The scientific and medical community mourns the loss of our esteemed colleague and good friend Emeritus Professor James Boyer Brown AM, MSc (NZ), PhD (Edin), MSc (Melb), DSc (Edin), FRANZCOG (Ad Eundem), Life Member Fertility Society of Australia, Life Member Endocrine Society of Australia, who passed away on Saturday 31st October 2009, aged 90.
Born 7 October 1919 in New Zealand and educated at Auckland University College (MSc - First Class Honours in chemistry), James Brown was manpowered to the laboratories at the Auckland Hospital early in the Second World War. He rationalised the sterilisation procedures at the hospital, qualified in bacteriology, haematology and histology and built up the biochemistry laboratory from some simple backroom tests to the type of facility that exists today. He also set up the blood bank, the monitoring of blood electrolytes and the production of sterile solutions for peritoneal lavage (the precursor of renal dialysis).
During the war, chemicals that were required for the new tests were often in short supply so he developed methods for synthesising or regenerating them, using techniques that often required innovative use of materials available. One example of his innovative skills was the production of ampoules of blood-typed sera for the Pacific forces using a home-made freezer. The ability to innovate was a skill that he used to great advantage right throughout his life and he was constantly searching for better ways of doing things.
After the war in 1947, he developed an interest in endocrinology and reproduction and started a small animal breeding surgery, set up bioassays for urinary gonadotrophins and oestrogen (the female hormone) and concluded that the most important requirement in human reproduction was the development of a highly accurate method for timing ovulation in women, similar to the phenomenon of oestrus in animals. Measurements of the oestrogens seemed to be the answer and he received a National Research Scholarship to work in Edinburgh under Professor Guy Marrian FRS, one of the discovers of oestrogens.
His aim was to develop a chemical method for measuring the oestrogens in the urine and was given a position in the newly established Clinical Endocrinology Research Unit in Edinburgh, later to be appointed its Assistant Director. Notwithstanding Marrian's attempts at dissuading him from this project, Brown persisted and the essential problems were solved within a few months but a fully validated method was not published until 1955. This published paper has been cited over 1000 times and was awarded a full Citation Classic by the Institute for Scientific Information.
Using this new method of measurement, Brown confirmed the elegant patterns of oestrogen production throughout the menstrual cycle which had been shown previously using labour intensive bioassays. This work led to a PhD and The Lancet requested the privilege of publishing the results obtained during the menstrual cycle, conception, pregnancy, lactation and return to fertility. His method was the "gold standard" for measuring these hormones for almost 20 years until superseded by radioimmunoassays on blood. He also collaborated with Arnold Klopper in developing a urinary preganediol assay in non-pregnant women which was awarded a half Citation Classic.
Possibly one of the greatest contributions made by Brown in his early days in Edinburgh was the use of human gonadotrophin for the induction of ovulation. Working with colleagues there they purified these hormones and later developed the International Standard Reference Preparation facilitating their widespread usage. The Edinburgh unit was the second in the world to use human gonadotrophins for ovulation induction in humans but Brown, later working in Melbourne, would properly rationalise their usage.
In 1962 he accepted an appointment as First Assistant in the Department of Obstetrics and Gynaecology at the University of Melbourne under Professor Lance Townsend. This was despite many attractive offers from the USA including one from Dr Gregory Pincus, the originator of the oral contraceptive pill. It was here that he showed his true genius and, in conjunction with his colleagues at the Royal Women's Hospital, he revolutionised the use of gonadotrophins for the safe induction of ovulation. He refined the his method for measuring urinary oestrogen making it effectively a routine test which could be performed in a few hours, thereby enabling these drugs to be used in a safe manner and all but eliminating the risk of high order multiple pregnancies which had been a feature of this treatment up until that time. This was the first time that this approach had been used and led to him developing the threshold theory of ovarian follicle stimulation which stands unchallenged today in reproductive medicine.
He further modified his rapid assay method to enable urinary oestrogen to be measured during pregnancy which was used to great effect by obstetricians as a test of placental function and fetal well-being during pregnancy.
During a sabbatical year in 1970, Brown gained a D.Sc. from the University of Edinburgh and delivered 63 lectures and demonstrations in Europe and the USA.
Notwithstanding the advent of radioimmunoassay, the laboratory continued to be world renowned for its urinary assays and attracted large contracts, principally from Harvard University for studying risk factors in breast cancer and from Family Health International for studying the return of fertility during breast feeding. The work with Harvard won the Prix Antoine Lacassagne from Paris as the most important contribution to the study of breast cancer for that year.