Early days: the Tasmanian Infant Health Survey and Sudden Infant Death Syndrome -
The post-SIDS era: taking stock -
New directions -
Genomics -
The future -
References -
Authors' details
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I ACCEPTED THE CHAIR IN COMMUNITY HEALTH at the University of Tasmania
in 1985 with the intention of setting up a research centre that focused
on epidemiological research into preventable causes of disease.
While I did not know how the centre would be funded, I was certain that
Tasmania would be a very competitive site for such research. Already,
valuable epidemiological studies on iodine deficiency, hydatid
disease and asthma had been conducted in the absence of significant
research infrastructure.1 The "Island State" provided
a perfect source population for unbiased selection of cases and
comparison samples or controls. Further, the land area and
population size (around 500 000 people) made follow-up of cohorts
relatively easy. Thus, Tasmania had important advantages for the two
major strategies used to search for environmental and lifestyle
causes of disease — case-control and cohort studies.
Funding from the Menzies Foundation came about through the input of
three people — Basil Hetzel, then Chief of the Commonwealth
Scientific and Industrial Research Organisation Division of Human
Nutrition in Adelaide, who had a close association with the Menzies
Foundation; Professor Ian Lewis, Dean of the Medical School at the
University of Tasmania and a member of the Menzies Foundation Board;
and Eric Wigglesworth, the Director of the Foundation. To determine
the likely success of such a centre, the Foundation Board held a
three-day workshop attended by representatives of State and Federal
health departments and the World Health Organization, notable
Australians in the field of public health, and distinguished British
epidemiologist Sir Richard Doll.
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History of the Menzies
Centre |
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1987 |
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Workshop ("Towards a Centre for Population
Health Research") in Hobart, Tasmania. |
1988 |
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Official opening in January. |
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Collection of Tasmanian Infant Health Survey
(TIHS) data began (prospective study on Sudden Infant Death Syndrome [SIDS]). |
1990 |
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Designated as a World Health Organisation
Collaborating Centre for the Prevention of Cardiovascular Diseases. |
1991 |
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Provides prospective evidence confirming
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importance of prone sleeping position as a
cause of SIDS (Lancet 1991; 337: 1244-1247). |
1992 |
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Evidence that SIDS death rate was falling
after a national campaign on infant sleeping position. |
1993 |
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Research helps explain how prone position
interacts with other factors to increase risk (N Engl J Med 1993; 329: 377-382). |
1995 |
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First follow-up of TIHS cohort searching for
early life influences on childhood diseases. |
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Shows that the major decline in SIDS deaths
from 1991 onwards is the result of changes in infant sleeping position (JAMA
1995; 273: 783-789) |
1997 |
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Contract signed with AMRAD pharmaceutical
company. Provides funding for Genetic Epidemiology Unit. |
1997-2000 |
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Follow-up of the Tasmanian Infant Health Survey
cohort into childhood provides important evidence about early life determinants
of risk for osteoporosis, blood pressure and asthma (J Clin Endocrinol Metab
1998; 83: 4274-4279; J Bone Miner Res 1999; 14: 146-151; BMJ 1999; 319:
1325-1329; Thorax 1999; 54: 664-669). |
2000 |
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Named "Tasmanian Icon" by State Premier. Core
funding doubles. |
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Key events
Major scientific achievements.
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Subsequently, the Menzies Foundation Board decided to support the
establishment of an epidemiology research centre, to be named the
Menzies Centre for Population Health Research. The Foundation then
met with the Tasmanian Premier and Minister for Health, who matched
the Foundation's initial contribution of $100 000 per year.
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Before my departure from Sydney University, I had been reviewing the
data on disease distribution in Tasmania. Sudden Infant Death
Syndrome (SIDS), with an annual rate in Tasmania twice the national
average, stood out. The head of neonatology at the Royal Hobart
Hospital, Neville Newman, convinced me that this should be the
subject of a major research effort. The cause had not been clearly
identified, and epidemiological research had been limited. With
helpful input from Geoffrey Berry, Professor of Biostatistics at
Sydney University, we planned the first prospective cohort study on
this condition. Preliminary work began just before the decision of
the Menzies Foundation to support the establishment of the Centre.
The epidemiology research group within the Medical School at the
University of Tasmania consisted of one epidemiologist, the
research fellow Trevor Beard, and limited support staff. Even with
the extra $200 000 that the establishment of the new Centre brought, it
would not have been realistic to work on a broad front. It was decided
that we would focus most of our effort on the new SIDS research program.
The next step was to build an appropriately skilled team. We
advertised for another epidemiologist and a biostatistician, but it
proved very difficult to attract qualified applicants. It seemed
that Australian academics were either not interested in living in
Tasmania, or were not confident their careers would flourish there.
This problem was compensated for by a stroke of good luck when a young
Tasmanian medical graduate, Anne-Louise Ponsonby, became our first
postgraduate student, working on SIDS. She put an incredible amount
of intelligently directed energy into the SIDS program, and
together, with financial help from the Australian Rotary Health
Research Fund, we were able to develop momentum in the project. In
1988, we initiated the first full data collection for the cohort study
— a huge endeavour that involved measurements each year in 1500
infants and their mothers on three occasions in the first three months
after birth.
That we could get this work under way was pleasing, but we needed to find
well-qualified biostatisticians. Given the previous lack of
success with advertising in Australia, I decided to use our
international network. Sir Richard Doll referred Michael Jones, a
young Master of Science graduate from Oxford, who was recruited to our
ranks, and then Laura Gibbons, from the University of Massachusetts,
joined us. This relatively small and young team of investigators
coordinated the conduct, data management and analysis of the SIDS
program. They also assisted with less well resourced but developing
areas in cancer and cardiovascular disease.
In late 1990 evidence was accumulating from case-control studies
that prone sleeping position might be a major cause of SIDS, but the
research was retrospective, creating concerns that recall bias
might explain the findings. We had the only prospective data in the
world and were able to show that the association was equally strong
prospectively, ruling out recall bias.2 A number of countries,
including Australia, launched campaigns to encourage parents not to
place babies on their stomachs in the cot, with astonishing results —
the death rate from SIDS in Australia fell from 507 in 1990 to 139 in
1998, with similar falls in a number of other countries.3
While our work was not the only important contribution to the
understanding of this major cause of SIDS, it provided an important
piece of evidence needed for solving the puzzle. Later, in 1993, our
team explained why prone sleeping position seemed to exert a
different effect in winter than summer and a different effect across
countries.4 Then, in 1995, we provided
evidence that showed clearly that the fall in deaths could only be
attributed to the changes in prevalence of prone sleeping
position.5
This success will undoubtedly rank as one of the major contributions
of the Centre in the years to come. It also established the
organisation as one which, in its special location, could have a
significant impact on international medical science. It was the
much-needed platform that would underpin future recognition and
opportunities.
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The death rate from SIDS fell so rapidly after the prone sleeping
position campaign that, by late 1991, it was clear there would
eventually be insufficient cases occurring annually in Tasmania for
epidemiological research (when we started the SIDS program, there
had been an average of 27 cases a year for an extended period, and by 1998
there were only three). While this outcome was tremendously
gratifying, it was clear that the research money to support our staff
of now approximately 20 would dry up unless we repositioned our
research program. This was confirmed by the National Health and
Medical Research Council (NHMRC) Regional Grants Interview
Committee's decision not to recommend refunding of our cohort study
for 1992. We went from triumph to a period of considerable adversity.
One of our first responses was to tell the Tasmanian public that we
needed its financial and moral support. They responded generously.
With a major public fundraising appeal, helped greatly by our Board
and new Chairman John Tomlinson, and a timely decision by the United
States National Institutes of Health, we were able to continue the
study long enough to thoroughly evaluate the impact of the prone
sleeping intervention campaign.
In 1992, I took some time to review where we were going as an
organisation and to think about where our future research
opportunities might lie. I visited people like Richard Doll in
Oxford, who had provided very helpful mentoring since 1987. I also had
discussions with Ken Rothman (author of Modern
epidemiology6), and Dimitris
Trichopoulos at Harvard. These visits confirmed that, if we were to
continue to conduct work of global significance, we would have to
search even more thoroughly for gaps in knowledge that might be filled
by an epidemiological approach. I was also convinced that we would
need to develop stronger working relationships with basic
scientists if we wished to use epidemiology to understand aetiology.
These strategies were challenging, but all our team had learned a
great deal from the SIDS research experience.
While overseas, I also upgraded my skills in organisation and
management by attending a management course in Salzburg, led by Peter
Drucker, one of the world's most prominent management theorists.
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The perspectives gained during my overseas visit were incorporated
into planning from 1992 onwards. The major new strategy we decided on
was to follow the Tasmanian Infant Health Survey (TIHS) cohort, now
numbering 11 000 infants and children. The focus would be to search for
links between early life exposures and later disease, using our
extensive database of infant measurements that provided
information on more than 450 variables measured during the first
three months of life. One disease we looked at was asthma, an important
disease for which preventable causes had not yet been identified and
for which there was a shortage of good epidemiological data. This
investigation would be coordinated by Anne-Louise Ponsonby, with
help from David Couper, a biostatistician who had joined us from
Seattle. We also increased our activity in research on the
development in childhood of risk factors for cardiovascular disease
and diabetes.
Fitting into this theme was the new program started by a recent recruit
from the Garvan Institute in Sydney, Graeme Jones (we were finally
starting to see interest in work opportunities from well-qualified
Australians outside Tasmania). He had a strong track record in
osteoporosis in the elderly, and he used that background to focus on
the impact of early-life factors on bone density in childhood.
Fortuitously, interest in the "Barker hypothesis", which concerns
the impact of fetal development on later disease, was gaining
momentum. We were well placed to make an important contribution in
this field, and our capacity was greatly enhanced by the addition of
Ruth Morley, from the Institute of Child Health in London.
Supplemented by smaller research efforts in cancer and adult
cardiovascular disease, by 1994 we were able to see evidence that the
research program was growing again. Between 1994 and 2000, the team
was able to attract 17 new NHMRC grants from 38 applications
submitted. This overall level of success was built on the tremendous
preparedness of the Tasmanian public to be involved in the research.
Response rates for case-control studies in this period were about 90%
for cases and 80% for controls sampled from the electoral rolls, with
comparable figures for cohort follow-up.
In addition to our growing research effort we took on an important role
in ensuring that knowledge was transferred to countries with less
developed research capacity. The World Health Organization
designated our institution as a Collaborating Centre for the
Prevention of Cardiovascular Disease (CVD) a decade ago. That role
has expanded steadily to the point where the Centre is assisting in
studies on CVD in countries including Vietnam, Fiji and Samoa, where
CVD and diabetes are producing an unexpectedly high disease burden.
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For the first seven years (1988-1995) the Centre focused solely on the
environmental and lifestyle causes of disease. Meanwhile, others
had been using the deep family pedigrees available in Tasmania to
search for genetic causes of diseases following a Mendelian pattern
of inheritance. Novel genes or linkages were discovered for several
conditions, including multiple endocrine neoplasia and
Huntington's disease.
These successes were based on special features of Tasmania that are
replicated in few other locations, namely (i) a population descended
largely from identifiable founder families; (ii) comprehensive
genealogical records; (iii) a modern healthcare system capable of
identifying disease outcomes; (iv) a demonstrated capacity to
involve the population in studies; and (v) organisational
structures to facilitate the research.
In 1995, David Mackey, a Tasmanian medical graduate and
ophthalmologist at the Victorian Eye and Ear Hospital, approached
us. He was undertaking important work in Tasmania on the more complex
genetics of glaucoma. He wanted a base in Tasmania, and the Walter and
Eliza Hall Institute, in Melbourne, was seeking a Tasmanian
institution to manage new research and development syndicate funds
to support his research. We accepted the role and our interest in the
use of epidemiology to find genes for human diseases increased. Then,
in 1996, the Australian pharmaceutical company AMRAD approached us
about increasing its involvement in gene discovery in Tasmania
through the Menzies Centre. We agreed, on the condition that the
funding would be for a genetic unit that would employ people who could
provide intellectual input to the work from a Tasmanian base. AMRAD
signed a contract in 1997 for a five-year grant of $2.5 million, and, in
1998, we attracted Tasmanian molecular geneticist Michele Sale to
coordinate the work. With financial and other help we were able to very
quickly get projects under way in multiple sclerosis and
osteoarthritis, and have continued to develop activity with
Cerylid, a spin-off from AMRAD formed to operate its discovery arm.
The genomics development has also led to an increase in postgraduate
student training at the Centre, with five PhD students currently
enrolled.
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During the past 12 months there have been several important
developments for the Centre, driven by our very committed Board,
chaired by Jean Trethewey, and strongly supported by the Dean of the
Faculty of Health Science at the University of Tasmania, Allan
Carmichael. The Tasmanian Government introduced an "Icons
Program", which supports the Tasmanian Symphony Orchestra and our
State cricket team. To this list Premier Jim Bacon added the Menzies
Centre, with a commitment to provide $500 000 a year to help our
organisation develop its capabilities. This, together with a large
donation in 2000 from the United States-based Atlantic
Philanthropies Inc, has placed us in a previously unimagined
position to recruit more staff and drive our research program.
To enable us to undertake these future developments with vigour, the
University of Tasmania Council has established the Menzies Centre as
an independent company limited by guarantee, remaining within the
university structure. In 2002, the Centre will become the "Menzies
Research Institute". Already, the Centre has grown to support a staff
of 60. The new institute is likely to start 2002 with a budget of
approximately $5 000 000 that will see staff numbers increase to more
than 100, working on both environmental and genetic causes of
disease.
A major NHMRC grant of $2 290 000 over the next five years will enable us
to study a cohort of Australians first measured as schoolchildren in
1985. They will be followed up for the emergence of adult disease, and
it is anticipated this will provide the first direct evidence
available on the impact of childhood lifestyle and biology on
diseases such as coronary heart disease. A collaboration with
similar cohorts in the US and Finland has already been established. A
new director of the Cohort Studies Unit, Alison Venn, who has a strong
background in this research strategy, has been recruited from the
Centre for the Study of Mothers' and Children's Health at La Trobe
University to coordinate developments. A large adult cohort study in
Tasmania, with a focus on exposures that occur closer to the time of
disease development, will also commence in 2002. Both studies will
benefit from the input of a now-strong biostatistics group of three
staff headed by one of our own PhD graduates, Leigh Blizzard.
The level of genetic research activity will expand greatly. Tasmania
presents opportunities as good as any in the world for gene discovery,
and we intend to take up these opportunities. An increasing number of
epidemiological studies at the Centre are focused on finding novel
genes or validating candidate genes identified through animal or
cell studies, or bioinformatic "data mining". This growth in
activity reflects the recognition by commercial and government
sources of the opportunities here, as well as the developing capacity
of our genetic unit.
Increasingly, our "environmental" epidemiologists and
biostatisticians are developing their interests and skills in
genetic research. This has not only led to the more rapid development
of a critical mass for projects on gene discovery and validation, but
has also opened up the possibility for in-depth investigation of
gene-environment interaction. Projects with this focus are already
under way in multiple sclerosis. There is great scope for us to
contribute in an internationally significant way to the
understanding of gene-environment interactions using Tasmania's
unique population and our skill base.
In the coming decade Australia will be relying more and more on its
medical research institutes to maintain its competitive advantage
in a knowledge-based global economy. We are confident that the new
Menzies Research Institute will be making its contribution.
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- King H, editor. Epidemiology in Tasmania. Canberra: Brolga Press,
1987.
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Dwyer T, Ponsonby AL, Newman NM, Gibbons LE. Prospective cohort
study of prone sleeping position and sudden infant death syndrome.
Lancet 1991; 337: 1244-1247.
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Australian Bureau of Statistics. Deaths, Australia, 1990, 1998.
Canberra: ABS, 1998. (Catalogue no. 3302.0/3303.0.)
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Ponsonby AL, Dwyer T, Gibbons LE, et al. Factors potentiating the
risk of SIDS associated with the prone position. N Engl J
Medicine 1993; 329: 377-382.
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Dwyer T, Ponsonby AL, Blizzard CL, et al. The contribution of
changes in the prevalence of prone sleeping position to the decline in
SIDS in Tasmania. JAMA 1995; 273: 783-789.
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Rothman K. Modern epidemiology. Boston: Little John and Co., 1986.
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Menzies Centre for Population Health Research
Terence Dwyer, MD, FAFPHM, Director.
Reprints will not be available from the author. Correspondence:
Professor T Dwyer, Menzies Centre for Population Health Research, 17
Liverpool Street, Hobart, 7000 TAS. t.dwyerATutas.edu.au
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