FREDERICK ('ERIC') RANDALL SMITH Bsc, Phd(Edin), FRSC Eric
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FREDERICK ('ERIC') RANDALL SMITH BSc, PhD(Edin), FRSC Eric Smith was responsible for research activities in Duncan Flockhart Ltd, T & H Smith Ltd and Edinburgh Pharmaceutical Industries Ltd during the period 1947 to 1971. He and his colleagues made several lasting contributions to medicine and commerce notable amongst which were the creation of a new opiate industry based on large scale poppy growing in Australia, the establishment of dihydrocodeine ('DF118') as a major analgesic, and the discovery of 'Bitrex', an intensely bitter substance, now a widely used denaturant. He was elected a Fellow of the Society in 1962 and served on Council 1969-71. Born in Edinburgh on April 4th, 1911, Eric spent his childhood, his school and university days, and most of his working life and retirement in or near to the City. He died there on November 4th, 1994. Eric's enquiring attitude to life owed much to his father. This unusual man earned his living in the Actuarial Department of the Scottish Provident Institution but his main interests were astronomy and art. He was an FRAS and his personal observations led to his name being given to a minor lunar crater, and a good enough artist for his works to be hung in the Royal Academies in Edinburgh and London. Perhaps this is why Eric chose to be a scientist and his sister an art teacher. Eric was educated at the Edinburgh Institution (later named Melville College) where he was an excellent scholar and a good enough sportsman to play for the 1st XV and the FPs. He was Head of School in 1928 -29. Eric had a life-long interest in the school and his three sons and two of his grandchildren followed him there. Influenced by Ernest Sparham, a skilful science master, Eric entered Edinburgh University in 1929 to study chemistry and graduated BSc with first class honours in 1933 and PhD in 1935. His PhD supervisor was Dr H G Rule whom he admired as a teacher of organic chemistry. Together they devised a new synthesis for dibromoanthanthrone which ICI Dyestuffs Division adopted to manufacture Caledon Brilliant Orange RS. More important for Eric, however, they also recruited him in 1936 to work in their process development laboratories. Eric was fortunate that the Dyestuffs Division was about to be the cradle of ICI Pharmaceuticals Division which eventually grew into Zeneca Pharmaceuticals Ltd, the major component of Zeneca plc. The driving force for the change was imminence of war with Germany and the need for independent sources of supply for the major medicines imported from that country. Eric worked at Huddersfield and Blackley on established medicines and on original ICI inventions such as the long-acting sulphonamide, sulphamezathine. After the war he built on this pharmaceutical experience and returned to Edinburgh in 1947 as Chief Research Chemist with Duncan Flockhart Ltd. This old pharmaceutical business had supplied chloroform to Sir James Simpson a century earlier and, unfortunately, was still largely dependent on antiquated products. Duncan Flockhart management were well aware that research-based products were changing their industry and knew that their survival required modern products. Their decision to conduct original research and to license suitable new products was, therefore, laudable but what they had to spend was too little and too late. Eric's mission to transform the company with 30 scientific staff was quite impossible. Nevertheless, he and his team achieved much of lasting importance during the next 25 years. He chose to focus on anaesthetic practice because of Duncan Flockhart's reputation in this area, and his first product was an injection containing d-tubocurarine, a muscle relaxant used during anaesthesia. He also acquired a licence for the promising new local anaesthetic lignocaine (Astra's 'Xylocaine'), a deal that would have a surprising outcome. In 1949, Eric left Duncan Flockhart to join T&H Smith Ltd, another old Edinburgh company, which was more stable because of its substantial opiate business. Within a year, however, T& H Smith acquired Duncan Flockhart and later J F Macfarlan and Co Ltd and the resultant merger was called Edinburgh Pharmaceutical Industries Ltd. Eric became its Research and Development Director with a staff of about 60. Following the merger, the new company expanded its search for new medicines. Work on tropine derivatives, recommended by Professor F S Spring, FRS, yielded trophenium, a short-acting hypotensive agent, and tigloidine, a treatment for Huntington's chorea. A search for a better local anaesthetic based on lignocaine led to the serendipitous discovery of 'Bitrex' when Eric tested a benzoyl quaternary lignocaine analogue for local anaesthetic activity by placing a small crystal of it on his tongue. It was a memorable experiment because it took more than a day for its intensely bitter taste to fade. 'Bitrex', the most bitter known substance, is widely used as a denaturant of alcoholic solvents and many other products. Controlled clinical studies on dihydrocodeine, a well-known opiate, led to its introduction as the analgesic, 'DF118' which is now a standard treatment for moderate and severe pain. However, Eric's group also tackled more visionary projects amongst which was an effort to inhibit neuraminidase, an enzyme which is essential for the spread of influenza virus in its host. The project failed but the objective was sound. The problem has recently been solved by Dr Peter Colman and his colleagues in Australia who determined the absolute structure of the enzyme by X-ray crystallography, and then tailor-made inhibitors which seem likely to transform the treatment of influenza infections. The core business of the Macfarlan and Smith companies for more than 100 years was the manufacture of alkaloids derived from opium and their leading position in the trade was the result of meticulous development work to maximise the yield of morphine from the opium and the efficiency of its conversion to codeine. In 1948, however, the companies agreed to carry out a joint exploratory programme to make morphine and related alkaloids from opium poppies grown in England. Mr Stephen King, an Oxford botanist engaged in 1951 as the responsible agriculturalist, played the leading part in the project but he was ably supported by scientists in Edinburgh who carried out thousands of assays on individual poppy capsules and devised efficient extraction methods for the alkaloids. King and his colleagues solved many difficult problems before they established a new industry based on large scale cultivation of specially developed strains of opium poppy in Tasmania. Chemical processing of the harvested dry capsules is done in Australia. King received a well-earned OBE for his part in the project. The following is his assessment of Eric Smith's contribution: '. we are all grateful for what he did to establish the poppy industry with us in Tasmania. I always had all the fun and Eric had to make the decisions. It was 19 years from the time poppy straw was on the agenda until we started manufacturing in Australia. That was a long time to have faith in a project. It was really Eric who first believed it was worth carrying out a reconnaissance in Australia in 1959 and then when we were out together in 1964 he took the decision to give Tasmania the chance of the industry. It is not easy to be long-sighted when there are annual costs and no returns. Eric always looked for all the data before making any decision and in the poppy project there were very many unknowns. It would have been much easier to say it all looks too risky, but the industry is now well established and an on-going memorial to Eric and the other Directors of Macfarlan Smith'. Edinburgh Pharmaceutical Industries Ltd joined Glaxo Group in 1964 and, under a scheme of rationalisation, research in Edinburgh was phased out. Eric remained in charge of development activities and gave special attention to the poppy project in Australia which went commercial in 1970. He chose to retire early in 1971 and settled with his wife Lucy in Granthouse where they restored an old cottage and established a varied garden. Eric had married Lucy Evelyn Topping in 1938. She was a fellow student in Edinburgh, a bacteriologist who graduated PhD in 1936 and then lectured in the Edinburgh and East of Scotland College of Agriculture. She was the gardening expert in the family who struggled with the elements to create a fine garden on the slopes of Arthur's Seat and still beautifies neglected corners of Haddington with her plantings. Eric and Lucy had three sons and one daughter during their long happy marriage. After retirement Eric severed most of his connections with chemistry and industry but maintained an active interest in the RSE where he opposed the concept that it become an 'Academy of Arts and Science' rather than the purely scientific and technological body it had always been. He also retained his interest in local affairs, for example, by serving as Chairman of a Community Council, and, above all, his interest in wild life and the environment. Eric Smith, a quiet, courteous Edinburgh rationalist, led a life of dignity and achievement He is remembered by all who knew him. I am grateful to Messrs Peter Mackenzie and Ken Reid, former colleagues of Eric in Edinburgh Pharmaceutical Industries Ltd, for access to details of that company's history and activities. DAVID JACK .