Medical Research Perspectives
The TVW Telethon Institute for Child Health Research
The birth and growth of a research institute
Fiona Stanley
Diverse research workers, variously funded by public and private
sources, were drawn together to create an Institute and an
opportunity to work together on the complex problems in child health.
MJA 1998; 169: 630-633
Introduction -
Research origins -
Rationale for a multidisciplinary institute for child health research -
Growth -
Successes -
Threats -
References -
Author's details
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More articles on Aboriginal health
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Introduction
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In 1967 two men shared a game of golf and a vision for research to improve
child health. Sir James Cruthers, then Managing Director of Channel 7
(TVW, Perth), suggested to Jim Clarkson, then the Chief Executive
Officer of the Princess Margaret Hospital for Children (PMH) in
Perth, the concept of a "Telethon" to raise money from the community
for research at PMH. The Telethon became an annual event and in the
first year raised funds for the PMH Children's Medical Research
Foundation, which funded two small hospital research groups: a
clinical immunology research unit founded by Dr Keven Turner, an
immunologist from Adelaide, and a clinical nutrition research group
established by Dr Michael Gracey, a paediatric gastroenterologist
from Melbourne with a special interest in Aboriginal children and
their health.
From these beginnings, the TVW Telethon has gone on to fund a range of
medical research in Western Australia, ultimately providing the
essential infrastructural finance for the Institute for Child
Health Research, established in 1990 and now a vigorous
multidisciplinary research centre employing nearly 200 people. The
Institute's name acknowledges not only this beginning but the
continuing support from the TVW Telethon. Sir James Cruthers has only
recently stepped down from the Institute's Board of Directors.
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Research origins
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The first two research groups funded by the Telethon were based at PMH.
In the 1970s, the immunology group was beavering away, almost in
isolation, in the neglected area of mucosal immunology, looking
particularly at the developing respiratory tree and what role the
immune system might play in allergy and asthma. This area of
immunology and cell biology has now become of global importance in
attempts to explain the epidemic of asthma and allergy sweeping the
Western world. The work of Patrick Holt was particularly
important at the time and has continued to be pre-eminent in the study
of the development of allergic sensitisation and asthma.1,2 Meanwhile, I had been fortunate enough to be awarded a National Health
and Medical Research Council (NHMRC) overseas training fellowship
in epidemiology at London University and at the National Institutes
of Health, USA. When I returned to Perth in 1977, I used the $4000
setting-up grant in the last year of my fellowship to establish the
Western Australian Cerebral Palsy Register (the only other
registers at that time were in Sweden and Denmark) and the first
congenital malformations register in Australia (funded by the
Commonwealth Government in the wake of the Agent Orange scare). Then,
as Senior Medical Officer in Child Health for the Health Department of
Western Australia, I and my colleagues developed statewide links
with midwives and child health nurses which laid the foundations for
the Maternal and Child Health Research Data Base. This
population-based, record-linked database has become the best in
Australia (and probably the world) and now underpins much of the
epidemiological work of the Institute.3 They were great days, as
there was so little going on in maternal and child health epidemiology
in Australia and we felt like pioneers!
In 1980 these databases moved with me into a new NHMRC Unit of
Epidemiology and Preventive Medicine at the Queen Elizabeth II
Medical Centre, and spawned a range of epidemiological studies
describing maternal and child health in WA and testing a range of
hypotheses, focusing on birth defects, cerebral palsy and low birth
weight. Telethon grants in the 1980s funded the Cerebral Palsy
Register for nearly 10 years and a case-control study of dietary
folate and neural tube defects as well.4,5 We commenced our work in
indigenous maternal and child health and employed Aboriginal health
workers in research before others had considered it important. The
resulting partnerships with Aboriginal communities have grown even
stronger since the Institute was established.
Towards the middle of the 1980s I sensed that only by collaborating
with basic scientists were epidemiologists ever going to get at
biological mechanisms, properly elucidate causal pathways and be
able to develop effective preventive strategies. Telethon funds
appeared less secure at this time as they were being given away to other
causes. I discussed these problems with Professor Lou Landau, who in
1984 had just accepted the Chair in Paediatrics in Perth, and we began
to think of setting up an institute of child health research at the
Children's Hospital, taking those with NHMRC funding with us, trying
to get some additional funds for infrastructure and solving complex
diseases! We both thought it a wonderful idea and invited Sir Gus
Nossal across from Melbourne to address the hospital on "The birth of a
research institute" -- this inspiring lecture was given in 1985 and
aroused interest among local people in the concept.
By this time Dr Wayne Thomas (from the Walter and Eliza Hall Institute
in Melbourne), Dr Geoff Stewart (from the United Kingdom) and Dr
Ursula Kees (from Switzerland) had all joined the Clinical
Immunology Research Unit at Princess Margaret Hospital, and most of
them now had "secure" NHMRC funding. Ursula Kees' group worked
closely with the oncologists in the hospital, particularly Dr
Michael Willoughby, the head of the oncology unit, who was determined
that the Children's Cancer and Leukaemia Foundation would provide
some secure funding for her laboratory in the new Institute. He could
see this was crucial to the success of better identification of
childhood cancers, investigating aetiology and discovering new
therapies.
Were we mad? We planned to set up a world-class institute in an isolated
city in the biggest but most deserted State in Australia, in the middle
of the crisis over business and political corruption known as "WA Inc"
and as a recession was in full swing. We invited a group of Australia's
leading researchers to Perth in 1986 and asked them to interview all of
the researchers in child health and make an assessment. Despite the
difficulties, the committee felt we had the right ingredients and
encouraged us to go ahead. With the support of the Princess Margaret
Hospital Board, and particularly of Professor Lou Landau, the
proposal was developed further.
In 1989, encouraged by Sir Gus Nossal, I applied for and was appointed
Director of the new Institute. In 1990 we moved into our building -- the
old School of Nursing at PMH, which was renovated with donations from
the WA Lotteries Commission and the Incorporated Body of PMH. The
support from other groups like the Variety Club of WA and the community
has been the most crucial aspect of our success in this whole venture.
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Rationale for a multidisciplinary institute for child health
research
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The problems in child health are now complex -- epitomised by diseases
such as asthma, birth defects and other developmental problems,
cancers and psychosocial problems. These stem from a complicated
series of interactions between genes and environment, with variable
causal pathways demanding complex solutions for their management or
prevention. Our thinking was that if we brought together scientists
from different disciplines under one roof we might be able to unravel
the causes more successfully than working away separately in our
little research areas. The aims of the Institute were to describe the
burden of diseases in children and families in WA, to seek causal
pathways using all types of scientific methods, and then to apply any
knowledge to prevent disease in the community or to improve treatment
at the bedside.
We started as 90 scientists in four separate groups in 1989, with
little infrastructure support, although our research grants from
the NHMRC and other local foundations were adequate. Cell Biology,
Molecular Biology and Cancer and Leukaemia moved in under the
direction of Patrick Holt, Wayne Thomas and Ursula Kees,
respectively, from the old PMH Children's Medical Research
Foundation. My group from the NHMRC Unit moved to form the Division of
Epidemiology and Biostatistics. Research in all these groups has
blossomed at the Institute.
Ursula Kees' group is making a seminal contribution on the role of
homeobox gene malfunction in childhood leukaemia and has, in close
collaboration with the PMH Oncology Unit and the international
Children's Cancer Group, made significant contributions to the use
of genetic markers to determine the prognosis and treatment for
children.6,7Wayne Thomas's
group is best known for its detailed work on the structure and
immunology of house dust mite allergens, and a molecular
approach to developing new types of immunotherapy8,9and
the development of a candidate vaccine for all types of
Haemophilus influenzae based on a conserved outer membrane
protein.10 Patrick Holt's group has
continued to describe the immunological mechanisms which operate
during the development of tolerance to inhaled antigens,11,12 which are
of extreme interest to both fundamental immunologists and
allergists alike.
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Growth
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1992 was the year of recruitment! We conducted an international
search for a top biostatistician, which paid off with the recruitment
of Dr Paul Burton, who became the Institute's senior
biostatistician, and his wife, Dr Jenny Kurinczuk, an outstanding
perinatal epidemiologist with a special interest in reproductive
issues. Dr Burton conducted theoretical biostatistical research in
a range of analytical problems (such as the analysis of complex
interacting data sets and new methods of randomised trials),
supported much of the biostatistical needs of the Institute and
of our collaborators and spearheaded our new endeavours in genetic
epidemiology. Within two years he became head of our new Division of
Biostatistics and Genetic Epidemiology.
Also in 1992 we sought an outstanding clinical researcher to
establish a new Division of Clinical Sciences, with the brief of not
only doing research in the Institute bridging the basic and clinical
sciences, but also being a role model and stimulus for clinical
research on the PMH campus. Dr Peter Sly was lured from Melbourne by
offering him "fame and poverty" (he still has the letter) and he has
continued to be a great success, collaborating with many groups in the
Institute, the hospital and with fetal physiologists and
respiratory researchers locally and internationally.
In that year as well we were extremely fortunate in convincing the
Health Department of Western Australia to second to us two
outstanding clinical psychologists, Dr Steve Zubrick and Sven
Silburn, whose research has underpinned the State Policy on Youth
Suicide and other strategies in child and adolescent mental health.
Dr Zubrick became head of the new Division of Psychosocial Research,
with Silburn his very able deputy.
The arrival of Australia's first MacFarlane Burnet Fellow,
Professor Colin Sanderson, whose work on interleukin-5 was
recognised internationally, created our last new division
(Molecular Immunology) in 1994. This was an important bit of the
jigsaw in our multidisciplinary attack on the complex disease of
asthma. Dr Dierdre Coomb also arrived and established a laboratory
specialising in the extracellular matrix, adhesion molecules and
the mechanisms of inflammation, metastasis and haematopoiesis.
As I look back now, some of our recruitment was part of a grand plan and
some, as you would understand if you were in such an isolated and remote
community, was opportunistic. Whatever the reason, the resulting
mix has worked, as shown by our growth (from less than 50 to nearly 130
research staff in eight years), the way that many groups are
collaborating in the Institute and the output to meet our goals.
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Successes
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A major reason for our success in fundraising from the local business
community was that our research was focused on health problems that
were well known as major burdens to the community -- asthma,
adolescent suicide, birth defects, cerebral palsy, cancers and
Aboriginal health. Another major factor was that we have had
significant success in translating results into action (see Box);
examples include the research on folate and spina bifida, reducing
suicidal behaviours, improving outcome following bone marrow
transplants in children with leukaemia, influencing the uptake of
Haemophilus influenzae type b vaccination (which virtually
eradicated the disease) and establishing a successful maternal and
child health program for Aboriginal families in Kalgoorlie. Most of
these are national and international issues and our Institute is
increasingly being seen as a source of information for government and
a model of success in multidisciplinary research and in translating
research into policy.
So, eight years on, have we been successful? How do you measure success
in a multidisciplinary Institute? At the end of the first year of
operation (June 1991) the Institute had $1.4 million in
peer-reviewed grants, with a total operating revenue of $3 million
(which included ongoing refurbishment costs). By the close of 1997
the Institute had gained $5.9 million in grants (including $2.5
million in NHMRC funding) and a total operating revenue of $8.3
million.
You cannot force groups of different disciplines such as immunology
and epidemiology and biostatistics to work together; all you can do is
recruit thoughtful and good scientists and put them next to each other
and hope that they talk! I remember two episodes vividly -- Patrick
Holt saying "we have a great hypothesis we have developed in the lab and
we need you epidemiologists to test it out for us"; this spawned our
multidisciplinary asthma cohort study with Patrick Holt, Paul
Burton, Peter Sly, Anne Read and myself testing the hypothesis that
early and repeated infections may influence the immune response away
from allergy and reduce the risk of asthma. The other episode was Colin
Sanderson (head of Molecular Immunology) commenting that one of the
best people in the Institute was Steve Zubrick, the head of
Psychosocial Research -- given the usual contempt in which
psychologists are held by "serious" scientists, this was great
praise indeed! Bridges being developed between groups enhance the
chances of collaboration.
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Threats
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With all this success and delight that we have survived our birth, with
the new joint Commonwealth and State government $22.5 million
building program heading for an early 2000 completion date, with such
community support and government acceptance of our role, why am I
concerned for our future? Our vulnerability now relates mainly to
research funding and the support for our next generation -- our
current students and postdoctoral staff. We are finding that
research funding is much better in other countries and in other States
and that we cannot offer our senior and rising bright young minds
incentives to stay with us or even to stay in full time research. Some
are off to overseas positions or into the private sector or into
academic jobs with all the toil of teaching but at least some security.
Our most recent sadness was that Paul Burton and Jenny Kurinczuk have
been head-hunted back to the UK to tenured, well paid (at least double
the NHMRC salaries they are currently receiving) academic positions
at the University of Leicester. We will miss them greatly, but we can
take some pride in having provided an environment for these two
outstanding young people to develop their research careers to this
level.
Our policy of establishing an Institute by asking successful
scientists to join us and bring their own salaries (usually NHMRC
funded) was our only way of getting things going, but is not the way we
can continue. It ensured that we only had peer-reviewed science in the
Institute and meant that we could spend our precious and scarce
resources on infrastructure and not research salaries. This ensured
our survival, but it is not good policy in the longer term. The NHMRC
roulette is not conducive to recruiting the brightest and the best.
The Board needed little convincing to realise that such
vulnerability is unacceptable and we are now looking at ways of
securing our best people.
Independent institutes are disadvantaged compared with
universities because they do not receive direct infrastructure
support from the Department of Employment, Education and Youth
Affairs. Our Institute cannot match this year's increases in
academic salaries as the NHMRC decided not to fund such an increase for
research for its grant holders. Yet young scientists cannot be
expected to work for low wages when salaries in other similar
countries are much higher. We continue to lobby at Federal and State
level, and wonder why, with our successes in improving child health,
excellent research and scholarship, we are so undervalued in this
country.
Private funding alone is not the answer. I salute the likes of the
visionary Sir James Cruthers and all the past, current and future
corporate and private sponsors of research in Australia: what you
could now do for us is to become advocates to convince governments to
join with you in investing in our brightest and our best. Any less and
our capacity to do research and benefit from it will be limited.
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References
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- Holt PG, Yabuhara A, Prescott S, et al. Allergen recognition in the
origin of asthma. Ciba Found Symp 1997; 206: 35-49.
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Holt PG, Macaubas C. Development of long-term tolerance versus
sensitisation to environmental allergens during the perinatal
period. Curr Opin Immunol 1997; 9: 782-787.
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Stanley FJ, Croft ML, Gibbins J, Read AW. A population database for
maternal and child health research in Western Australia using record
linkage. Paed Perinat Epidem 1994; 8: 433-447.
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Stanley FJ, Watson L. Methodology of a cerebral palsy register. The
Western Australian experience. Neuroepidemiology 1985; 4:
146-160.
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Bower C, Stanley FJ. Dietary folate as a risk factor for neural-tube
defects: evidence from a case-control study in Western Australia.
Med J Aust 1989; 150: 613-619.
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Kees UR, Burton PR, Lu C, Baker DL. Homozygous deletion of the
p16/MTS1 gene in pediatric acute lymphoblastic leukemia is
associated with unfavorable clinical outcome. Blood 1997;
89: 4161-4166.
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Salvati PD, Ranford PR, Ford J, Kees UR. HOX11 expression in
pediatric acute lymphoblastic leukemia is associated with T-cell
phenotype. Oncogene 1995; 11: 1333-1338.
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Thomas WR, Smith W. House dust mite allergens. Allergy
1998; 53: 821-832.
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Thomas WR, Smith W, Hales BJ. House dust mite allergen
characterisation: implications for T-cell responses and
immunotherapy. Intern Arch Allergy Immunol 1998; 115: 9-14.
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Thomas WR, Flack FS, Callow MG, Chua KY. A high-molecular-weight
outer membrane protein that is a potential target for protective
immunity to type b and untypeable Haemophilus influenzae.
J Infect Dis 1992; 165 Suppl 1: S75-S76.
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Stumbles PA, Thomas JA, Pimm CL, et al. Resting respiratory tract
dendritic cells preferentially stimulate Th2 responses and require
obligatory cytokine signals for induction of Th1 immunity. J Exp
Med 1998. In press.
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McMenamin C, Pimm C, McKersey M, Holt PG. Regulation of IgE
responses to inhaled antigen in mice by antigen-specific gamma delta
T cells. Science 1994; 265(5180): 1869-1871.
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Author's details
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TVW Telethon Institute for Child Health Research, Perth, WA.
Fiona Stanley, AC, MD, FAFPHM, FRACP, Director, and Variety
Club Professor of Paediatrics, The University of Western Australia.
Reprints: Professor Fiona Stanley, TVW Telethon Institute for Child
Health Research, PO Box 855, West Perth, WA 6872.
Email: infoATichr.uwa.edu.au
URL:
http://www.ichr.uwa.edu.au
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