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