William Drummond Macdonald Paton, pharmacologist: born Hendon, Middlesex 5 May 1917; staff, National Institute for Medical Research 1944- 52; Reader in Pharmacology, University College London and UCH Medical School 1952-54; Professor of Pharmacology, Royal College of Surgeons 1954-59; FRS 1956; Professor of Pharmacology, Oxford University, and Fellow of Balliol College 1959-84 (Emeritus); CBE 1968; Chairman, Committee for Suppression of Doping 1970- 71; Chairman, Research Defence Society 1972-78; Kt 1979; Hon Director, Wellcome Institute for History of Medicine 1983-87; married 1942 Phoebe Rooke; died Oxford 17 October 1993.
THE FIRST effective treatment of high blood pressure, the facilitation of artificial respiration in an intensive care unit and the exploitation of oil and gas from beneath the North Sea: these are but three recent benefits from basic research in pharmacology and they all come largely from one man, William Paton. Paton was one of the world's great pharmacologists, a man in whom were combined a remarkable intellect, great practical skill and a warm personality.
To some, Paton appeared to be the archetypal Oxford don, oblivious of the world around him and obsessed with knowledge for its own sake. How, then, did he make discoveries that were to have such an impact on mankind? The secret lies in his mind, for here was an incisive, clear and uncompromising brilliance that could cut through complexity and bring order out of confusion.
The first great discovery, made in 1949 with E. Zaimis, was of beautiful simplicity. Two different actions of the chemical neurotransmitter acetylcholine, that cause muscles to contract and that cause an increase in blood pressure (through activation of sympathetic ganglia), could be separated by means of two antagonist drugs that differed only in the number of carbon atoms in a linear chain. Thus, we have decamethonium, with 10 carbon atoms, the first specific neuromuscular blocking drug and the father of all modern drugs used in surgery as muscle relaxants, and in intensive care to permit artificial ventilation. Hexamethonium, with six carbon atoms in the chain, was the first drug that specifically and safely lowered blood pressure.
The number of people who have directly benefited from drugs in these two classes must by now run into millions, and yet the discovery was not driven by the need to develop such drugs, but by intellectual curiosity. Both classes of drug act on receptors for acetylcholine on cells, but, at the time they were discovered, the concept of the drug receptor was not universally accepted - Paton's work provided dramatic evidence of such specific sites where drugs act on cells. It was only with the advent of molecular biology in the 1970s that his concept of the two types of receptor, one in muscle and one in ganglia, was confirmed directly.
The second discovery concerned the cause of the changes that happen to deep-sea divers as they go deeper, leading to convulsions and death. The discovery had a long gestation, for Paton's interest in the problems of diving was stimulated during the Second World War, when he went to work in the National Institute for Medical Research, but it was not until he came to Oxford in 1959, and started to collaborate with physical chemists, that a solution was found.
For a long time, divers were limited to working at depths of no more than 200ft below sea-level, because of the risk of convulsions. It was thought that the convulsions were due to the narcotic effect of the gases (oxygen and helium) at high pressure, but Paton and his colleagues discovered that the cause was the high pressure itself, hence the term 'high pressure neurological syndrome'. At about the same time they were also studying the remarkable phenomenon of the ability of high pressure to reverse the anaesthetic effect of the gases.
In an imaginative leap typical of Paton the question was asked: if high pressure could reverse the biological effects of anaesthetics, could anaesthetics reverse the biological effects of high pressure? Thus was born the idea of adding a third gas to the mixture that divers used, a gas (nitrogen) that was not an anaesthetic at normal pressures but that became an anaesthetic at the high pressures needed for deep dives. The resulting mixture of oxygen, helium and nitrogen (the so- called Tri-mix) is now used throughout the world and has enabled divers to work at depths of around 2,000ft. Without Tri-mix, it is difficult to imagine how gas and oil could have been recovered from under the North Sea, and from many other similar sources throughout the world.
These are but two discoveries made by Paton - pharmacologists know him for many more - but they illustrate how simple curiosity, coupled with imagination and a penetrating mind, can yield unexpected dividends to mankind.
It is sobering to realise that Bill Paton combined his scientific work with an amazing appetite for public service: he was at one time the member of 72 committees, several of which he chaired. After a brilliant undergraduate career at Oxford (three prize scholarships) and at University College Hospital Medical School (Gold Medallist), he succeeded to the chair of pharmacology at Oxford in 1959 and quickly became sought after for his advice by government, and for his incisive judgement by bodies such as the Clarendon Press, Rhodes Trust, Wellcome Trust and the Council of the Royal Society. He had a special interest in the history of medicine and was Honorary Director of the Wellcome Institute for History of Medicine from 1983 to 1987. His awareness of the social responsibility of science led him to be Chairman of the Research Defence Society and to write a scholarly, witty and important book, Man and Mouse: animals in medical research (1984). The expanded second edition, which Paton had extensively revised, was published this year.
For those fortunate to work close to him, Paton was a deeply inspiring and yet approachable colleague who gave sympathetic advice, often with a delightful sense of humour. I was fortunate to be both a graduate student and then lecturer in his department at Oxford and perhaps there was one lesson above all that I learnt from him: to try to be accurate in everything. Bill Paton realised that accuracy is something that scientists should learn from their earliest work but also that it need not be restricted to measurement. In a complicated situation, as he wrote, 'if one simply tries at the start to make as accurate a description or diagnosis or account as possible, it can release a cramp. Everyone respects accuracy; and once the initial ground is clear, solutions become easier to find.'
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