RIE - Toxicology Laboratory
When GF Marrian had been an Associate Professor at Toronto University (1933 to 1938), his research used the Kober reaction (first observed by the young Dutch chemist Kober in 1931) to measure urinary oestriol and oestrone in pregnancy. After World War II, Marrian and his colleagues in Edinburgh developed a method for measuring urinary pregnanediol and provided reliable methods for measuring steroid hormones in blood and urine. He and his colleagues presented a case to the Medical Research Council for the establishment of a "Clinical Endocrinology Research Unit" in Edinburgh. This was approved in October 1946 and the Unit was controlled by a committee comprising John H Gaddum, Professor of Pharmacology (Chairman), CP Stewart, Reader in Clinical Chemistry (Secretary), GF Marrian, Professor of Biochemistry, Robert J Kellar, Professor of Obstetrics and Gynaecology, Derrick Dunlop, Professor of Therapeutics and JR Learmonth, Regius Professor of Clinical Surgery. During the next decade or so, this Unit became one of the most prestigious hormone laboratories in the country.
Initially the CERU opened in the Clinical Chemistry Laboratory in the Royal Infirmary and then moved into the refurbished laboratory in Forrest Road (ca. 1950); previously the premises of the Royal College of Physicians Laboratory. (ref: 2)
Barbara Clayton (later to be Consultant (1959 to 1970) and Professor in Chemical Pathology (1970 to 1978) at the Institute of Child Health, Great Ormond Street, London, Professor of Chemical Pathology and Human Metabolism in Southampton (1979 to 1987) and Dame Barbara Clayton, DBE) was a Research Assistant from 1947 to 1949 working for her PhD under GF Marrian. She started this work in the Biochemistry Department Laboratories in the Medical School in Teviot Place and later moved to the laboratory in the Royal Infirmary where she was in day-to-day charge. She moved to St Thomas's Hospital, London, in 1949 and years later Sheila Atherden (Marrian's personal technical assistant) joined her as Senior Chief M.L.S.O. at Great Ormond Street, London. She died in 2011. (ref: 44, 54)
William St. Clair Bauld from Canada succeeded Clayton in 1949. Bauld had both a Medical and an honours degree in Chemistry, which was unusual at that time.
In 1949 James B Brown, a chemist from New Zealand, and John Loraine were appointed. Loraine worked on bio-assays for non-steroidal hormones (gonadotrophins). Later he was appointed as Director of the Unit.
Methods for measuring urinary oestrogens were developed by the Unit.
This involved long evening sessions and Bauld often enlisted the help of a night watchman to change tubes under a fractionation column (as no automatic tube changing device was available) while he went out to buy fish suppers. To assist with these studies of urinary oestrogen excretion, JA Owen, who had recently joined the staff of the Clinical Chemistry Department, arranged for his wife to collect 420 consecutive 24 hour urines which spanned a normal period, a pregnancy and back to a normal period again.
Only two specimens were lost; one met with an accident in the laboratory and the other was spilt on a Corporation bus (while being taken to work by Owen). This collection period may be a record for a normal volunteer. Eveline J Roy (later Eveline J Harkness), one of Brown's PhD students, successfully applied the method for urinary oestrogens to the measurement of blood oestrogens.
Bauld returned to Montreal, Canada, in 1954 and in 1958 he, his wife and two of their four children died in a car crash in New Brunswick. Brown left in 1962 to continue his work in Melbourne University, Australia, where he was recognised with a personal chair. (ref: 2, 39, 44, 47, 113)
In 1952 Arnold Klopper was appointed to the Unit. He, with Eileen Michie, produced an improved method for urinary pregnanediol. Klopper later became Professor of Reproductive Endocrinology at Aberdeen University.
The methods for monitoring gonadal function which were developed and applied by the CERU formed the basis for much of modern reproductive medicine and it is a measure of the success of the Unit that many other laboratories, research and routine, were set up throughout the U.K. to perform similar studies. Over the years, a difference of emphasis became apparent between the CERU and the Department of Clinical Chemistry. The experience of the latter suggested that readily available hormone determinations, even if not totally specific, were more valuable to the clinical staff than the isolated measurement of a single hormone undertaken by professional research workers and reported on weeks, if not months, later.
In the late 1950s, CP Stewart demitted office from the Unit and a new committee took charge of the Unit. John A Strong, a Consultant Physician at the Western General Hospital, Edinburgh, and later Professor of Medicine, was appointed as secretary/administrator. He, Marrian and Sir John Bruce, Professor of Surgery, had developed an interest in the treatment of breast cancer. Marrian's interest in the endocrine aspects of this condition centred on the application of the reliable methods which had been developed for oestrogen assays. Marrian joined the Imperial Cancer Research Fund in 1955 and soon became Chairman of its Research Advisory Committee. In 1959, he was appointed as Director of the new Imperial Cancer Research Laboratories which were being built at Lincolns Inn Fields, next to the Royal College of Surgeons, London. He retired in 1968 and died in 1981.
The range of the work broadened during the 1960s. The group from the Clinical Chemistry Department at the Royal Infirmary which had been working on steroids in the foeto-placental unit and the new-born moved to the CERU when FL Mitchell was appointed to the Clinical Research Centre in Northwick Park, Harrow, in 1964. (ref: 80)
Klopper was succeeded by Ken Fotherby, who worked on the isolation and identification of urinary steroids, and then by R Angus Harkness, who introduced a testosterone assay to the spectrum of available methods.
Harkness left in 1966 to take up the post of Consultant at the Edinburgh Royal Hospital for Sick Children and, in 1976, was appointed to the M.R.C. Clinical Research Centre, Northwick Park, Harrow. There he demonstrated that intracellular ATP could be monitored extracellularly by concentrations of the purine base hypoxanthine in available body fluids, including CSF and amniotic fluids. During the closure of the MRC Clinical Research Centre he moved to an appointment at the Institute of Child Health, Great Ormond Street, London, from which he retired in 1990 (ref: 2, 47, 147)
Eduardo Menini continued to show ingenuity in evolving methods for the systematic analysis of urinary steroids, Ken Hooper worked on peptidases, Keith Kirkham worked on thyroid hormones, Bill M Hunter generated a series of radioimmunoassays and Pat Stevenson worked on cellular biochemistry. During this time drugs were being studied which are now used routinely to modify gonadal function. The M.R.C. retitled the Unit "Reproductive Biology" and Roger Short added his broad and original interests, especially in animals, to the continuing themes of work. (ref: 47)
Bill Hunter developed the first practical radioisotope labelling techniques for proteins and, thus, was one of the founding fathers of modern RIA. When he was in charge of the MRC Unit, he developed one of the world's first RIA autoanalysers using sucrose separation. He left around 1979-80 to see his instrument into production. Euan Cameron worked with Hunter in the 1970s before moving to take charge of RIA QC for Amersham in Cardiff. (ref: 158)
Royal Hospital for Sick Children - Edinburgh
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