Obituary: Professor James Boyer Brown

MELBOURNE, Australia -

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.

In 1971 he was given a Personal Chair in the Department of Obstetrics and Gynaecology at the University of Melbourne and was a member of the IVF team led by Carl Wood. His work and understanding of ovarian function has been linked to the development of the early techniques for egg pick up in IVF and were used in the first successful IVF pregnancy in Britain.

Brown retired from the University in 1985 and was accorded the title of Emeritus Professor. Nonetheless he continued to work in the field. He had established in 1962, a close working and personal relationship with Drs John and Lyn Billings who developed the concept of fertility recognition through the changes in cervical mucus secretion, forming the basis of Natural Family Planning. He validated their findings and continued to work closely with them especially in his latter years when he developed the Home Ovarian Monitor - a kit that can be easily used at home even by those without any laboratory training, to check their hormonal status. This was a quantum leap from his early methods where one fully trained worker could do only 10 assays per week! Working with the Billings, the availability, simplicity and low cost of this facility has enabled him to study literally hundreds of thousands of cycles in women in various stages of their reproductive lives and develop a theory of ovarian function which takes account of these findings.

Right up to the time of his death Brown continued to work on various scientific projects and was involved with the World Health Organisation’s Special Programme of Research in Human Reproduction.

Perhaps his professional life could best be summed up by a closing editorial comment made in 2003 in response to a letter he had published in Fertility and Sterility, the Journal of the American Society for Reproductive Medicine:

“…In these days of hype, grossness and glitz, Dr Brown is a model of scientific practice who is even more imposing by the low profile that he has been able to keep over the last two decades. Perhaps these are the ideals and values for which we need to renew our subscription.”

McDonough, P. Fertility and Sterility 2003; 80, (3): 677-678

James Brown is survived by his wife Wendy and their four children.

Prizes and awards

1958 American Cancer Society Fellowship

1970 Runner-up in award for having made the most important contribution in endocrinology in the British Commonwealth

1978 Senior Organon Prize (joint winner with Henry Burger)

1981 Lecture Laurentian Hormone Conference USA

1981 Fellow (Ad Eundem) Royal Australian and New Zealand College of Obstetricians and Gynaecologists

1986 Prix Antione Lacassagne, Paris, in conjunction with Harvard colleagues

2003 Member of the Order of Australia (AM) “for service to clinical research into women’s health and reproductive issues and the development of the Home Ovarian Monitor”.

For more information and interviews, contact: Dr Adrian Thomas Billings Life Australia +61-3-9802-2022 www.woomb.org Image Attachments Links: asianetnews.net/view-attachment?attach-id=139650

Source: Ovulation Method Research and Reference Centre of Australia Ltd

Dr Adrian Thomas of Billings Life Australia, +61-3-9802-2022