PathWay Autumn 2008 - Issue #15
Genetics:
GENETICS:
redefining diagnosis, disease
and drug therapy
PHARMACOGENETICS:
TAILOR-MADE TREATMENTS
A REVOLUTIONARY DISCOVERY
PCR TESTING:
HAEMOCHROMATOSIS:
IGNORANCE IS NOT BLISS
REDEFINING DIAGNOSIS, DISEASE AND DRUG THERAPY ALTERNATIVE’ | PHARMACOGENETICS: TAILOR-MADE TREATMENTS | PCR TESTING: A REVOLUTIONARY DISCOVERY | HAEMOCHROMATOSIS: IGNORANCE NOT BLISS
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20/2/08
PathWay #15 - Cover
Autumn 2008 | Issue #15
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PathWay #15 - Text
21/2/08
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Page 1
ADVISORY BOARD
Contents
Dr Debra Graves (Chairman)
Chief Executive, RCPA
Dr Tamsin Waterhouse
Deputy CEO, RCPA
Dr Edwina Duhig
Director of Anatomical Pathology QHPS
(Prince Charles Hospital)
Dr Andrew Laycock
Chairman Trainees Advisory Committee, RCPA
PATHWAY
Autumn 2008
Issue #15
Dr David Roche
New Zealand Representative, RCPA
Wayne Tregaskis
S2i Communications
PUBLISHER
Wayne Tregaskis
EXECUTIVE EDITOR
Dr Debra Graves
COVER STORY
EDITOR
Dr Linda Calabresi
A perfect fit: Pharmacogentetics
ART DIRECTOR
Jodi Webster
8
Advances in genetics are making it possible to tailor treatments
to the individual patient.
FEATURES
ADVERTISING SALES DIRECTOR
Sue Butterworth
Disciplines in depth: Back to basics
PUBLISHING CO-ORDINATOR
Andrea Plawutsky
Pathology’s newest subspecialty, genetics looks set to change the
future of medicine’s approach to disease and treatment.
PathWay is published quarterly for the Royal College
In profile: Family matters
of Pathologists of Australasia (ABN 52 000 173 231)
by S2i Communications, Level 9,
16 Spring St Sydney 2000
12
16
Dr Graeme Suthers’ drive and vision have had a major influence
on Australia’s familial cancer services.
Tel (02) 9251 8222 Fax (02) 9247 6544
Testing testing: The ABC of PCR
PrintPOST approved PP60630100114
20
Bianca Nogrady reports on how PCR testing has changed the face
of medical diagnosis.
Spotlight on disease: Metal detectors
26
Haemochromatosis: easy to diagnose and treat but still often
going undetected until too late.
The Royal College of Pathologists of Australasia
Tel: (02) 8356 5858
Email: rcpa@rcpa.edu.au
S2i Communications Pty Ltd
Tel: (02) 9251 8222
Cutting edge: High expectations
32
Prenatal genetic screening is becoming commonplace in
Australia. Dr Kathy Kramer looks at its benefits, limitations and
potential.
Email: wayne@s2i.com.au
PathWay
Email: pathway@rcpa.edu.au
http://pathway.rcpa.edu.au
Foreign correspondence: Wisdom in the Solomons
35
Australian expertise is behind the setting up of the Solomon
Islands’ first anatomical pathology laboratory.
FOR FURTHER INFORMATION ON THE ROYAL COLLEGE OF
PATHOLOGISTS OF AUSTRALASIA OR ANY OF THE FEATURES
IN THIS ISSUE OF PATHWAY CHECK OUT THE WEBSITE
www.rcpa.edu.au
PATHWAY_1
Key Incident Monitoring and Management
Systems (KIMMS)
Pathology in Australia has been a
leader in accreditation and quality
assurance. Recent studies in many
countries have shown that the majority
of adverse patient incidents occur in the
non-analytical phase of the test-requestreport cycle.
To minimise the risk of errors and
incidents in pathology, the pre- and
post- analytical phase of testing need to
be measured and monitored. KIMMS is
designed to provide pathology practices
with the tools for continuous
measurement and monitoring of key
incident indicators.
KIMMS provides the means by which
laboratories can be encouraged to
monitor rate of adverse incidents
affecting patient safety and welfare;
through benchmarking against peers
and state-of-the-art, a mechanism is
provided for the systematic risk
management and improvement of
performance in agreed key areas.
KIMMS Objectives:
x To establish a national data set
for pathology incidents
x To develop the data set to enable
participants to measure and monitor
pathology incidents
x Utilise the data to set achievable
national benchmarks for good pathology practice in the pre- and postanalytical phase of testing
x Work with participants, by exchanging information, to educate
laboratories on methods to reduce
errors
x Raise awareness of safe work
practices which in turn will reduce
errors and increase patient safety
x Set standards for best practice in
the pre– and post-analytical areas of
laboratory work
KIMMS offers pathology laboratories:
x Data and graphical analysis, showing trend analysis
x Benchmarking against peers
x Educational content
For further information contact:
Penny Petinos
KIMMS Coordinator
pennyp@rcpa.edu.au
Ph: +612 8356 5814
REGULARS
From the CEO
Welcome from RCPA CEO Dr Debra
Graves
4
Under the microscope
6
News + views
6minutes news
Interesting news from around the
world
30
Finance finesse
38
Financial advisor, Greg Lomax gives
some timely tips on superannuation
investments.
Conference calendar
42
Postscript
64
Fairy tales and feral carbon: Dr Pam
Rachootin proposes pathologists are
ideally placed to save the planet
WISDOM IN THE
SOLOMONS
PAGE 35
IMAGES OF IRAN
PAGE 46
LIFESTYLE
Travel: O Paradiso
Pangkor Laut Resort in Malaysia is a heady combination of beauty,
serenity and luxury.
44
Travel: Images of Iran
Judy Myers finds a country rich in history, culture, colour and
hospitality
46
Travel doc
On the trail of the tiger: Dr Harsha Sheorey has the experience of a
lifetime while on safari in Central India
49
Private passions
Doing the hard yards: Mike Ralston’s hankering for hiking has certainly
seen him cover some ground.
52
Recipe for success
Expelled to greatness: Carolyn Alexander meets lauded chef, Andrew
McConnell, the talent behind Melbourne’s Three, One, Two.
54
Dining out
Food with a view: Combining a spectacular view with fabulous food
makes for a truly memorable dining experience
57
The good grape
Chic sherries: Ben Canaider explains why sherry is enjoying a
renaissance around the world
61
Rearview
62
Racing to unravel the mystery of AIDS: Who discovered AIDS? Dr
George Biro looks at one of the great feuds of our time
PATHWAY_3
from the CEO
Welcome
to the 15th Edition of PathWay
revolution started in medicine in 1953
when Watson and Crick discovered
DNA.
A
Over the ensuing 55 years many
advances have occurred in the field of
Genetics which have had profound effects
on our understanding of disease and our
response to it.
This edition of PathWay focuses on the
“Genetic Revolution” examining specific
areas where genetic testing impacts on
healthcare and the challenges that lay
ahead for countries dealing with this
phenomenon.
For many people genetic testing is a
brave new world and perhaps even a little
abstract, with concepts such as “predictive
testing” and its far reaching consequences.
But the reality is genetic testing is here and
already contributing significantly to the
advancement of medicine.
As a result, it is time for politicians,
health care administrators and the general
and medical communities to be better
informed about genetics and what we need
to do to ensure the healthcare system is
well-equipped to deal with this revolution.
Perhaps the most widely known form of
genetic testing is that involved with prenatal
screening, looking for conditions such as
Down syndrome.
This type of testing and the issues
surrounding it are explored in the article by
Dr Kathy Kramer, “High Expectations”.
While a very important area it must be
stressed that this is only one application of
genetic testing, and only the tip of a very
large iceberg.
Other major areas of genetic testing that
will be explored include predictive testing in
adults for susceptibility to disease and
responsiveness to drug therapy, the genetics
of cancers and genetics of organisms
causing infectious diseases.
4_PATHWAY
In our article “The ABC of PCR”, the
use of Polymerase Chain Reaction (PCR) to
detect the genetic make up of organisms is
outlined. Developed in the early '90s, the
technique of PCR testing allows scientists
to produce or amplify genetic material to a
sufficient “volume” to enable the detection
of particular base pair sequences in genes
that code for particular conditions or
organisms.
The other very exciting area of genetics
that we look at is that of predicting a
person’s responsiveness to a particular
medication. This is explored in the article “A
perfect fit: Pharmacogenetics”.
Already there are a number of genetic
tests that are being used to determine a
patient's suitability for particular treatments.
And the number of new tests becoming
available over the next few years is likely to
In the article “Family Matters”, we
profile Dr Graeme Suthers who is the head
of the South Australian Familial Cancer
Service, which is doing remarkable work in
this important area of genetic testing.
increase dramatically. This will have
Dr Graeme Suthers, a genetic
pathologist and Chair of the College's
Genetics Advisory Committee is one of a
number of pathologists driving the
College's push for a National Framework in
Genetics in Australia.
offered a drug if it is known they will be
As is so often the case with new
technologies, the funding, workforce planning,
regulatory, ethical and quality/standards need
to be planned in a systematic way to ensure a
high quality appropriate service is delivered.
Compared to the UK, many countries
including Australia are slow in addressing
these issues. In the UK, over 300 genetic
tests are funded by the NHS, in Australia the
Medical Benefits Schedule includes only ten,
with some States funding some genetic
tests in a somewhat ad hoc manner.
The College thinks it is time for urgent
action to be taken to keep Australia at the
forefront of the medical world.
In the feature “Metal Detectors”, we
examine another area of genetic testing for
the condition known as haemochromatosis.
We talk with Professor David Ravine about
this very important genetic test and explore
the question of population screening for the
disease.
tremendous benefits for patients as they will
receive much more targeted treatments, and
also has the potential to save considerable
amounts of money with people only being
responsive to it.
In the pharmacogenetics article,
another major area of genetic testing - the
testing of the genetic make up of cancers
themselves - is discussed. Variations in the
genetic profile of cancer cells compared to
normal cells is a key area of research and
indeed in a number of areas is already used
in routine diagnostic practice. Greater
understanding of these differences offers
benefits in diagnosis, prognosis and
treatment of cancer.
By understanding the exact type of
tumour present more targeted therapy can
be provided, the classic example being the
effectiveness of trastuzumab (Herceptin) in
HER2 positive breast cancer.
We hope you enjoy this exciting very
important edition of PathWay.
Dr Debra Graves
CEO, RCPA
Symbion Pathology is fast becoming one of
Australia’s leading private pathology groups,
performing more than 10 million patient
episodes each year.
With a national network of distinguished
pathology providers positioned throughout
Victoria, New South Wales, Queensland,
Western Australia and the Northern Territory,
our highly experienced pathologists and
medical scientists have access to state-ofthe-art technology and automated workflow
systems to enable high throughput and fast
turnaround of analyses and reports.
At Symbion Pathology we remain at the
forefront of delivering innovative and
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are committed to delivering a service based
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Our National Network of
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Symbion Health Ltd ABN 56 004 073 410
under the microscope: news + views
Australia Day honours
hree Australian pathologists were
among those recognised on this year’s
Australia Day honours list.
T
Boost for
Hep C/HIV
research
Dr Colin Laverty (pictured right) was
awarded a Medal of the Order of Australia
(OAM) for his service to medicine,
particularly gynaecological cytology and
histopathology.
He established the role of human
papillomavirus in cervical cancer and has
helped advance cervical screening
services in Australia. The award also
acknowledged Dr Laverty’s contribution to
art, particularly Indigenous art, both in
Australia and overseas.
Immunologist, Professor Paul Gatenby,
foundation dean of ANU medical school
was made a Member of the Order of
Australia (AM) for service to medicine in
the field of clinical immunology as a
clinician and researcher, to the
advancement of medical education, and
through professional organisations.
epatitis C and HIV research has
H
been given a significant boost
with the announcement of $17.7
million in funding being awarded to
the University of NSW by the
Former chief executive officer of the
WA Centre for Pathology and Medical
Research, Dr Keith Shilkin was also made
a Member of the Order of Australia (AM)
for his work in developing WA’s public
sector pathology services. His
contributions to professional organisations
as well as to the Jewish community were
also recognised.
National Health and Medical
Research Council (NHMRC) to
advance understanding of the two
diseases.
The grant, the largest in
Australia’s history, was announced
last month by the Minister for Health
and Ageing, Nicola Roxon.
Professor David Cooper from the
National Centre in HIV Epidemiology
More anatomy for Sydney
Uni med students
and Clinical Research (NCHECR) will
lead a nine person team from across
Australia, combining researchers in
virology and immunology with those
who have expertise in translating
fter a year-long review of its curriculum,
findings in the laboratory into human
Sydney University has more than
clinical trials.
A
doubled the teaching time devoted to
anatomy as part of its graduate medical
course. The four year course will now
include reportedly 1200 hours of anatomy
study, significantly more than the 500 hours
allocated in the previous curriculum.
Part of the grant has been
allocated to fund a five year project
to develop new strategies to prevent
and treat hepatitis C, which is
currently affecting more than
260,000 Australians.
The move is believed to be in in
response to complaints from many in the
Leading the project, University of
medical community, including the students
Adelaide virologists Dr Michael
themselves, that graduates of the course
Beard and Dr Karla Helbig, along
were inadequately trained in a number of
with colleagues from the University
the basic medical sciences, including
of NSW, hope to identify antiviral
anatomy. It is believed that the revised
proteins that can work effectively
curriculum, the first revision in 11 years also
against the hepatitis C virus with the
contains increases in the teaching time
aim of developing vaccines and
allocated for other sciences such as
treatments for the disease.
pathology.
6_PATHWAY
Australian innovation
advances genetic
technology
A new type of RNA microarray chip developed by Australian scientists has been
licensed to one of the world’s largest life sciences technology companies, Invitrogen.
Dr Marcel Dinger and Professor John Mattick from the University of Queensland’s
Institute of Molecular Bioscience designed the proprietary technology that will help
analyse which genes are being expressed at any one time in a particular cell.
Each cell in the body contains a full set of genes, however different cells express
different subsets of these genes. Previously it was believed these genes only coded
mainly for proteins via the production of ‘messenger RNAs’. However it has been
discovered that many other genes produce non-coding RNAs, the functions of which
are yet to be determined.
The newly licensed RNA microarray chip can uniquely identify tens of thousands of
coding and non-coding RNA sequences. For the first time, one product can identify
large numbers of both types of RNAs and the new technology has the potential to
make a significant impact in the areas of cancer and stem cell research where RNAs
have been implicated.
The technology has been licensed through IMBcom, University of Queensland’s
company for the commercialisation of intellectual property arising from research
conducted at the Institute of Molecular Bioscience.
GPs ordering
more path
tests
ustralian GPs are ordering significantly
more tests and investigations,
particularly pathology tests than they were
six years ago, new data show.
A
Findings from a report released by the
Australian Institute of Health and Welfare
show GPs ordered 44% more tests (or
batteries of tests) per 100 patients in
2006-07 compared with 2000-01.
Researchers suggest incentives for
improved care of people with chronic
diseases such as diabetes may, at least
partly be responsible for the increase.
The report, General Practice Activity
in Australia 2006-07, reports the results
from the ‘Bettering the Evaluation and
Care of Health’ (BEACH) program’s
national survey of 100,000 GP-patient
encounters.
PATHWAY_7
cover story
A perfect fit
Pharmacogenetics
GENETICS CAN PREDICT A PERSON’S RESPONSE TO A DRUG EVEN BEFORE THEY’VE
TAKEN IT. PETER LAVELLE LOOKS INTO THIS BRAVE NEW WORLD.
8_PATHWAY
t was a lot better to be born at the end of
last century than at the beginning. In
1900, life expectancy wasn’t much over 30
years of age. But we ended the 1900s with
a life expectancy of 77 years for men and
83 for women.
I
Better sanitation, hygiene and nutrition
played a big part. But it was the
emergence of the pharmaceutical industry
that gave us vaccines, antibiotics,
anaesthetics and host of other drugs, that
helped bring the killer diseases of centuries
past under control.
So we’ve a lot to be grateful for.
Still, drug treatment is a clumsy
business. It's mostly trial and error; a
doctor prescribes a certain drug, hoping it
will work, and if it doesn’t, tries another.
There’s not much certainty - one person
responds well to a drug while another is
resistant to it, or develops side effects so
the drug has to be stopped.
Why?
We’ve known since the 1950s that
people react differently to different drugs;
and that a person's age, sex, weight, and
ethnic background all influence how he or
she will react.
But what’s becoming clearer in the
beginning of the 21st century is how
important an individual's genetic makeup is
in determining a person’s reaction to a
particular drug.
Thanks to an emerging discipline called
‘pharmacogenetics’, clinicians are
increasingly using genetic testing to
identity who is suitable for a particular
treatment - enabling clinicians to tailor drug
treatments to particular individuals.
It's not a new concept - the term
pharmacogenetics was coined in 1958 but what is new are the advances in our
understanding of the human genome and
the technologies we now have to detect
abnormalities in individual genetic profiles.
Professor Ross McKinnon is Professor
of Pharmaceutical Biotechnology in the
School of Pharmacy and Medical Sciences
University of South Australia. “A drug is a
molecule that goes through a journey in
someone’s body, and that journey depends
on interactions with different proteins,” he
says. “Those proteins are encoded by
genes, and those genes vary from person
to person and so the journey differs in each
person. In most cases the differences
won’t mean much but in others these
differences can have a dramatic impact.”
The genetic differences themselves
seem minor on the face of it.
In most cases they are just mutations
in single bases of DNA known as single
nucleotide polymorphisms (SNPs) variations that occur when a single
nucleotide (A, T, C or G) in the genome
sequence is altered.
In some individuals, there may be
multiple different single base mutations, or
multiple copies of the same mutated
sequence.
Some people may have inherited the
mutations from one parent (this is called
heterozygous) or from both parents
(homozygous).
Fortunately, many of these mutations
can be tested for and identified, thanks to
advances in genomics and in genetic
testing.
There are two ways of testing for
genetic mutations affecting drug
metabolism, says Professor McKinnon.
One involves looking for the faulty
genes themselves; that is to do genotypic
tests to look for the abnormal DNA bases
(single nucleotide polymorphisms or SNPs)
using polymerase chain reaction (PCR)
techniques. These tests can be done on
blood samples or cheek swabs.
The other approach is to look for the
consequences of the abnormality, by doing
assays of the enzyme(s) that break the
drug down in the body, or of the
metabolites of the drug - these are blood
tests.
Professor Ross Pinkerton is a
paediatric oncologist at Royal Children's
Hospital, Brisbane.
>
But the consequences can be
dramatic, says Professor McKinnon.
Genes that code for proteins that
affect the way a drug is metabolised may
be altered so they work differently or they
don’t work at all.
If, for example, the mutation produces
enzymes that are less effective in breaking
down a drug into its metabolites, the
person will have abnormally high levels of
that drug in the body, causing toxicity and
side effects.
If the mutation produces more of the
enzyme than normal, this may lead to
faster metabolism of the drug, and the
drug is less effective than in the normal
population.
Where there are several copies of the
same abnormal gene, or the person is
homozygous for the altered gene, then the
effect can be especially dramatic.
PATHWAY_9
Identifying the
enemy
n the world of tailored medicine there are two sides to the equation.
Isolating variations in a person’s genetic profile to see whether a treatment
will be effective is an important component of customising therapies.
I
However, on the flipside it is often equally important to know the genetic
make up of the disease that is to be treated.
One area of medicine where this is particularly true is cancer.
The ‘genetic revolution’ has enabled a greater understanding of a whole
range of cancers.
In lymphoma for example, advances in genetics have led to greatly
improved diagnostic accuracy, says Clinical Professor Dominic Spagnolo from
the University of Western Australia.
“Being able to identify antigen receptor genes in B and T lymphocytes
has allowed us to be more definite in difficult-to-diagnose cases of
lymphoma,” he says.
Advances in this discipline have also led to the identification and
assessment of genes that control cell growth, differentiation and death.
“In lymphoma the inappropriate switching on or off of these genes
correlates with the progression of the disease and indicates how aggressive
the cancer is likely to be,” says Professor Spagnolo who is also consultant
pathologist at PathWest Laboratory Medicine, Perth.
The presence of such genetic markers therefore has become predictive of
patient outcomes and hopefully will enable the tailoring of future lymphoma
therapies, he adds.
In other cancers the use of genetics to determine suitability of particular
treatments is already well advanced.
Breast cancer is a classic example says Dr Adrienne Morey, senior staff
specialist in anatomical pathology at St Vincent’s Hospital, Sydney.
“It is becoming increasingly apparent that breast cancer is not a single
disease but a group of diseases with different molecular profiles that are
linked to specific genetic defects.”
“New therapies are being developed which target different subgroups of
the disease, the most widely known probably being trastuzumab (Herceptin)
and lapatinib (Tykerb) which are indicated only in cancers that have an overexpression of the HER-2 protein to which the drug binds,” she says.
Only one fifth of all breast cancers have this over-expression. Genetic
testing to identify this subgroup ensures these new (expensive) treatments are
only given in cases where they will be most effective, Dr Morey says.
As the genetic profiles of more and more cancers are identified, advances
in diagnosis, prognosis and effective therapies look set to follow.
In addition to breast cancer and lymphoma, cancers of the colon, prostate
and ovary are just some of the many malignancies that are currently the
subject of genetic research.
Dr Morey predicts that down the track, more targeted therapies will be
developed and pathologists will be increasingly asked to identify the genetic
profile of individual cancers as such knowledge becomes a fundamental
component of determining treatment.
10_PATHWAY
One of the drugs he uses to treat
children with acute lymphoid leukaemia
(ALL) is 6-mercaptopurine, a thiopurine
drug that is usually well tolerated and
used as a maintenance drug.
Normally 6-mercaptopurine is broken
down in the body by thiopurine
methyltransferase (TMT). But some
children don’t have this enzyme.
“In these children [6-mercaptopurine]
is toxic. They get severe neutropaenia,
that is they get dangerously low white cell
counts that leave them susceptible to
infection.”
Other children have greater than
normal levels of TMT and in these
children, the drug doesn’t have the
therapeutic effect it normally should.
The faulty gene can be detected using
genotypic testing, or by testing for the
levels of metabolites of 6-mercaptopurine.
“Those kids without the enzyme have
low levels of metabolites, while those with
higher than normal levels of the enzyme
have high levels of the metabolites,” he
says.
These tests aren’t routinely done on
children commencing treatment with
6-mercaptopurine, but they will be done if
a child shows neutropaenia or isn’t
responding to treatment. If the test shows
a faulty gene and/or abnormal levels of
metabolites, the dosage of
6-mercaptopurine is adjusted.
Many of the advances in
pharmacogenetics have been in oncology
(diagnosis and treatment of cancers),
largely because of the important role
genetics plays in the genesis and
inheritance of cancers.
But it is by no means confined to
oncology.
It is now being used in the prevention
of blood clots, in inflammatory bowel
disease management, in the treatment of
high blood pressure and in viral illnesses.
Genetic testing is already being widely
used in the treatment of hepatitis and HIV,
where the genotype of the virus is being
used to predict the response to drugs,
says Professor McKinnon.
Some people have an exaggerated
response to the anti-clotting agent,
warfarin. They may not metabolise it or
they may have a gene that increases
“We are still unravelling the
genetic differences that
underlie the variation in
response from person to
person. So there are plenty
of challenges”
warfarin's effects on the clotting cascade.
These people are at risk of catastrophic
bleeding. Both types of mutations can be
identified with gene testing, and the
dosage of warfarin can be adjusted
accordingly.
available from the larger pathology labs at
Psychiatry is another area where
pharmacogenetics will play an important
role in the future, Professor McKinnon
believes. Clinicians will be able to match
differences in a person's biochemistry differences in their levels of chemical
neurotransmitters in their brain for
example - using genetic testing, so their
use of antidepressants and other drugs
can be customised.
being prescribed that don’t work in certain
quickly GPs and other clinicians will adapt
patients, and less treatment needed for
to using pharmacogenetics. It means more
toxic side effects in others.
training for GPs who’ll need to improve
It is expected that pharmacogenetics is
going to be most useful where a drug has
serious side effects at a dose not much
greater than the therapeutic dose, where a
drug is particularly expensive (so it’s
important to know the drug will work), and
where there is known to be a great deal of
variation in a drug’s effectiveness.
Nevertheless genetic testing of drugs is
still a relatively new field and isn't yet in
widespread use.
There are many issues still to be sorted
out; such as what drugs should be tested
and at what stage of treatment.
Also - does the cost justify the benefit?
Some, such as the older tests involving the
cytochrome P450 (CYP) family of liver
enzymes, (which break down many
commonly used drugs) are commercially
“The drug itself may be subsidised by
a cost of a few hundred dollars. But others
the Pharmaceutical Benefits Scheme but
can cost thousands of dollars and are only
the test isn’t covered by Medicare, so there
available through research centres.
needs to be a better alignment of funding
Conversely, there are huge potential
cost savings in the form of fewer drugs
There are some drugs where it’s
generally accepted that it makes sense
from a cost benefit point of view to screen
individuals before giving the drug, says
Professor McKinnon.
They include mercaptopurine and
azathioprine (another thiopurine used in the
treatment of solid tumours and other
conditions such as inflammatory bowel
disease). “With these drugs there's a good
argument that we should be doing genetic
testing before we start treatment to give us
an idea of how the patient is going to react
to them,’ he says.
for the drug and the test,” he says.
Another issue is how well and how
their understanding of genetics to get to
the point where they become used to
ordering genetic tests for drugs as an aid
to prescribing.
Associate Professor Leslie Sheffield is
a clinical geneticist with Genetic Health
Services Australia, and at the Royal
Children's Hospital in Melbourne. He has
been interpreting genetic tests for 25
years. He says there are now tests
available for about 30 per cent of all the
drugs in a physician’s armoury (most not
yet commercially available but used in
research labs).
He predicts GPs will eventually
But for most other drugs, there isn’t yet
enough evidence that pre-treatment
screening saves money in the longer term.
“We need more studies done before we
can make those decisions,’ he says.
“We are still unravelling the genetic
embrace pharmacogenetics because it will
take much of the hit-and-miss out of
prescribing.
He’s in the process of setting up a
service that will give GPs and other
clinicians access to information about what
differences that underlie the variation in
pharmacogenetic tests are available and
response from person to person. So there
for what drugs. The service will be
are plenty of challenges” he says.
accessible via a web site that he hopes will
To complicate matters, most of these
tests aren’t eligible for a Medicare rebate.
be online about April this year. The address
is www.genesfx.com.
PATHWAY_11
disciplines in depth
Back to basics
THE MOST RECENTLY RECOGNISED OF THE PATHOLOGY DISCIPLINES, GENETICS IS SET TO HAVE
A MAJOR IMPACT ON THE FUTURE OF MEDICINE, AS LOUISE MARTIN-CHEW FINDS OUT.
enetics is described in the RCPA
history, Pathology: Professional
Practice and Politics, as the “Cinderella of
disciplines”.
G
It is a surprisingly apt analogy with its
“rags to riches” connotations. Following
what Dr Ron Trent, the inaugural
Chairman of the Genetics Advisory
Committee, RCPA, describes as the
“genetics to genome revolution”, the subspeciality is poised to give a unique and
new focus to important health issues in
the community, becoming an integral part
of every medical discipline.
“Genetics will change the future for
inherited disease absolutely”, says Dr
Michael Buckley, chief examiner in
Genetics for the College.
12_PATHWAY
Over recent years, medical
professionals will have noticed the
increasing interest in this area, with almost
every conference now featuring a genetic
strand. Yet this discipline has only been a
recognised part of pathology and the
RCPA since 1996.
success of the Human Genome Project.
This international tour de force,
coordinated by the U.S. Department of
Energy and the National Institutes of
Health, brought scientists together
between 1990 and 2003, to identify the
20,000 genes in human DNA.
The training program in laboratory
genetics is available in three different
areas - cytogenetics, biochemical
genetics and molecular genetics. Since
1996 the diversity of the training required
in genetics has grown with the curriculum
now including the need to understand
clinical genetics, which includes aspects
of genetics counselling and analysis of
genetic information in the clinical setting.
It also determined the sequences of
the three billion chemical base pairs that
make up human DNA.
The exponential increase in interest in
genetics can be tied intrinsically to the
The information from the project has
been stored in extensive databases and
research is ongoing.
The Human Genome Project’s success
has stimulated the creation and rapid
growth of the field of genomic medicine
within pathology making the development
of an understanding of genetic material on
PHOTO CREDIT: ELIZABETH ADAMS
Marcus Hinchcliffe
4th year trainee
Registrar in Molecular Genetics,
Royal Prince Alfred Hospital, Sydney
a large scale possible. Importantly, the
Project has also resulted in the
development of improved tools for data
analysis.
have always been interested in molecular genetics and was
I
In the area of molecular medicine, the
new knowledge base has already led to
an improved diagnosis of disease.
keen to understand the science better, so after my residency at
the Royal Brisbane Hospital I went back to university to do a
Masters in Molecular Biology. I began training in molecular
Increasingly, detailed genome maps
are aiding scientists seeking genes
associated with a myriad of genetic
conditions. These include, for example,
myotonic dystrophy, fragile X syndrome,
inherited colon cancer, Alzheimer's
disease, and familial breast cancer.
genetic pathology at the Department of Molecular and Clinical
Genetics at the Royal Prince Alfred Hospital in Sydney in 2005.
Genetic knowledge is rapidly expanding, there’s a lot to keep
up with and I find that very stimulating. Increasingly, molecular
genetics will become central to medicine. Personal genome
profiles will become standard within the next ten years. There
will be wide impacts upon diagnostics, cancer profiling and
Diagnosis based on the presence of
specific genes heralds a new era of
molecular medicine - characterised less
by treating symptoms and more by
looking to the most fundamental causes
of disease.
individualised prescribing.
It still amazes me that the complexity of life can be simplified
to the combinatorics of a four letter DNA code.
The clinical side of our department consults with families
mainly on an outpatient basis. I work on the diagnostic side.
Dr Buckley has a special interest in
muscular dystrophy where genetics is part
of routine management.
“Parents want to know first what it is,
secondly if they can stop it happening
again and thirdly if it is a consequence of
their actions. So far we can answer
questions one and two. We classify the
disease according to gene mutation. If
parents are willing to go down the track of
falling pregnant and having the necessary
analysis and termination, yes we can stop
it happening again.”
Blood/DNA is sent off to the relevant laboratory. (In Australia
each lab specialises in a number of tests). At RPA we specialise
in the haemoglobinopathies, as well as a number of other
heritable conditions.
I will complete my training in 2010. My exams are mid 2008
and then I’ll do the PhD component of the RCPA molecular
genetic course. I will be looking at non-coding RNA in the
human brain using high throughput sequencing technology.
>
PATHWAY_13
“Genetics will change the future
for inherited disease
absolutely”, says Dr Michael
Buckley, chief examiner in
PHOTO CREDIT: PAUL JONES
Genetics for the College.
But diagnosis is just part of the
genetics story.
information now available, according to Dr
Trent.
Understanding the role of certain
genes and the significance of their
presence, medical researchers will also be
able to devise therapeutic regimens based
on a person’s genetic profile. They will be
able to augment or even replace defective
genes through gene therapy. Rational
drug design, control systems for drugs
and pharmacogenomics “custom drugs”
are other benefits currently under
development.
The trend to automate analysis and
the development of microarray analysis
has allowed, researchers to identify
individual genes, to look at any single
gene and have access to the information
from it concerning particular disease.
As Dr Trent notes, the sequencing of
the human genome began with modest
ambitions but has had revolutionary byproducts, albeit more complex than
originally anticipated.
“Humans have 20,000 genes. The
pinot noir grape, just sequenced, also has
20,000 genes. Humans are obviously
more complex. We need to ascertain how
it all works, how it interacts with the
environment. We need answers to these
questions.”
Advancements in genetics have been
possible in a large part by the technology
developed to manage the bonanza of
14_PATHWAY
Previously this was too complicated or
time consuming. It was also vulnerable to
human error.
In Australia, new machinery has
allowed developments in the revolutionary
areas of personalised medicine and
predictive medicine.
Personalised medicine, working with
an individual’s genomes, allows the
development of drugs and medications
that work best for that individual. Given
their genetic profile, the practitioner may
select which category of drugs puts them
at least risk and maximum benefit.
Predictive medicine allows analysis of
an individual’s DNA to identify genetic
markers that signal that person’s
predisposition to particular diseases.
Identification of such genetic mutations
prior to the disease causing any
symptoms, enables a person to take
preventative or control measures, such as
is the case with women with the BRCA1
and BRCA2 genes for breast and ovarian
cancers.
As Dr Trent suggests, “[Because of
this technology] we can predict the
possible consequences for the individual,
and this possibility, for genetics, is huge.
A handful of conditions have marker
genes, and as the technology improves
even bigger profiles of people’s genetic
make up will be a possibility.”
But this is far from a straightforward
process. Added to the difficulties inherent
in identifying the genetic markers of
disease, researchers have to also
determine how well that genetic marker
predicts the disease and whether any
action can or should be taken. And then
there is the ethical debate about the risks
versus benefits of this type of testing.
While the way forward is not without
its challenges, Dr Trent says informatics
will have an important role to play. The
sequencing of a genome and the
depositing of this information within a
database still requires interpretation, and
today, most of the genome information in
the databases remains unintelligible. He
Kym Mina
indicates that better informatics and
algorithms will make more sense of this
information in the future, and more
training in the clinical genetics area will
be required to interpret the vast amount
of data that will be generated.
While there has been a small increase
in the number of trainees in this field of
pathology, there are insufficient trainee
positions funded by governments to cope
the demand for genetic pathologists.
“The workforce will have to be
educated, to become more savvy
concerning genetic issues. Otherwise the
level of testing required and the numbers
of clinical geneticists needed will become
unsustainable. There are important
questions which need to be addressed in
terms of these workforce issues as
genetics becomes part of every medical
discipline,” Dr Trent says.
Genetics, as the Cinderella of the
pathology disciplines, has well and truly
arrived at the ball.
As a direct result of all the advances
in knowledge and technology, genetics is
playing an increasingly important role in
the diagnosis, monitoring and treatment
of diseases. Its revolutionary nature and
importance is such that genetics is
poised to become arguably the foremost
1st year trainee
Registrar in Molecular Genetics,
PathWest, Perth
studied medicine at The University of Western Australia and
completed my intern year in 2000. I worked as a resident at the
Royal Perth and Sir Charles Gairdner Hospitals but then took
some time away from medicine and had two children (now two
and five years of age). At the same time I worked toward my
PhD (completed end 2006) in Public Health (epidemiologic
methods). My training and work as a registrar in Molecular
Genetics immediately followed.
I
I am employed by PathWest which has laboratories (for both
molecular genetics and cytogenetics) in the public hospitals here
in Perth, so I rotate through different hospitals for my training. At
the moment I am working at Sir Charles Gairdner Hospital, but I
have also worked at Royal Perth Hospital and King Edward
Memorial Hospital during 2007.
While there was no direct relationship between my PhD topic
and laboratory genetics, when the opportunity to do this job
arose I found it irresistible. I have always found molecular
biology and genetics interesting, even at school, but had not
worked in the area previously. I am naturally analytical and
methodical and hence genetics and laboratory work fit well with
both my personality and interests. Genetics is also very
appealing because of its relative newness in comparison to other
fields of pathology and its growing medical relevance and
applications.
I have now been working in this position for one year and I
am enjoying it immensely. This is a new position and as a result
we’re all learning; primarily about how best to train a genetic
pathologist, but secondly about how such a pathologist might fit
into a complex and expanding genetics workforce here in WA.
science of the 21st century.
PATHWAY_15
in profile
Family matters
IF YOU OR YOUR GP HAS EVER SUSPECTED THAT YOUR
DNA MIGHT INCLUDE A HEREDITARY RISK OF CANCER,
THEN YOU’VE PROBABLY BEEN REFERRED TO A
FAMILIAL CANCER SERVICE. AND EVEN IF YOU DON’T
LIVE IN THE SAME STATE, THERE’S A GOOD CHANCE THE
SERVICE YOU HAVE VISITED HAS BEEN INFLUENCED BY
THE WORK OF THE SOUTH AUSTRALIAN SERVICE,
JUSTINE COSTIGAN MEETS GRAEME SUTHERS, THE
MAN BEHIND THE CUTTING EDGE APPROACH TO
FAMILIAL CANCER.
riginally specialising in paediatrics in
O
Sydney, where he grew up, Graeme
Suthers wasn’t thinking of pursuing a
career in genetics. But after a young
patient with homocystinuria (an inherited
deficit of amino acid metabolism) piqued
his interest, Dr Suthers changed track to
specialise in the field that has since
inspired a life-long interest in DNA and
gene technology.
Combining an interest in both clinical
and research work, Dr Suthers went on
to complete a PhD in Fragile X syndrome
at the Women’s and Children’s Hospital
in Adelaide and further research at
Oxford University. Returning to clinical
work, he was subsequently accredited as
a specialist clinical geneticist in 1993
and, more recently, as a genetic
pathologist in 2002.
16_PATHWAY
But it’s his work in the field of familial
cancer that has clearly dominated the last
ten years of his career. In 1998 he
established the Familial Cancer Service in
South Australia where he remains
Program Director to this day.
“By the mid 1990s, there was growing
awareness that a tendency to develop
cancer could be familial,” says Dr Suthers,
explaining the reasons for establishing the
service. “And instead of clinical
geneticists always being paediatricians
dealing with children and reproductive
issues and so on, the geneticists had to
start making some linkages with the
clinicians and services operating out of
adult hospitals. And that was novel. That
really hadn't happened very much. We
also saw a growing demand from patients
saying we want to come and get our
genetic situation sorted out. In South
Australia, as elsewhere, there was a rising
tide of referrals to talk about familial
breast cancer and familial bowel cancer.”
When Dr Suthers established the
service it was one of Australia’s first and
quickly became a leader in its field - an
achievement that his peers readily
attribute to Dr Suthers’ powerful
combination of vision and drive.
“Graeme saw very quickly that clinical
genetics was becoming a sub-specialty,”
“It was Graeme’s vision that got
[the Familial Cancer Service]
going and he has worked very
hard and very successfully to
bring so many different people
together to work at such a very
PHOTO CREDIT: TONY LEWIS
high standard.”
says Professor Eric Haan, Head of the
South Australian Clinical Genetics Service
who first met Dr Suthers when he came to
South Australia to do his PhD.
Haan, “and Graeme’s delivery of an
integrated service to patients has been
one of his most important contributions
(to genetics) so far.”
“It was Graeme’s vision that got [the
Familial Cancer Service] going and he has
worked very hard and very successfully to
bring so many different people together to
work at such a very high standard.”
At the heart of the Familial Cancer
Service is the role clinicians and
counsellors play in helping people come
to terms with the knowledge they may
have an increased risk of cancer.
“The Familial Cancer Service has been
an Australian leader,” continues Professor
For those with only a basic
understanding of science or medicine,
being confronted with the thought of a
pending serious disease can be daunting.
Not only does the idea of a potential (or
actual) health threat cause alarm, but
understanding the genetic process and
the risks to yourself or your family can be
a challenge.
One of Dr Suthers’ strategies to help
his patients understand how genetics
works is to highlight the universality of
mutations. When patients understand that
PATHWAY_17
>
“Cancer is generally perceived to be something that comes out of the blue and strikes
people at random. A more realistic view is to recognise that cancer is the result of a
slow burning fuse, and we all have a fuse that is burning.”
the corrosion of one’s individual genetic
heritage is intrinsic to every one of us, it
can help minimise the anxiety of a birth
defect or the word ‘cancer’.
RCPA urges
National Genetics Framework
As he laconically explains it, “Your
genes are becoming rusty.”
“I think that we still have a major job
to do in terms of giving cancer better
press, if I can put it that way,” says Dr
Suthers.
“Cancer is generally perceived to be
something that comes out of the blue and
strikes people at random. A more realistic
view is to recognise that cancer is the
result of a slow burning fuse, and we all
have a fuse that is burning. And the thing
that varies is the rate at which it burns, or
how long the fuse is. Cancer is an
inevitable consequence of being alive.
Cancer is one of the ‘privileges’ that
comes from living in a peaceful developed
society.”
One of the most rapidly changing
specialties, keeping up to date with
advances in technology and new
information is a necessity.
“It’s a bit scary to see how quickly
your carefully nurtured skills and
knowledge become out of date in this
field. You have to keep reinventing
yourself. Once you’re a cardiologist or a
respiratory physician, you’re always pretty
much a cardiologist or a respiratory
physician. But in genetics, you need to
reinvent how you perceive your discipline
and your skills. And it does require quite
constant footwork, I think, to maintain
your usefulness as a clinician.”
The speed of change also impacts the
challenges for the specialty as a whole.
While ethical frameworks for the medical
profession are being developed and
refined, private enterprise simply speeds
ahead.
“It hasn't taken long for the field to
explode well outside the reach of clinical
geneticists. We now have all sorts of
health care providers and laboratories and
commercial companies doing genetic
testing and they don’t necessarily know or
18_PATHWAY
he RCPA is calling on the federal government to develop a National
Genetics Framework to deal with urgent issues relating to the future of the
specialty including; regulation and external quality assurance for genetic
testing; the collection and interpretation of data; the development of an
appropriate framework for making ethical decisions; and the creation of a
national register of funding for genetic tests.
T
Also the College is concerned at the lack of long term planning for the
management and growth of genetics.
Currently there are eleven qualified Genetic Pathologists in Australia, with
few training positions available and a lack of Clinical Geneticists and Genetic
Counsellors.
Genetics is a rapidly changing specialty and the potential for it to
challenge how we look at healthcare is considerable.
Testing DNA for the degree of genetic fragility and degradation is now
possible (though still experimental) and has the potential to reduce the burden
of degenerative diseases in the community. Yet who will benefit from this
technology, and who should pay for it?
Although many of these issues are currently being addressed by the
NHMRC Human Genetics Advisory Committee, the AHMAC Clinical, Technical
and Ethical Principal Committee, the RCPA Quality Use of Pathology Project
and the PSTC/RCPA Alternative Funding Proposal, the RCPA is urging the
Government to create a National Genetics Framework to ensure consistency
of testing and ethical guidelines across Australia and to develop a national
framework for planning.
want to know about the sorts of ethical
himself occupied until retiring a year ago,
concerns, training and mindset that was
Dr Suthers “looks at the big picture and
being inculcated by those at the forefront
of research during the 1980s.”
The ethical considerations of DNA
takes on the issues with drive and
enthusiasm - which is what you need if
testing is just one of the many reasons
you are going to take on the hospital
why Dr Suthers is promoting the concept
system.”
of a National Genetics Framework (see
box) as part of his role as Chairman of the
RCPA Genetics Advisory Committee.
Professor of Molecular Genetics at the
Dr Graeme Suthers is the program director of
the South Australian Familial Cancer Service,
senior visiting consultant in clinical genetics to
a number of teaching hospitals in Adelaide,
University of Sydney, Ron Trent, says that
and consultant genetic pathologist to the
Dr Suthers has always showed leadership.
State’s largest public sector laboratory (IMVS)
As the incoming Chairman of the
and is the Chairman of the RCPA Genetics
Committee, a position Professor Trent
Advisory Committee.
NT-proBNP
The Power of Standardisation
“NT-proBNP... showed the best power, compared with the other immunoassays...
for separating healthy individuals from patients with mild symptoms of heart failure.” 1
s Acute diagnosis/differentiation of CHF 2
s Prognosis of CHF and risk prediction 4
s Diagnostic aid for LV Dysfunction 3
s Monitoring of CHF therapy 5
1000
951
BNP/NT-proBNP Levels (pg/mL)
900
Roche Elecsys proBNP
800
700
600
500
400
Abbott AxSYM BNP
proBNP cut-off – 125 pg/mL
342
300
266
222
200
Biosite Triage BNP
133
100
130
95
BNP cut-off – 100 pg/mL
Bayer BNP
64
0
Normals
NYHA I
NYHA II
Data taken from Product Package Inserts
Troponin T, NT-proBNP assays standardised from Point-of-Care to high throughput systems.
cobas® 6000
Elecsys®
High throughput
laboratory test
cobas h 232
Point of Care
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Roche Diagnostics Australia Pty. Limited ABN 29 003 001 205 PO Box 955 Castle Hill 1765 Australia Ph: (02) 9860 2222
1. Clerico et al. Clinical Chemistry 2005;51(2):445-7. 2. Januzzi JL et al. Am J Cardiol 2005;95:948–954. 3. Gustafsson F et al. Heart Drug 2003;3:141-146.
4. Kragelund C et al. New Engl J Med 2005;352:666-75. 5. Richards AM, Troughton RW. Eur J Heart Fail 2004;6(3):351-4.
PB3299/02-08
COBAS and COBAS H are trademarks of Roche. ©2007 Roche Diagnostics
testing testing
THE
OF
PCR
DISCOVERED BY ONE OF SCIENCE’S MORE COLOURFUL
CHARACTERS, POLYMERASE CHAIN REACTION HAS CHANGED
THE FACE OF MEDICAL DIAGNOSIS AND DNA DETECTION.
BIANCA NOGRADY REPORTS..
ix months before the 1993 Nobel
Prizes were due to be announced,
Kary Mullis’ mentor, University of
California Berkley biochemist Joe
Neilands, suggested to him that “you’d
make it easier for the [Nobel] committee
to give it to you if you didn’t talk to the
press so much”. Not that Mullis’ work
was in any way controversial - far from it.
He had developed the polymerase chain
reaction; a technique for amplifying
segments of DNA that was soon to
revolutionise molecular biology.
S
What had Neilands on edge was his
protegé’s openness about his use of LSD,
and to a lesser extent, his enthusiastically
proclaimed fondness for women and
surfing. Thankfully, the Nobel Committee
saw fit to overlook these apparent
transgressions, and in 1993 awarded
Mullis the Nobel Prize in Chemistry for his
discovery of the polymerase chain
reaction.
Mullis is an intriguing character.
Raised on a farm in rural North Carolina,
he studied chemistry then completed a
PhD and lectured in biochemistry, before
joining biotechnology company Cetus
Corporation as a DNA chemist. While
working here, he made the discoveries
that led to the polymerase chain reaction.
But far more interestingly, he has also
been tabled as an expert witness in the
O.J Simpson murder case (although was
never called to the stand), has stirred
controversy with his views on climate
change and the link between HIV and
AIDS, has been quite forthcoming about
his use of LSD in Berkley during the 60s
and 70s, apparently believes in astrology,
and is a keen surfer.
Kary Mullis’ entire Nobel autobiography
is unusually dedicated to a portrayal of his
family and upbringing. At the very end of
the document, a single, brief sentence
acknowledges his momentous role in
scientific history: “I worked as a
consultant, got the Nobel Prize, and have
now turned to writing. It is 1994.”
What this sentence fails to capture is
the significance of his discovery, and why
it was judged worthy of one of science’s
greatest accolades.
“It has been absolutely
transformative,” says microbiologist Dr
David Smith, Head of the Division of
Microbiology and Infectious Diseases at
PathWest Laboratory Medicine WA.
PCR allows scientists to locate within
a mess of DNA and RNA a short
sequence of base pairs that is unique to
the organism they are trying to detect. A
reaction is then set in motion to multiply
this stretch of DNA or RNA over and over
again until it reaches a concentration high
enough to be detectable, or usable for
other purposes.
The ready identification of DNA and
RNA through PCR testing has wideranging applications from prenatal
screening to testing of adults for
susceptibility to diseases such as breast
and bowel cancer. It can be used to help
predict a patient's response to a
particular drug, or provide more accurate
diagnosis of diseases such as cancer
helping with prognosis and therapeutics.
PCR testing also enables rapid genetic
identification of infective micro-organisms,
a process that is now standard for a
range of infections from chlamydia to
pertussis.
PATHWAY_21
>
PCR is also extremely sensitive and extremely specific,
meaning that it will detect even the smallest amounts of a
DNA sequence, and will only detect that exact sequence.
As simple as it may sound, this
approach has enabled a quantum leap in
progress. Compared to conventional
detection methods, PCR enables
detection of organisms that are dead or
degraded, difficult to culture, present in
levels too low to detect with conventional
methods, in a wide range of samples, and
can now be done within a matter of hours.
The PCR process consists of two
stages (see box). In the first stage, the
DNA of the sample is heated to separate
it into single strands, then the mix is
cooled and special DNA primers are
added to seek out a short sequence of
DNA that is unique to the organism being
tested for. Once those primers find and
lock onto their target, an enzyme is added
to create multiple copies of that particular
target. By repeating this entire process of
thermal cycling again and again, scientists
can amplify that unique DNA sequence to
a level where it becomes detectable.
The second stage involves adding
DNA probes that will bind to that
sequence, and which are tagged to allow
their concentration to be assessed.
When PCR was in its early days, each
of these steps was done separately and
would take several days to complete.
“You used to have to put them into
the thermal cycler, then leave it to run for
30-40 cycles and then you took them out
of that machine and put them onto gels to
read them,” Dr Smith says. “With realtime PCR machines it’s actually
monitoring as it goes through.” This
means the machine is calculating levels of
your target sequence as it replicates it,
and can alert you as soon as a target level
has been reached. Cycling times have
also improved considerably, so now each
thermal cycle to denature and anneal the
DNA strands and primers takes around
one minute. Within just a few hours, the
original target sequence of DNA can be
copied several million times.
This not only enables detection of
organisms or features of those organisms,
22_PATHWAY
it can also provide a valuable source of
genetic material for use in other
experiments - DNA cloning. “PCR can
also be used to generate material which
you can use to further characterise that
organism,” Dr Smith says.
In pathology, PCR has a number of
applications. It can be used to detect a
wide variety of genetic diseases, the
amplification enabling pathologists to
recognise insertions, deletions or
mutations that characterise certain
hereditary diseases such as Duchenne
muscular dystrophy.
“It’s very useful for detecting bacteria
or DNA viruses, because you can amplify
the small amount of signal material there is
to give you a measurable piece of DNA,”
says microbiologist Professor Peter Coloe,
head of Applied Sciences and professor of
biotechnology at Melbourne’s RMIT.
Even when that signal material is
thousands or even millions of years old,
PCR can still be used. In a Jurassic Parkstyle scenario, DNA has been extracted
from insects preserved in amber more
than 20 million years ago, and amplified
up into useable quantities by PCR.
Ancient Egyptian mummies have also
been probed for the DNA remains of the
pathogens that plagued them, and PCR
used to diagnose their ailments several
thousand years after they died. Using this
technique, scientists have been able to
posthumously diagnose tuberculosis from
a tiny fragment of lung tissue taken from a
mummy.
Unfortunately for this Egyptian, the
diagnosis may have come a little too late,
but the diagnosis of tuberculosis in
modern times has also benefited from
PCR. Mycobacterium tuberculosis - the
bacteria that causes the disease - is
particularly slow growing, which means
diagnosis by conventional means can
take a long time. In contrast, PCR doesn’t
require the bacteria to be cultured, so a
diagnosis using nucleic acid detection
takes just a few hours.
While Mycobacterium tuberculosis
might be slow growing, at least it can be
cultured. Other pathogens, such as
hepatitis C, have proven extremely
difficult to culture. However PCR’s ability
to detect even the tiniest amount of
bacterial or viral DNA without requiring
culture means it has become essential for
diagnosis of diseases such as hepatitis C.
It is also enabling researchers to, not
only diagnose, but learn more about a
pathogen, providing information that may
affect management of the infection. Drug
resistance is a particular concern when
treating diseases such as HIV. The
prevalence of drug-resistant HIV is currently
estimated at around 10% of new infections,
so detecting that resistance early can make
a significant difference to the choice and
efficacy of antiretroviral medication.
“Researchers can do a virtual
phenotype to work out the likely
resistance to antiretrovirals,” Dr Smith
says. “They use PCR methods to amplify
up the viral RNA and then from the
sequence of that RNA they can tell
whether it’s likely to be resistant or not.”
The same technique has also been used
to determine whether a particular strain of
the H5N1 influenza virus is likely to be
resistant to a particular neuraminidase
inhibitor - a class of drugs that includes
oseltamivir (Tamiflu) and zanamivir
(Relenza).
PCR is also extremely sensitive and
extremely specific, meaning that it will
detect even the smallest amounts of a
DNA sequence, and will only detect that
exact sequence.
“In pathology, it’s going to give you
ways of detecting very low levels of
organisms and you’ve got a level of
specificity that you might not have had by
conventional microscopy or culture,” says
Professor Coloe. “It gives you a high level
of specificity because you’re using
primers that will only bind to specific
regions where the DNA is a perfect
match.”
What is PCR?
“PCR is one of the techniques used for what we call nucleic acid detection
test,” says Dr David Smith. “What that means is that we detect the RNA or
DNA of the nucleic acid rather than, in the case of infectious diseases, the
organisms.”
However that extreme sensitivity can
also be a problem. “You can occasionally
detect levels of organisms… in such low
concentrations that they might not
constitute a disease problem,” Professor
Coloe says. “That becomes an issue
when you’re dealing with things like
water and looking for the presence of
things like Giardia - there might be
extremely low levels, you pick them up
but whether it constitutes a clinical
problem is questionable.”
It also means PCR may detect the
presence of a dead organism that is long
past being a biological threat. “If the
organism is still there in the sense that it
hasn’t been degraded, the DNA is still
there but the organism is not alive, but you
can still get a positive response,” he says.
But, there is an upshot to this - PCR is
particularly useful in situations where
samples haven’t always been kept in
optimum conditions, according to Dr Smith.
“The organism doesn’t have to be
alive, which means it’s particularly good
for samples where there are difficulties in
storage or transport,” Dr Smith says. “This
is a big advantage in testing in remote
areas where it’s very difficult to get live
organisms, particularly things like viruses
which tend to be fragile.”
So what is the future for PCR testing?
Dr Smith believes the next step will
likely be to make the test more
transportable. “How do we make these
tests more accessible?” he asks. “At the
moment, they’re confined to relatively large
laboratories, so how do we make them
easier to deliver in small laboratories?”
Making the test more transportable will also
enable its use in very remote areas or even
in scenarios such as on the battlefield.
However Professor Coloe says PCR is
not likely to reach the stage of being a
bedside test any time soon because of
the need for the amplification process.
“Remember that PCR still relies on the
temperature cycling,” he says. “In the
pathology laboratory that’s easy to do but
The technique has a variety of applications. As well as diagnosing
hereditary and infectious diseases, PCR can also be used for DNA cloning
for sequencing, identification of genetic ‘fingerprints’ used in forensics and
paternity testing including, as well as the functional analysis of genes.
But how is it done?
o start with, you need to know the genetic sequence of the particular
organism you are looking for in a sample. That information is easily
obtainable from public ‘libraries’ of DNA and RNA sequence data, such as
GenBank in the US, European Molecular Biology Laboratory's European
Bioinformatics Institute and the DNA Data Bank of Japan. “You’re looking
for parts of the sequence of the organism which are found in all strands of
that organism and which are only found in that organism; usually an area
between 80-200 base pairs in length,” Dr Smith says. The next step is to
create smaller fragments of DNA about 20 base pairs in length that are
designed to pair with either end of your larger sequence - these are called
primers.
T
These two ingredients, plus the enzyme DNA polymerase, are then
combined in a thermal cycler, which first raises the temperature high
enough so that the double-stranded DNA and primers denature, or peel
apart into single strands. The cycler then lowers the temperature to allow
the strands of primer to anneal, or bond, to their target at one or the other
end of the target sequence on the larger DNA strands, creating a collection
of single stranded DNA with a primer attached.
Now the DNA polymerase comes into play. Starting from one end of
each primer, this enzyme reads back along the single strand of DNA,
copying as it goes. After repeating this process several times, the end
result is two double-stranded copies of the target DNA sequence. The
whole process is then repeated again, and each time it is repeated, the
target sequence is copied.
“Commonly you’d use anywhere between 30-50 cycles, so you end up
with a lot of material… but once you amplify it you have to know you’ve
amplified the product you’re interested in,” says Dr Smith. This is done by
adding in a probe that binds to a specific section of the DNA and is tagged
with a particular enzyme label or fluorescent tag that can be easily
detected and measured.
at the bedside you’re not going to go
thanks to improvements in technology
through a PCR amplification process.”
and biochemistry. It’s hard to know
However PCR may be used to produce
whether the man who is credited with
the material that might be used in a hand-
developing PCR could fully appreciate the
held device, for example to detect the
impact his discovery has since had on
presence of herpes simplex virus in a cold
biological research and medicine.
sore.”
PCR has come a long way in terms of
speed and efficiency since its invention,
His reaction to the announcement that
he had won the Nobel Prize gives some
indication - he went surfing.
PATHWAY_23
close up
Human chromosomes. Coloured
scanning electron micrograph (SEM) of
a group of human chromosomes.
These structures occur in the nucleus of
every cell in the body, carrying genetic
information in the form of DNA
(deoxyribonucleic acid), arranged in
discrete segments known as genes.
Apart from the sex cells, every human
cell contains 46 chromosomes, 23
inherited from the father and 23 from
the mother. The chromosomes shown
here have replicated themselves during
cell division and so consist of two
identical strands (chromatids) linked at
their centre by a structure known as a
PHOTO CREDIT: ANDREW SYRED / SCIENCE PHOTO LIBRARY
centromere.
spotlight on disease
Metal
detectors
THERE ARE DISEASES WHERE THE
CAUSE IS UNKNOWN, WHERE THE
DIAGNOSIS IS DIFFICULT, AND
WHERE THE TREATMENT IS
COMPLEX AND EXPENSIVE.
HAEMOCHROMATOSIS
IS NOT ONE OF THESE
DISEASES.
SO WHY THEN, DESPITE A KNOWN CAUSE, A RELATIVELY STRAIGHTFORWARD TESTING
PROCEDURE AND A SIMPLE TREATMENT, ARE THERE PEOPLE WITH THE DISEASE REMAINING
UNDETECTED UNTIL THEIR ORGANS ARE IRREVERSIBLY DAMAGED, AND WHY ARE MILLIONS OF
DOLLARS BEING WASTED ON THE INAPPROPRIATE TESTS? MATT JOHNSON INVESTIGATES.
hink of seven friends to whom you are
not related. The odds are one of you
is carrying a single mutation of C282Y.
amount and, with no natural way to
C282Y is a common mutation of the
HFE gene which, until the 1990s, lay
undiscovered on chromosome six, but
has, for millions of years, been controlling
how much iron is absorbed from food.
body needs.
T
Individuals without the mutation
absorb only about 10% of the iron
contained in the food they eat: a
sufficiently wasteful process that
combined with a nutritionally poor diet
puts many people at risk of iron
deficiency.
In contrast, those with the C282Y
mutation absorb up to three times that
26_PATHWAY
excrete that much iron, it can accumulate
to levels more than 20 times what the
There are now two known mutations
of the HFE gene: C282Y and H63D, and
while a single mutation of either may
increase your iron absorption and storage,
it probably won’t accumulate sufficiently
to develop haemochromatosis, the
disease associated with too much iron.
But if you are homozygous - that is
you have two copies of the mutation,
one inherited from each parent - then
it’s likely you will be struck with
symptoms that can range from barely
noticeable to debilitating and perhaps
even eventually fatal.
The most common cause of iron
overload, hereditary haemochromatosis, is
also the most common genetic disorder in
Australia, affecting an estimated one in
every 200 to 300 of the population.
Because of its genetic nature, as many as
25% of the siblings of haemochromatosis
sufferers will also develop the disorder.
The symptoms of haemochromatosis
are both common and vague, and don’t
usually present in men until their mid 30s,
a decade or two before women who are
partially protected by the iron lost during
menstruation and pregnancy in their
reproductive years. The most frequent
One North American study found one in three people with iron overload had met with more
than 11 doctors before receiving the correct diagnosis.
With so many of the initial symptoms being attributable to other conditions, and because
excess iron damages organs slowly, the disease was often well established with irreversible
organ damage having already occurred before the diagnosis was made.
symptoms of haemochromatosis are joint
pain and fatigue, but they can also
include abdominal pain, loss of sex drive,
and shortness of breath.
Because there are few characteristic
or reliable symptoms that differentiate
haemochromatosis from other conditions,
diagnosing the disease is notoriously
difficult.
One North American study found one
in three people with iron overload had met
with more than 11 doctors before
receiving the correct diagnosis.
With so many of the initial symptoms
being attributable to other conditions, and
because excess iron damages organs
slowly, the disease was often well
established with irreversible organ
damage having already occurred before
the diagnosis was made.
Not surprisingly the discovery of the
genetic cause of the disease and the
establishment of an accurate test for the
HFE mutations was expected to radically
improve the management of the disease.
But a misunderstanding about the
test’s ability to link non-specific
symptoms to a definitive diagnosis has
led to widespread inappropriate use of the
genetic test according to David Ravine,
Professor of Medical Genetics at the
University of WA and genetic pathologist
at PathWest at the Royal Perth Hospital.
Professor Ravine and his team
recently conducted an audit of requests
for HFE testing submitted to their
laboratory.
The audit took 187 HFE test requests
and, by referring to hospital notes or
conferring directly with the doctor who
requested the tests, the audit tried to
determine if the tests were appropriate
and could therefore provide accurate
results.
The audit found that up to 57% of
HFE test requests are made for
inappropriate reasons. And in more than a
third of cases there was not enough
clinical detail in the requests for his team
to provide an accurate interpretation of
the result.
“When it was created the HFE test
was assigned a Medicare item number
and laboratories set themselves up to
conduct the test, so it very quickly
became routine,” Professor Ravine
explained. “It became like a routine
sodium test, but it’s actually a very
different type of test.”
“The interpretation of this test is totally
dependent on the clinical indication that
prompted the test. You can have a very
different report on the same result
depending on why the test was ordered,”
he said.
The problem, according to Dr Ravine
is that the link between the gene mutation
and the disease is far less perfect than
people appreciate.
“When the genetics of
haemochromatosis were first discovered
the basic view was that it was one gene,
one mutation, and you’ve got iron
overload,” he explained.
Organs affected by
haemochromatosis
Liver
As the major site of iron storage, the liver is often the first
organ to display the effects of haemochromatosis. Pain,
swelling and cirrhosis can all develop and the disease
increases the risk of liver cancer.
Heart
Cardiac failure can occur with very little tissue iron
deposition but it can also occur suddenly once the iron
levels have reached extremely high values. Once it
appears, heart function tends to rapidly deteriorate.
Hormonal
Diabetes is common in people with haemochromatosis as
iron accumulates in the pancreas. People develop overt
diabetes mellitus requiring insulin therapy. Excess iron can
also cause pituitary dysfunction and reduced sex hormone
production that can lead to infertility.
PATHWAY_27
>
Haemochromatosis
before Chronic Fatigue
Researchers have called for doctors to exclude
haemochromatosis before diagnosing and
commencing treatment of Chronic Fatigue Syndrome
(CFS). Although also a symptom of liver failure and
cirrhosis, fatigue has proved the most common
symptom present at diagnosis of haemochromatosis.
“That’s not the case. The link between
genotype and iron overload is not
perfect,” he said. “There are actually
several genes involved and since that first
discovery our awareness of the nuances
that go with that are increasing.”
Interestingly, the message coming
from Dr Ravine’s and similar studies is for
doctors to use older tests to identify
patients with iron overload before they
search for the cause of the accumulation.
“Serious iron overload is pretty
uncommon when compared with the
number of people with HFE mutations,” Dr
Ravine said. “One in four of us are carriers
of the various mutations, so just testing
for that will identify a lot people who don’t
actually have the disease.”
Dr Ravine’s position aligns with the
Medical Benefits Scheme indications for
requesting a HFE test, with the return of
at least two positive tests for elevated iron
result before requesting genotype testing.
“If you’re thinking haemochromatosis,
measure the iron first, then if that comes
back positive, then test for the gene,”
reinforced Professor Ravine.
The serum transferrin saturation test
and serum ferritin concentration tests
used to assess iron levels in the blood are
both sensitive and reliable tests that
geneticists described as phenotypic - that
is, they show patients who actually have
the disease rather than just having the
genes that can cause it.
28_PATHWAY
But the dilemma faced by Dr Ravine
and his associates is to not create a
situation where the prevalence of the
disease is underestimated.
“Significant iron overload may be
uncommon, but it’s still being
underdiagnosed, so we still want to get
doctors thinking about it,” he said. The
best chance patients have for a diagnosis
is when they build a relationship with a
single doctor who can conduct tests in a
logical order.
Professor Ravine has been
encouraged by the response of doctors to
his study but is concerned there is no
system in place to change the way the
test is ordered.
“We identified a misunderstanding
about the clinical utility of the genotype
test,” he said, “and having spotted that,
the solution is to educate doctors. But
that’s a long term, major undertaking - a
generational change and in the meantime
we’re spending millions inappropriately.”
Massachusetts General Hospital in the
USA also identified this problem and,
according to Professor Ravine, has
instituted a better system.
“They make sure someone talks to the
doctor so we know why the test was
requested,” he explained.
“This allows the pathologists to
integrate the genotype results with the
clinical indications. It’s been hugely
successful,” he said, adding that the
program had also proved very popular
with physicians.
“It’s a collaborative approach that
helps the doctor understand what are the
best tests for the condition they are
seeking.” But he is pessimistic about it
being introduced in Australia.
“The system doesn’t permit this sort
of interaction here, and while it would be
expensive it’s probably not as expensive
as what we’re currently doing.”
Compared with the complexity of
interpreting genotype test results, treating
haemochromatosis is startlingly
straightforward and effective.
Ridding the body of excess iron
simply requires removing blood the same
way it is drawn from donors at blood
banks.
Based on the severity of the iron
overload, 500ml of blood is to be taken
once or twice a week for several months.
Blood ferritin tests conducted periodically
monitor iron levels and when they reach
the low end of normal the withdrawals are
reduced in frequency. The treatment
needs to continue indefinitely but it will
usually prevent further organ damage.
Because early detection and treatment
are so effective, a number of researchers
have proposed widespread screening for
haemochromatosis would be costeffective depending on the type of testing
conducted.
Testing for blood iron is relatively
inexpensive but it has to be done twice to
confirm a diagnosis while, as has already
been shown, HFE gene testing will
capture a large number of people who
don’t have the disease.
Associate Professor Martin Delatycki,
Director of the Bruce Lefroy Centre at the
Murdoch Children’s Research Institute
and also Clinical Geneticist at Genetic
Health Services Victoria, is one of the
many researchers trying to find the most
effective screening plan for
haemochromatosis.
“One of the first issues raised in any
form of genetic screening is the stress of
knowing you have a predisposition to a
condition that you may never develop,
and that it might impact on your ability to
get insurance,” he explained.
But the results of the Haemscreen
study conducted by Professor Delatycki in
which 11,000 participants were assessed
for anxiety and health perception before
and after genetic testing found a genetic
predisposition to haemochromatosis ,
indicated those who tested positive were
not anxious about the result.
In a difficult process Professor
Delatycki was also able to reach an
agreement with the health insurers to not
discriminate against these individuals.
The greatest impediment to screening
remains cost.
Professor Delatycki has recently been
granted funding to conducted a health
economic study into the cost benefit
“In the end it’s in everyone’s interest
to prevent the disease,” he said.
relationship of testing just such a group.
Since that study Professor Delatycki
has also been involved in a study which
found 28 per cent of men in their 60s who
were homozygous had very significant
disease.
until then, Professor Delatycki is reinforcing
This, according the Professor
Delatycki contradicted earlier studies that
had predicted only 1% would by severely
affected.
haemochromatosis, but we’d like to pick
“It’s a strong indicator for genetic
screening,” says Professor Delatycki who
wants to take advantage of the fact
haemochromatosis is rare before 30 years
of age.
“Young males traditionally don’t go to
GPs, so screening them in high school
may be feasible as it virtually captures the
entire population.”
But those results are years away and
the need for early detection by GPs.
“There’s good evidence GPs are
thinking more and more about
up more people earlier so we need to
keep reminding doctors to have a very
low threshold for requesting iron studies,”
he said.
“Until screening starts that’s still our
best way of helping these patients.”
GPs NOTE: This article is available for
patients at http://pathway.rcpa.edu.au
Your
Partner in
Clinical Genomics
Enabling Clinical Genomics
WORLD RECOGNISED
ACCREDITATION
Drug Metabolism / Pharmacogenomics
Microbial Identification
Email: appliedgenomics@agrf.org.au
Cancer
- Chromosome Copy Number
- Linkage Analysis
- Array CGH
- Loss of Heterozygosity
PATHWAY_29
In the eye of the beholder
hile for many, the Renaissance
W
masterpieces are the epitome of
fine art, for some scientists, the works
represent a hidden fascination with the
anatomy of the human brain.
Writing in the Journal of the Royal
Society of Medicine (2007;100:540-543),
four UK scientists describe examples of
hidden symbolism in Renaissance
paintings by artists such as Rafael,
Michelangelo and David. The theory is
that the artists used the imagery to
conceal their fascination with the
The artistic anatomical representation
anatomical discoveries being made at
was first suggested by another scientist,
the time, as such interest was often
FL Mershberger, who believed the cloth
branded as sacrilegious by the clergy
and figures behind God in Michelangelo’s
who were likely to have commissioned
Creation of Adam resembled the sagittal
the artwork.
section of the human brain.
Heart disease
on the rise
he decline in coronary artery disease
T
seen in western countries in recent
times may have come to an end, trends
seen in autopsy findings suggest.
Epidemic of diabetes and
cardiovascular disease
In a US study of 425 autopsies of
people who died of unnatural causes
between 1981 and 2004, researchers
found that the temporal decline observed
in the grade of coronary disease ended
A
drive to the nearest shop,” the article
says.
rampaging through the South Pacific, the
"Even if you go into a store in a
remote village you'll find shelves of Spam
and corned beef," the piece quotes Dr
Jan Pryor, the director of research at the
Fiji School of Medicine, as saying.
Spam-fuelled epidemic of diabetes
and cardiovascular disease is
UK’s Daily Telegraph reports.
The Telegraph notes the tragedy of a
region once famed for its lithe inhabitants
driven to health crisis by a luncheon meat
“lampooned by Monty Python and
spurned by British shoppers.”
“Where once islanders ate fish,
vegetables and coconuts, burning off
excess calories by casting nets from
canoes and farming small plots of land,
now they eat tinned, processed food and
30_PATHWAY
after 1995 “and possibly reversed after
2000.”
The findings are based on data from
death certificates and pathology reports
among Olmsted County residents aged
16 through to 64 years. Writing in the
Archives of Internal Medicine (2008;168:
World Health Organisation figures
show that eight of the world’s 10 most
obese nations are in the region.
264-270) the study authors say their
Nauru, former home to Australia’s
“Pacific Solution” detention centre, tops
the table with 94.5% of adults defined as
obese. Similar problems are repeated
across the South Pacific.
declines in heart disease mortality may
findings provide “some of the first data to
support increasing concerns that
not continue.... The extent to which
recent trends are attributable to the
epidemics of obesity and diabetes
mellitus awaits further investigation.”
Prostate
predictor
genetic test for hereditary prostate
A
cancer appears to be around the
corner, with the successful identification
of an array of gene markers for the
disease.
In a study of over 4000 Swedish men,
researchers from the Karolinska Institute
and their American colleagues found the
presence of a number of genetic
variations, along with family history of
prostate cancer increased the likelihood
of the cancer more than nine-fold.
They found 16 single nucleotide
polymorphisms, in five different regions of
chromosomes 8 and 17 were common to
men with prostate cancer.
While the findings published in NEJM
online (Jan 16, 2008) need to be
validated and refined, efforts to develop a
genetic test are underway, say the study
authors.
Glucosamine Magnesium
prevents
interaction
gallstones
R
egulatory authorities are warning
doctors of an interaction between the
alternative arthritis remedy glucosamine
and warfarin.
In its recent bulletin (Volume 27,
February 2008), the Adverse Drug
Reactions Advisory Committee (ADRAC),
says it has received 10 reports of patients
showing an increase in their INR after
starting glucosamine.
The mechanism behind this interaction
is still unknown, but the effect of
glucosamine on warfarin activity is
consistent with reports received by other
drug monitoring bodies overseas,
including the WHO Collaborating Centre
for Drug Monitoring.
ADRAC recommends patients on
warfarin should have their INR checked
within a few days and no later than two
weeks after they start or increase their
dose of glucosamine.
agnesium-rich foods such as nuts
may help prevent gallstones, US
researchers say.
M
In a prospective study of more than
42,000 men over a 17 year period,
researchers at the University of Kentucky
found that men with higher intakes of
magnesium-containing foods had a
significantly lower rate of symptomatic
gallstone formation.
The findings, published in the
American Journal of Gastroenterology
(103:375-82), were supported by other
evidence that magnesium deficiency
causes dyslipidaemia and insulin
hypersecretion, which may promote
gallstone formation, said the study
authors.
6minutes is a daily online newsletter and
website for Australian doctors, including
general and specialist practitioners, published
by Reed Business Information.
GET MORE THAN JUST
THE TAX BREAKS
Convenient and flexible health insurance
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when you buy hospital insurance, but you still want to choose health
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For all the information you need and to join visit
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www.doctorshealthfund.com.au
PATHWAY_31
cutting edge
High
expectations
DR KATHY KRAMER LOOKS AT THE ROLE OF
GENETIC TESTING IN PRENATAL SCREENING FOR
FETAL ABNORMALITIES - ITS BENEFITS,
LIMITATIONS AND POTENTIAL.
any pregnant women worry about whether the
M
baby is okay, and now doctors can offer so
much more than soothing words.
There aren’t tests for all the potential problems,
but general screening for some serious conditions and special testing for families with particular risks have become a routine part of Australian prenatal care. In
fact, the Human Genetics Society of Australia and the
Royal College of Obstetricians and Gynaecologists both
recommend that screening be offered to every woman.
Professor Eric Haan is a clinical geneticist at the Women's
and Children's Hospital in Adelaide and an expert on prenatal
genetic testing. “There are basically two time points when
screening is offered for Down syndrome, and the screening picks
up some other abnormalities, such as trisomy 18.”
“First trimester screening involves an ultrasound at 11 to 13 weeks
looking at nuchal translucency (the width of a fluid-filled space at the
back of the fetal neck) plus a blood test at nine to 13 weeks.”
It picks up about 90% of Down syndrome pregnancies but
falsely suggests one in twenty pregnancies is affected when really
it is fine.
The screening calls for a skilled ultrasonographer but also
relies on the expertise of biochemists, like Dr Michael Sinosich,
Scientific Director of Prenatal Testing at Sydney’s Sonic Health
Care.
“We really need both diagnostic modalities, biochemistry
and ultrasound, monitoring different parameters to get an
optimal performance in assessment of feto-placental
wellbeing,” he says.
32_PATHWAY
In the laboratory, pathologists look
at a range of different chemicals known as markers - which are produced
Another side of the story
by the placenta or fetus, and are
detectable in the mother’s blood.
Marker levels can change when there is
an abnormality such as Down
syndrome. The results are used to build
a picture of how likely it is that a
pregnancy is affected by the condition
for which it is being screened.
There’s nothing magic about the
number produced by screening, he
says, and different labs can produce
slightly different numbers depending on
how many biochemical markers they
test for, what machines they use and
the software they employ. “For example,
we use four markers but other units
may use two,” he says.
Second trimester screening involves
a blood test at 14 to 20 weeks (ideally
15 to 17 weeks). It picks up only about
75% of Down syndrome pregnancies
and wrongly identifies about 7% of
normal pregnancies as being at
increased risk.
“Being told about an increased risk
often causes anxiety in women at the
time and during the pregnancy and
even after the birth, and they often
remember it very vividly as something
that had a big emotional impact,”
Professor Haan says.
About 80% of women found to have
an increased risk choose to go on to
invasive diagnostic testing, he says, and
most decide not to continue with the
pregnancy if the baby is affected.
An ultrasound is also recommended
for all women at 19 to 20 weeks. This is
not part of Down syndrome screening; it
checks the well-being of the pregnancy
and can detect physical malformations
in the baby, some of which may be due
to underlying genetic problems.
“Once you know your risk is high,
you have to decide, ‘am I going to sort
this out or not?’ And the main way to
sort out whether the baby does or does
not have the condition after first
>
etal genetic testing can also help
women who have recurrent early
miscarriages or a late miscarriage or
stillbirth.
F
Fetal pathologists have a particular
role in diagnosing lethal inherited
disorders. In these conditions, there is a
1-in-2 to 1-in-4 chance of future
pregnancies being affected. It’s
important to distinguish these from
chromosomal disorders, where the
recurrence rate varies from 1-in-3 to 1in-100, and environmental, sporadic and
uterine disorders which don’t tend to
recur.
Dr Adrian Charles is a perinatal and
paediatric pathologist at the King
Edward Memorial Hospital in Perth.
There are two scenarios that typically
call for his services.
The first is where an apparently
normal pregnancy ends in miscarriage or
stillbirth and the parents consent to an
autopsy. “We say, this fetus has a range
of abnormalities that amount to this type
of syndrome and then we ask for that
test to confirm the diagnosis. Sometimes
the parents are tested and/or future
pregnancies are tested early in the
pregnancy with possibility of interrupting
the pregnancy if it’s abnormal,” Dr
Charles says.
A question arises over whether
chromosomal testing should be offered
after all pregnancy losses. “A large
number of the first and early second
trimester miscarriages are due to
chromosomal abnormalities, so we could
check for these but the test costs a few
hundred dollars and most of these will
not recur, so is not indicated on every
case,” he says.
“There is growing pressure from
parents to try to find an answer: you
have to be thoughtful of the health dollar
but it does ease the parents’ minds to
identify a cause.”
The second scenario is where
prenatal screening has identified an
abnormality and the pregnancy has been
terminated. Often there is little doubt
about the diagnosis, and a post-mortem
examination merely confirms, for
example, that the fetus has features
consistent with Down syndrome.
However, anatomical pathology
comes into its own when the diagnosis
can only be made by examining specific
tissues. For example, an ultrasound may
identify cystic kidney disease but only a
pathologist can determine which of the
many disease types is involved. “We
look at the fetal tissues under the
microscope and this can give us a very
clear idea, even though we don’t have a
specific genetic test, about what the
recurrence rate is, whether it’s 1-in-4 or
1-in-2 or pretty low.”
“We try to get the abnormality clearly
determined so the parents can be
counselled.”
Dr Diane Payton, an anatomical
pathologist, does similar work at the
Royal Brisbane Hospital.
“If we can recognise an intact fetus,
we do an autopsy,” says. “If it is very
tiny, we look at the external appearance
and may attempt an internal examination
and certainly examine the cells. From
around ten to twelve weeks, we can do
an excision and check the internal
organs.”
She takes tissue for basic genetic
testing in most cases. When she has a
specific diagnosis in mind - for example,
such as cystic fibrosis - she may take
additional cells from relevant organs.
However, careful thought is required,
because there isn’t a screening test for
all the potential different genetic
problems. “Unless I can suggest what I
want them tested for, there’s not much
we can do.”
“This is a specialised area in which I
usually seek advice from clinical
geneticists,” she says. “Many of the
investigations are highly specialised and
are only performed in selected
laboratories in the country.”
PATHWAY_33
trimester screening is chorionic villous sampling
[CVS] at the end of the first trimester or
amniocentesis at the beginning of the second
trimester, or amniocentesis after screening in
the second trimester.”
If there is an increased risk of a
chromosome problem - say, because the
woman is more than 35 years old or because a
previous pregnancy has had a chromosome
abnormality - women can skip screening and
go straight to a definitive (rather than screening)
chromosome test. This is either CVS from 10 to
11 weeks or amniocentesis at 15 to 16 weeks.
Many couples choose CVS because the result
Goodbye to invasive testing?
oth chorionic villous sample and amniocentesis can trigger a
B
miscarriage, albeit very rarely, so researchers are looking for safer
ways to perform fetal genetic testing.
“It is known that there are a small number of fetal cells, shed by the
placenta, that circulate in the mother’s blood,” geneticist Professor Eric
Haan says. “And for many years attempts have been made to isolate
these cells for genetic testing. It is clearly possible to do so, but so far
reliable, universally applicable and cost-effective testing in early
pregnancy has not been developed.”
Preimplantation genetic testing, performed on cells removed three
is available at a much earlier stage in the
day after fertilisation, is an evolving field which may allow couples to
pregnancy.
implant only embryos free of a particular gene.
The most commonly performed genetic test
IVF Australia, on its website, points out that this is really only
is a chromosome test using cells taken from
appropriate for couples where there are already family members with
the placenta (via CVS) or shed from the baby
serious inherited genetic disorders. “Worldwide researchers are
and floating in the amniotic fluid (via
questioning whether the same technology will allow improved embryo
amniocentesis). “The chromosomes can be
selection prior to embryo transfer, and hence improve pregnancy rates
seen and counted, so it is a very reliable test
for Down syndrome because they can see the
extra chromosome,” Professor Haan explains.
per cycle for all couples having IVF treatment. The small studies
performed so far have not been of a large enough size or been designed
to answer this question accurately.”
DNA tests for literally hundreds of different
heritable genetic conditions can also be done.
The first such test was performed in 1978 for
sickle cell anaemia, Professor Haan says.
The most common tests these days are for
thalassaemia, fragile X syndrome, cystic
fibrosis, Duchenne muscular dystrophy and
MIRAX LIVE RT
infantile spinal muscular dystrophy. If doctors
Combine the advantages of
conventional microscopy with
the power of Live Robotic
Telepathology
don’t know which gene is causing a problem,
there may be other ways to test for the disease;
for example, if the disease involved a specific
enzyme, a chemical pathologist may be able to
measure enzyme levels.
However, prenatal genetic testing is not
without risk. CVS and amniocentesis can
Full remote slide access and microscope control.
trigger a miscarriage, although the risk is small.
An occasional problem with CVS occurs
when some, but not all, of the placental cells
contain a genetic mutation. This is called
‘mosaicism’. It usually affects only the placenta,
not the baby, so amniocentesis is
recommended to check the baby’s cells.
However, even a normal amniocentesis does
not definitely exclude mosaicism.
“Also, some abnormalities may not be
detected because they are too small to be seen
reliably with a light microscope,” Professor
Haan points out.
So, women and their partners need to know
that chromosomal testing is not foolproof.
34_PATHWAY
Carl Zeiss Pty Ltd
Unit 13, 2 Eden Park Drive
North Ryde NSW 2113 Australia
Nationwide: 1300 365 470
Email: micro@zeiss.com.au
http: www.zeiss.com.au
foreign correspondence
Wisdom in the Solomons
SOLOMON ISLANDS PATHOLOGY IS SET TO COME INTO ITS OWN WITH A LITTLE HELP
FROM SOME AUSTRALIAN FRIENDS. KIM COTTON REPORTS.
he appointment of the Solomon
Islands’ first indigenous pathologist
last year brought an unexpected bonus. A
group of top Australian pathologists and
medical scientists travelled from
Queensland to the South Pacific
archipelago to establish an anatomical
pathology laboratory.
T
For more than 20 years, Pathology
Queensland (a branch of Queensland
Health’s clinical and statewide services)
has been the Solomon Islands’ major
referral centre for pathology support.
Services have included general pathology
as well as diagnosis of surgical
histopathology and cytology specimens.
However, with the appointment of Dr
Roger Maraka to Honiara’s National
Referral Hospital (NRH), it seemed logical
to the group that a laboratory be
established, in which the pathologist
could practise.
The five experts who traveled to the
nation’s capital Honiara last September
for the mission included Dr Michael
Whiley, director of Pathology Queensland,
Professor Konrad Muller, state director of
anatomical pathology, Bob Partridge,
regional coordinator and Leigh Owen
supervising scientist at Pathology
Queensland Central Laboratory, and Dr
Stephen Weinstein, director of pathology
at the Gold Coast Laboratory Group.
Dr Weinstein, who has worked on
similar projects in East Timor and
Vanuatu, said the team operated as a
“well-oiled machine”. Tasks undertaken
included installation of histology
equipment and communication software,
staff training and the development of a
quality assurance program and support
framework for Dr Maraka’s ongoing
professional development.
“For the first time ever the surgeons
and doctors can get the results then and
there, and view their own tumours and
cancers without having to have them sent
to Brisbane,” Dr Weinstein said.
The Solomons is made up of almost
1,000 mountainous islands and coral
atolls divided by nine provinces spread
across 28,000 square kilometres. It has a
population of just over 500,000 with about
40 per cent aged less than 15 years.
The NRH has about 280 beds and
about 20 medical staff. The NRH
laboratory has haematology, biochemistry
and microbiology with a separate malaria
laboratory. Apart from Honiara, there are
two small laboratories in the provincial
capitals of Auki (Malaita province) and
Gizo (Western province).
Dr Weinstein said the 750 annual
histology cases that are produced in the
Solomons are likely to rise with the
operation of the local service. Dr Maraka
also conducts about two forensic
autopsies a month and runs a fine needle
aspiration clinic.
Pathology Queensland donated
equipment to fit out the histology unit,
which was freighted with the support of
PATHWAY_35
>
“Just the fact that the
pathologist can function as an
important member of the
clinical team… that makes a
difference for the hospital and
the medical staff”
the Lions Club. The donation was made
possible by the Ipswich lab and Mr Owen
was instrumental in organising the
logistics of moving the equipment,
including a processor, microtome and
embedding station to the Solomons. Two
local Solomons technicians who had been
previously trained in Brisbane were
reskilled in operating the equipment as
well as correct specimen handling and
packaging, Dr Weinstein said.
“At the end of the week they were
producing diagnostic-quality histology
slides to the delight of Dr Maraka. This
will mean that the majority of histology
from the Solomons - all of which was
previously sent to Brisbane will be
reported locally in the future,” he said.
Oral cancer, including cancer of the
buccal mucosa, tongue and gums, is one
of the most common malignancies in the
Solomon Islands - due to the popularity of
chewing the carcinogenic betel nut. Liver
cancer is also common courtesy of the
high prevalence of hepatitis.
Cervical cancer, still common due to
poor screening practices, will continue to
be diagnosed in Brisbane - in part
because of the absence of a local
cytoscreener and the issue of quality
36_PATHWAY
assurance in Pap smear reporting
procedures.
present these [findings] in clinical
meetings.
With the greatest morbidity in the
Solomons being caused by infectious
diseases, namely malaria and
tuberculosis, the unit was unlikely to have
an “immediate earth shattering” effect on
the nation’s health, Dr Weinstein said.
Also the benefit of having a local
pathology service was hampered by the
lack of radiotherapy and chemotherapy,
limiting the ability to treat diagnosed
malignancies beyond surgical excision.
However, the fact that a resident
pathologist can now discuss with
colleagues diagnostic reports - and
receive results much faster - will have a
major impact on staff professional
development and morale, he said.
“Just the fact that the pathologist can
function as an important member of the
clinical team… that makes a difference for
the hospital and the medical staff,” he
said.
“For medical staff in the National
Referral Hospital it’s important that they’re
not isolated, they feel they are not
stranded without support,” Dr Weinstein
said. “Now they can come down and ask
if they can see the tumour or have Dr
Maraka point out an interesting feature
and discuss whether surgical margins are
clear, did they excise it completely… they
can interact with the pathologist in the
laboratory and the pathologist can also
Another tenet of the project was the
development of a strong continuing
education model for Dr Maraka to ensure
his professional development remains
current and that he also feels supported
collegially.
“Continuing education for the
pathologist himself is a major problem in a
place like the Solomons because
pathologists should ideally not practise
alone. They should have a colleague to
whom they can show interesting cases,
bounce them off and also cover for them
when they go on leave,” Dr Weinstein
said.
The pathologist will continue to send
to Brisbane all cases requiring second
opinions and special stains, and in
addition send a randomly selected five
per cent of his work for quality assurance
purposes. Twice a year, with the support
of the Pathology Queensland SERTF Trust
Fund, Dr Maraka will also visit Brisbane to
refresh his skills.
Previous page: Young Solomon Islanders in traditional dress
Blood sample being taken by a Pathology staff member.
During the visit, Dr Whiley gave a
presentation to the medical staff grand
rounds on the relevance of point of care
testing and the Istat instrument to remote
locations. Dr Weinstein presented recent
Solomons’ histology cases reported in
Brisbane and also breast cancer and
screening.
Such an experience for the Australian
contingent brought an insight into the
health problems and health system of a
small developing country and “a great
sense of satisfaction to help out there”,
Dr Weinstein said.
“Even be it in a very limited way and it
helps set up long term relationships
which are valued greatly.”
Dr Weinstein suggested opportunities
are available for Australian pathologists to
take on unpaid locums in the Solomon
Islands as a means of experiencing a
different health system as well as
affording them a break from the normal
routine.
Meanwhile, Dr Maraka reports the
new lab is going well.
Dr Weinstein said. “He is able to
repair any equipment locally; he is in
email contact when he needs advice and
is energetically getting down to work.”
Left to right this page:
Selling taro at the market in Honiara
Mr Michael Aiko, histotechnologist preparing diagnostic slides;
Dr Roger Maraka, Solomon Islands first Indigenous pathologist with
Professor Konrad Muller, Pathology Queensland's Director
of Anatomical Pathology
Fact file
The majority of Solomon Islanders (80 per cent) rely
on subsistence agriculture and fishing.
There were 90,606 reported malaria cases in 2003
with 71 deaths.
TB rates in 2005 were 142 per 100,000.
The prevalence of betel quid chewers is 76.8 per
cent.
Life expectancy for Solomon Islanders is 63 years
(at 2004).
Sources: AusAID, World Malaria Report 2005, WHO Global Health Atlas TB
Country Profile, American Journal of Tropical Medicine and Hygiene, Human
Development Report 2006.
PATHWAY_37
finance finesse
$$$
STEADY AS YOU GO
- Super Planning
It has been a roller coaster ride for investors in the
share market this financial year. Not only has the
year seen the start of the biggest changes to our
superannuation system in 20 years but the share
market has reached its highest levels in history and
then tumbled by more than 20 per cent.
This much anticipated correction to the share
market had been expected for some time but the
magnitude of the fall surprised many. Consequently
because of various international influences the ride
in the short term future looks anything but steady.
However for superannuation investors it is perhaps
not as alarming, as the effect of these corrections
have been felt more by those investing money in a
relatively short term volatile market. As
superannuation is a longer term investment these
Greg Lomax
Greg Lomax is the CEO of Huthnance Lomax
Accountants and Financial Advisors in
Chatswood NSW. He is a regular columnist for
the Sydney Morning Herald and Melbourne
Age and other professional magazines.
38_PATHWAY
fluctuations are expected in the overall investment
cycle and with a well chosen portfolio of
investments, the magnitude of any fall can be
cushioned by diversification.
It is important to remain calm and focused on the
underlying benefits that can be gained from
choosing super as the number one investment
strategy in today’s uncertain and volatile markets.
The following four steps will help
you utilise superannuation as your
main investment choice:
1.
Achieve your maximum tax
breaks via super for this and
future years.
2.
Review your current super
arrangements to ensure you are
in the right fund and determine
if a self managed fund is right
for you
3.
Understand the impact of
accessing your super benefits
and the hot tax strategies this
creates for over 60’s.
4.
Review the basic estate
planning issues involved with
the increased financial
resources now in super.
1. ACHIEVE MAXIMUM TAX
BREAKS VIA SUPER
The new superannuation rules changed
the maximum deductible contribution to
$50,000 per annum. However if you are
50 or over the maximum contribution is
$100,000 per annum until 2012.
This provides special opportunities
particularly for those employing their
spouses in their business where tax
deductions for super contributions can be
up to $200,000 per annum.
Also self employed practitioners can
now enjoy full deductibility on their
contributions compared to the old rule
where only 75% of the contribution was
tax deductible.
Some careful planning needs to take
place if you also receive a salary as well
as self employed income. If the salary
income exceeds 10% of the overall gross
income of the practitioner then tax
deductible contributions cannot be made.
This can usually be avoided by a salary
sacrifice arrangement or restructuring of
the employment income.
Additional contributions can be made
to super without claiming a tax deduction.
The limits on these contributions are
$150,000 or $450,000 averaged over three
years. There is no contributions tax on
these undeducted contributions.
2. REVIEW YOUR CURRENT
SUPER ARRANGEMENTS
3. ACCESS TO SUPER AND
RESULTING STRATEGIES
Now that most people are making super
their main retirement vehicle, it is
important to be aware of the manner of
investment and type of fund you have. In
particular you need to be well aware of
your own risk profile and match this to the
class of investments you use in your fund.
Many people are not aware of the
commissions and fees attached to every
contribution. A statement of advice must
be provided by an advisor when making a
recommendation so be sure to read it
closely as it must clearly state the way in
which the advisor is paid and how the
investment is managed.
You can access your super from 55 years
of age while you are still working. The
benefits you withdraw are taxable at your
marginal tax rate less a 15% rebate. Once
you turn 60 the benefits are tax free on
withdrawal.
Self managed superannuation funds
are growing rapidly in popularity for good
reason especially since the introduction of
the new super rules.
For a practitioner over 60 this is a
“must do” and presents some top tax
strategy opportunities. An example is by
contributing up to $100,000 per annum,
you receive a tax deduction against your
income and also have the ability to assist
the funding for further contributions if
needed by access to your super benefits.
This is certainly a hot strategy as it allows
a tax saving on the $100,000 of income
reducing the tax rate from 46.5% to less
than 15 per cent.
The advantages of considering a self
managed fund strategy include:
•
The flexibility of controlling the type
of investments you have in super.
•
The ability to move into a pension
mode, tax free without disposing of
any of the fund’s assets. (i.e. no
capital gains tax to pay).
•
The ability to both receive an income
stream from your super fund and
continue to make tax deductible
contributions to the same account
(i.e. no need to have separate super
funds or accounts)
•
The tax benefits from receiving
income from fully franked investments
and offset the resulting tax credits
thereby reducing the tax rate in the
fund.
•
Delay of tax payments until the
lodgement of the funds tax returns
rather than paying 15% contribution
tax on the day you make a
contribution.
•
Ability to access new products that
will allow borrowing by self managed
super funds. These are called
installment warrants and are allowed
under new Government legislation
that now extends the allowable
borrowings to any assets including
property.
While self managed super isn’t for
everyone, it is certainly worth looking at
the pros and cons as it affects individual
practitioner circumstances.
The advantage in considering this is
that the underlying super benefits in your
fund are placed into a tax free state. This
means there is no tax on capital gains or
earnings of the fund whilst it is in this
pension mode. If you have a self managed
fund in pension mode you can even get a
refund of the value of any franking credits
the fund has received.
4. REVIEW ESTATE PLANNING
ISSUES
The new super rules allow for super to be
withdrawn tax free when you are over 60.
But if you die and do not have a surviving
spouse or financial dependents, the funds
will be taxed at 16.5% when passed to
your estate.
It does not apply to after tax or
undeducted contributions you made to
the fund. This is an unfair and inequitable
treatment and one that may well be
changed in the future. In the meantime it
is prudent to speak to your advisor about
the best way for you to deal with this.
Most lawyers and financial advisors
recommend you not only have an up-todate trust deed, but an enduring power of
attorney together with a death benefit
nomination in place to assist in the tax
free release of super benefits in cases of
terminal illness. Once released from super,
the funds can be gifted to children,
relatives or other intended beneficiaries
directly or via an individual’s estate
without tax implications.
PATHWAY_39
RCPA update
Snapshot of
Pathology Update 2008
14- 16 March 2008
Sydney Convention and Exhibition Centre,
Darling Harbour
PATHOLOGY UPDATE IS TRULY A UNIQUE CONFERENCE,
WHICH BRINGS TOGETHER EIGHT DIFFERENT
DISCIPLINES OF PATHOLOGY OVER A THREE DAY
SCIENTIFIC MEETING, OFFERING SOMETHING FOR
EVERYONE.
Highlights of the 2008 program
include:
• Innovations Program on Patient
Safety
• Trainees Program
• Seven international speakers
• Six cross discipline sessions
• ‘Meet the Chief Examiner’ sessions
• General Poster Display and a
combined discipline Abstract
Publication.
www.rcpa.edu.au/pathologyupdate
40_PATHWAY
Innovation and
Trainees Program
- Friday 14 March 2008
Innovations explores professional issues
concerning pathology now and in the future.
The program starts with the RCPA Quality
Assurance Program Symposium, which will
profile a range of important developments in
quality assurance, and culminates with a
presentation by the eminent Dr Stephen Raab
on practice redesign for patient safety. The
afternoon will showcase the inestimable Dr
Chris Smith, sponsored by the Australasian
Association of Clinical Biochemists (AACB),
who is speaking on the naked pathologist
(though he will be clothed as far as we
know!). The afternoon continues with the
theme of patient safety in microbiology with
Prof David Paterson and genetics with Dr
Graeme Suthers.
Trainees Day is a great opportunity to
address aspects of the curriculum that
trainees might otherwise find difficult, as well
as providing practical, exam-oriented
sessions and workshops in the afternoon.
Talks include critical appraisal, issues around
the handling and control of laboratorygenerated data and ethics and patient
advocacy – all by prominent pathologists with
extensive experience in these areas. There is
also a session on using mindlfulness to help
deal with the stresses of being a trainee by
Craig Hassed, from Monash University who is
internationally recognised for his work on the
applications of meditation in medicine. The
afternoon includes workshops on electron
and light microscopy as well as the AP exam
review and the mock exam for part I
Microbiology candidates.
Scientific Programs
- Saturday 15 & Sunday 16 March
Anatomical Pathology has worked hard
to put together a varied and interesting
program that will have “something for
everyone”. Dr Neil Lambie, from
Christchurch, will present this year’s “An
Approach To…” lecture, on lung biopsy
for non-neoplastic lesions. The combined
Anatomic and Paediatric Pathology
seminar will feature Dr Adrian Charles
from Perth, and Prof Yee Khong and Dr
Nicholas Manton from Adelaide. The
Anatomical Pathology stream will also
include one of a number of crossdiscipline sessions this year, in joint
presentations with Genetics and with Oral
Pathology.
Chemical Pathology The program will
include a joint session with
Microbiologists to update attendees on
the latest advances in all aspects of viral
hepatitis, including a lecture on blood
tests for liver fibrosis, as well as drug
toxicity of the liver. There will also be
updates from working parties on cardiac
markers, serum urate, creatinine and
eGFR, as well as from the Australian
Pathology Lipid Interest Group. A whole
session is devoted to the Chemical
Pathology of pregnancy, and experts on
PSA and vitamin D will be bringing the
current thinking in their areas of expertise.
Forensic Pathology will include how to
distinguish real injuries from post-mortem
and decomposition artefacts, presenting
evidence in court, pros and cons of the
expert witness by two eminent lawyers,
sudden death due to alcohol, the problem
of drowning, sudden death in
schizophrenia, the toxicology of the new
anti-psychotics and the documentation of
sexual assault.
Genetics The genetic code acts as a
resource for building and maintaining the
human body, and also dictates the body's
response to a variety of external
challenges, such as infection. For this
reason, genetics is pervasive and has
relevance in every discipline of pathology.
The genetic program in Pathology Update
2008 is closely integrated with other
disciplines, including anatomical
pathology (genetics of tumours),
haematology (genetics of leukaemia), and
microbiology (genetics of susceptibility to
infection). But the novelty and broad
application of genetics also raises
particular challenges in developing and
maintaining quality assurance across
multiple disciplines, and this is the focus
of later sessions in the program.
Haematology has a program that
encompasses updates on malignant
haematological disorders with reviews of
some practical day-to-day issues of
assessing haemostasis and managing
alloimmunisation in pregnancy. Overseas
speaker Dr Wendy Erber opens the
Update with Acute Leukaemia; subclassification and markers of prognosis,
local speakers follow with topics on
individualizing therapies for childhood
leukemia. There will be a combined
session with Immunopathology on
lymphoma.
Immunopathology has a range of
highlights, including some of the top
Australian B cell biologists discuss the
application of recent advances in B cell
biology to clinical practice. There are also
talks on clinical application of some the
newer autoantibodies including antibodies
against water channels and nucleosomes
and a joint session with haematology on
lymphoma diagnosis. In addition a
session has been devoted to newer
aspects of allergy epidemiology and
diagnosis. In all a varied but very
interesting program.
Microbiology has internationally
recognised experts presenting in the areas
of hepatitis, meningococcal infections,
and new ways of preventing these
infections. Aboriginal health remains an
enormous public health issue for all
Australians, and speakers from research
institutes in the Northern Territory, and the
UK, will discuss their personal experience
and research. Microbiology impinges
upon all parts of pathology, so we have
designed the program around the needs
of all pathologists, trainees, and clinicians
from a wide variety of subspecialties.
Oral Pathology is a specialised area of
Anatomical Pathology, dealing with the
mouth, teeth, and jaws. The Oral
Pathology program commences with a
review of the Oral Pathology Quality
Assurance Program module, followed by a
series of case reports. There will be a joint
Oral Pathology and Anatomical Pathology
plenary session featuring Dr Jocelyn
Shand, an Oral and Maxillofacial Surgeon
who will talk about surgical
management of head
and neck pathology. This
presentation will enable
pathologists to better
understand the
treatment of
the various
conditions
they report in
patients.
Last but not least…
Network and Relax at
Pathology Update
As well as an important professional event, Pathology Update 2008 has a fun
and relaxing social program that gives attendees the chance to meet with other
local and international colleagues in a relaxed and informal environment. The
Update will kick-off with the Welcome Cocktail Party, ‘Jive at Five’, on Friday
March 14 with a special cocktail. The Industry dinner of the year is always one
that’s not to be missed – at Doltone House, nestled on the upper deck of the
historic Finger Wharf at the newly restored Jones Bay Wharf, Pyrmont Point.
PATHWAY_41
2008
Conference Calendar
MARCH 2008
5
13th Ottawa International Conference
on Clinical Competence
5 - 8 March
Melbourne, Australia
14
Pathology Update
14 - 16 March
Sydney, Australia
www.rcpa.edu.au/pathologyupdate
17
Focus Cytology Tutorial for
Pathologists
17 - 19 March
Sydney, Australia
Joanne.clarke@symbionhealth.com
MAY 2008
30
Cytopathology Course Singapore
30 May - 1 June
Singapore
www.med.nus.edu.sg/path/teach/cytopath2008.htm
JUNE 2008
SEPTEMBER 2008
25
College of American Pathologists
25-28 September 2008
San Diego
www.bitlifesciences.com/wsa2008
…because it’s not
just a test, it’s a patient.
6
www.anzfss2008.org.au
16
American Society of Clinical Pathology
October 16-19 2008
Baltimore MD, USA
http://www.ascp.org
29
The National Forum on Safety and
Quality in Health Care
29 - 31 October
Adelaide, Australia
www.achs.org.au/nationalfiorum08
Quality test results demand
quality specimen collection.
The BD Vacutainer® brand of
products provides a total system
for specimen collection needs. We
back our products with clinical
expertise, educational materials,
and training programs to help you
obtain the best results possible.
Pathology Update 2009
BD…over 100 years of quality
and service you can trust.
in conjunction with XXV WASPalm
13-15 March 2009 - Sydney Australia
MARCH 2009
13
The XXV WASPaLM Congress in
conjunction with Pathology Update
13 - 15 March
Sydney, Australia
www.rcpa.edu.au/pathologyupdate
42_PATHWAY
Accuracy Is Our
First Priority
The 19th International Symposium
on the Forensic Sciences
6 - 9 October
Melbourne, Australia
www.iaop.com
World Summit of Antivirals - WSA 2008
20 July 2008 to 26 July 2008
Kunming, China
Family of products
you can rely on
OCTOBER 2008
American Academy of Oral
Maxillofacial Pathology
22 - 26 June
California, USA
20
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http://www.cap.org
22
JULY 2008
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