This month, Human Reproduction Update features a key article of historical importance authored by Emeritus Prof. James Boyer Brown AM, MSc (NZ), PhD (Edin), MSc (Melb), DSc (Edin), FRANZCOG (Ad Eundem) before his death on Saturday, 31 October 2009. It gives an unprecedented insight into the origins and interpretation of the measurement of reproductive steroids for clinical management of menstrual cycles, both for fertility and contraception. Prof. Brown's work revolutionized reproductive medicine by permitting accurate monitoring of ovarian activity before the days of pelvic ultrasound and led to safe and effective monitoring for ovulation induction, IVF and prediction of spontaneous ovulation.

Born on 7 October 1919 in New Zealand and educated at Auckland University College, James Brown entered the laboratories at the Auckland Hospital early in the Second World War. He rationalized the sterilization procedures at the hospital, qualified in bacteriology, haematology and histology and built up the biochemistry laboratory. 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 synthesizing or regenerating them, using techniques that often required innovative use of materials available. 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 estrogen 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. He received a National Research Scholarship to work in Edinburgh under Prof. Guy Marrian FRS, one of the early pioneers of the science underlying estrogens.

His aim was to develop a chemical method for measuring the estrogens 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 although 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 estrogen production throughout the menstrual cycle, which had been shown previously using labour intensive animal bioassays. This work led to a PhD, and The Lancet published 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.

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, they purified these hormones and later developed the International Standard Reference Preparation, facilitating their widespread use. 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 rationalize their use.

In 1962, he accepted an appointment as First Assistant in the Department of Obstetrics and Gynaecology at the University of Melbourne under Prof. Lance Townsend. This was despite many attractive offers from the USA including one from Dr Gregory Pincus, the originator of the oral contraceptive pill. In Melbourne, he showed his true genius and, in conjunction with his colleagues at the Royal Women's Hospital, he revolutionized the use of gonadotrophins for the safe induction of ovulation. He refined his method for measuring urinary estrogen, making it effectively a routine test which could be performed in a few hours, 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 his developing the threshold theory of ovarian follicle stimulation. He further modified his rapid assay method to enable urinary estrogen to be measured during pregnancy, which was used extensively by obstetricians as a test of placental function and fetal well-being during pregnancy. 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 1970, Brown gained a DSc from the University of Edinburgh and 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 John and Lynn 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 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 that takes account of these findings. Brown continued to work on various scientific projects and was involved with the World Health Organization's Special Programme of Research in Human Reproduction.

Perhaps his professional life could best be summed up by Paul McDonough in a closing editorial comment made in 2003 in response to a letter he had published in Fertility and Sterility (2003;80:677–678):

‘…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’.