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This section is written to support the authenticity of the studies
reported here and to show that they are part of the mainstream of
research in human
reproduction. Historically, mainstream research in reproduction
and its publication have been dominated by the aim of halting the
world population
explosion and more recently by the expectation that the main aim
of the research is to make profits. Natural family planning (NFP)
has not been seen
to fit in with either expectation and thus funding for research
and the ability to publish the findings have not been in proportion
to the importance of the
research. Furthermore, drug companies are important providers of
funds. James Brown has had his share of grants and, in addition,
has been
fortunate in being able to earn through his laboratory enough to
fund the other projects which he has thought important. Also, as
he has made the
advances, the routine applications have usually been taken over
by others and this has freed him to move on to new challenges. Application
of the
mucus symptom is the one exception. This has been resolutely rejected
by his clinical colleagues, the reason being a complete mystery.
He believes
that achieving the full potential of NFP is the greatest research
challenge in human reproduction today and that the Billings Ovulation
Method is the
nearest to achieving this aim.
James Brown's interest in reproduction began in the 1940s in New
Zealand when he observed the rapid progress being made in animal
reproduction at
the time. This progress was made possible by understanding the phenomenon
of oestrus which enabled the fertile time of the animal ovarian
cycle
and ovulation to be determined with precision (oestrus causes the
female to accept the male only at the most fertile time of the cycle).
He reasoned
that an equally accurate method for timing ovulation in the human
would allow the same progress to be made. Furthermore, as Nature
uses the
interaction between oestrogen and progesterone produced by the ovaries
to manifest oestrus, measurement of these hormones was the most
likely
method of achieving his aim. Consequently he joined the research
team in Edinburgh of Professor Guy Marrian who was one of the men
who isolated
and characterized the oestrogens. During the 1950s the team was
successful in developing methods for accurately measuring the metabolites
of the
oestrogens, progesterone and luteinizing hormone in urine and, for
the first time, documented the precise patterns of these hormones
throughout the
fertile ovulatory cycle and related these patterns to ovulation
and fertility.
Having established a reputation in the field, James Brown has been
involved in practically every major development in human reproduction
since then
until his retirement in 1985. He was a member of Dr Gregory Pincus's
think-tank for the development of the oral contraceptive pill and
performed the
early work on its action. He was surprised that the pill was so
quickly and universally adopted by women without an adequate study
of its safety and
possible long-term effects. At the same time he was pioneering work
on assisted reproduction including the use of timed intercourse
(as used by
Nature in the phenomenon of oestrus) and clomiphene and human gonatrophin
for women with deficient ovarian activity. The Swedes won the race
to be the first to use human gonadotrophin but reported a startling
multiple pregnancy and hyperstimulation rate.
In 1962 James Brown joined the Department of Obstetrics and Gynaecology,
University of Melbourne. With colleagues, he developed methods for
the safe use of human gonadotrophin with the minimum of multiple
pregnancies, and for a time produced all the gonadotrophin for clinical
use in
Australia, New Zealand, Singapore and parts of Canada. From the
clinical results, he developed the incremental system of gonadotrophin
therapy and
propounded the threshold hypothesis of gonadotrophin action on the
ovary. The threshold hypothesis explained, for the first time, how
only one follicle
is usually selected for ovulation in the human, but it took 20 years
for the explanation to be universally accepted. The pregnancy rate
achieved with
gonadotrophin therapy has not been bettered. The key to this success
was in mimicking the hormone patterns of the natural cycle as closely
as
possible, a point which is still not fully appreciated today. He
has continually improved the sensitivity, speed and convenience
of the methods for
measuring oestrogen and progesterone metabolites in urine, so that
the lowest concentrations found in the human can be measured. In
the early
1970s, the rest of the world changed to blood assays for monitoring
ovarian and pituitary activity. The validation of these blood assays
depended on
demonstrating that the hormone patterns obtained were the same as
those obtained by the urinary assays.
With infertility due to anovulation now fully treatable, James
Brown joined Professor Carl Wood's team which was developing in
vitro fertilization
(IVF) for achieving pregnancy in women with occluded fallopian tubes.
During the next 7 years he provided the expertise for timing egg
pick-up for
IVF and also was the optimist that success would ultimately come.
His methods for timing egg pick-up were also used for achieving
the first IVF
pregnancy in Britain. Although he is one of the "fathers"
of IVF in Melbourne, he is critical of some of the bizarre applications
of IVF, of some of its
subsequent developments and its low pregnancy rates.
Other interests include research on hormone-dependent cancers,
notably cancers of the breast, endometrium and ovaries. As much
time has been
devoted to cancer research as to reproduction. Studies were conducted
during the 1950s on the effect of endocrine ablation as a treatment
for breast
cancer. Later, with colleagues at Harvard University, a large international
study was conducted on risk factors in the development of breast
cancer.
This work was awarded the Prix Antoine Lacassagne from Paris in
1986 as the most important contribution to the study of breast cancer
for that
year.
James Brown met Doctors John and Evelyn Billings in 1962 and immediately
appreciated the rightness of their findings and aims. The research
that
followed and the way it fitted in with his other studies is described
in this booklet. As blood is not suitable for the serial assays
required for long-term
monitoring of ovarian activity, particularly at home, and his laboratory
was apparently the only one in the world which was able to perform
the urinary
assays, he has spent his latter years developing the Home Ovarian
Monitor. This system utilizes urine, it is simple enough for women
to measure their
hormone production at home, it can be used by assisted reproduction
clinics to maintain daily control of their treatments and anyone
can use it to
check the statements made in this monograph. As a final note, the
quest for the equivalent of the phenomenon of oestrus in the human
is now ended;
it is contained in the concepts of the Basic Infertile Pattern (BIP),
the oestrogen rise (ER) and the progesterone change (PC) which have
come from
the work of John and Lyn Billings.
Some Recognition for this Work
1952 Ph.D. Edinburgh; 1958 American Cancer Society Fellowship; 1961
Lecture, Laurentian Hormone Conference, U.S.A.;1970 D.Sc. Edinburgh;
1971 Professor (personal chair) Department of Obstetrics and Gynaecology,
University of Melboume;1978 Senior Organon Prize (with Henry
Burger); 1981 Fellow, Royal Australian College of Obstetricians
and Gynaecologists ad eundum;1983 Citation Classic, the seventh
to be awarded to
a worker in Melbourne; 1986 Professor-Emeritus, University of Melbourne,
Life Member of the Australian Endocrine Society and of the Fertility
Society of Australia.
Publications
Approximately 230 publications in refereed scientific journals
and chapters in books.
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