hepatic sympathetic nerves. The interest in the autonomic nervous system developed further during a visit to Otto Krayer’s laboratory at Harvard in 1953, in which he studied the actions of veratrum alkaloids on the heart. At about that time, Kosterlitz read a paper by Paul Trendelenburg which had been published in 1917; this described that low concentrations of opium alkaloids inhibited the peristaltic reflex on the guinea pig. It was the pursuit and elaboration of this finding which set the stage for much of his subsequent work.
He showed that morphine inhibited the release of neurotransmitters from several autonomic neuroeffector junctions, that the effect was greatest at low frequencies of stimulation, and did not result from local anesthetic action. He determined the dissociation equilibrium constant for naloxone as an antagonist of morphine in the guinea pig ileum. In a ‘blind’ experiment with compounds supplied by Maurice Seevers of Michigan he showed that the action of various opiates to inhibit acetylcholine release in the guinea pig ileum correlated very well with their effects in monkey and man. Much of this work was carried out together with Cairnie, Gyang, Lees, Lydon, Thompson, Wallis, Watt and Waterfield.
At the age of 65, Hans Kosterlitz became Professor when the new department of pharmacology was created. One of his appointees as lecturer was John Hughes, a neuropharmacologist with particular expertise in the release of noradrenaline. John Hughes joined Hans Kosterlitz when, obliged by age limitations to ‘retire’ in 1973, he established the Unit for Research on Addictive Drugs. Several features of the actions of morphine in man and isolated animal tissues (but particularly the marked selectivity of enantiomers), led them to reason that it mimicked the actions of substances that occurred naturally in the body as hormones or neurotransmitters. As it happened, Graeme Henderson (a PhD student with Hughes and Kosterlitz) had just found a further example of a morphine-sensitive neuroeffector junction in the mouse vas deferens and this was used as the principal bioassay for the isolation of the enkephalins. Such is serendipity -- the guinea pig ileum preparation probably would not have worked to follow the isolation and purification because it has too much enkephalinase activity.
The second element of serendipity, and a prepared mind, is better known. Howard Morris, who had collaborated with Kosterlitz and Hughes to identify enkephalin definitively by mass spectrometry, heard a lecture by Derek Smyth on the subject of the pituitary prohormone b-lipotropin. He noticed that the C fragment of b-lipotropin (now known as b-endorphin) began with the pentapeptide sequence of Met-enkephalin. Thus was initiated the search for all the opioid peptide precursor proteins. The discovery of the enkephalins catalyzed major new fields of research endeavour in neuroscience, physiology, pharmacology and endocrinology.
The Unit for Research on Addictive Drugs remained at the forefront of opioid research for the next 10 - 15 years, supported by the Medical Research Council of Great Britain and the National Institute on Drug Abuse of the United States. The main contributions during this time were the first distinctions between m (morphine) and d (vas deferens) receptors, elucidations of the factors determining the binding of ligands to m, d and k receptors, and studies on the release of enkephalin from nerves and its degradation in biological tissues. During these years, Kosterlitz received many awards, prizes, and lectureships. They included the Schmiedeberg Plakette of the German Pharmacological Society, the Wellcome Gold Medal of the British Pharmacological Society, the Royal medal of the Royal Society of London and the Albert Lasker award. He was an honorary member of the British Pharmacological Society and the Physiological Society, a Fellow of the Royal Society of London, and a foreign member of the U.S. National Academy of Sciences.
Hans Kosterlitz died on 26th October 1996 at the age of 93. All those who met him learned that science was tough but science was fun. Tough meant rigorous; it meant not discussing things that you did not understand. Tough meant hard work; Kosterlitz was a man of long hours. Tough meant argumentative, when an intellectual point was to be made. Fun for Hans was good company, travel, food and wine. Fun showed itself in his wry humour and the twinkle in the eye. Fun was embodied in his constant admonition to "work harder but play harder". He is survived by Hannah, indefatigable wife of almost 60 years, and beloved of the opioid research community worldwide. Hans and Hannah have one son, Michael, who is a theoretical physicist at Brown University in Providence, Rhode Island. They have three grandchildren Karin, Jonathan and Elizabeth.
Kosterlitz’s legacy is not only enkephalin; it is the INRC. At the Fourth International Pharmacology Congress in Basle in 1969, Hans Kosterlitz and Harry Collier organised a small satellite session of opiates; thus began the International Narcotics Research Club (now Conference).
The history of the development of the INRC is chronicled elsewhere, but its future will be a lasting testimony to a man who not only did science well, but loved science well, and loved the fun of communicating science.
Dr. R. Alan North