“Genetic pathologists are able to make a diagnosis, provide an answer
to a clinical problem and contribute in a very impor...
Genetic pathology offers opportunities for increasingly powerful synergies
with other specialties within clinical and labo...
Professor David Ravine is the Foundation Professor of Medical Genetics at the University of Western Australia

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At medicine's frontier


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At medicine's frontier

  1. 1. HEALTH + MEDICINE Melody Caramins is in the fourth year of her genetic pathology training program and says she "couldn't imagine doing anything else At medicine’s frontier A REVOLUTION IS TAKING PLACE IN THE FIELD OF GENETICS, AND GENETIC PATHOLOGISTS ARE UNIQUELY POSITIONED TO PLAY A LARGE PART IN IT, WRITES TONY JAMES. PHOTOGRAPHER: MALCOLM FAIRCLOUGH + JAMES ALCOCK G enetics is the “new kid on the block” for pathologists. Hereditary aspects of disease have been recognised for and function at the most fundamental level.” been facilitated by a host of new techniques to amplify or replicate DNA and define the sequence of bases that Painting is based on just three primary centuries, but knowledge about the colours, but they can provide an infinite make up the human genome. mechanisms behind inheritance and the variety of expression. Similarly, genes Cytogenetics involves the microscopic way that genes control normal and consist of sequences of just four bases, analysis of the 23 pairs of human abnormal biological functions has but this simple code also has the capacity chromosomes. Sophisticated manipulation increased exponentially in the past few for infinite complexity. of cell samples makes it possible to check decades. for physical abnormalities such as “Developments in genetics are Genetic pathologists are at the explaining many things we never additional or missing chromosomes, or forefront of translating basic science into understood before, in every organ translocation of fragments from one clinical practice that benefits patients. system,” Dr Caramins says. “Genetic chromosome to another. Some knowledge of genetics is now pathologists are able to make a diagnosis, Cytogenetics has been the basis for essential for medical practitioners provide an answer to a clinical problem prenatal screening procedures using foetal regardless of their speciality, but genetic and contribute in a very important way to cells obtained by amniocentesis or pathologists are uniquely positioned to clinical decisions about how patients are chorionic villus sampling. Classic combine a detailed understanding of the treated.” anomalies include Down syndrome (most biology, familiarity with laboratory commonly caused by the presence of Dr Caramins is in the fourth year of her techniques and an appreciation of the three instead of two copies of five-year training program. The first three clinical application of their results. years involved working in a genetics chromosome 21), Turner syndrome (a For Dr Melody Caramins, an advanced diagnostic laboratory at Sydney’s Royal single X chromosome in a female) or trainee in molecular genetics at the Prince Prince Alfred Hospital. As part of the Klinefelter syndrome (two or more X of Wales Hospital in Sydney, the discipline training program, she is now completing a chromosomes in addition to a Y is intellectually elegant, clinically important research project on genetic control of chromosome in males). and a medical frontier. “It’s been a great platelet numbers. Other sub-specialties include career choice – I couldn’t imagine doing These small components of blood are biochemical genetics, focussing on anything else,” she says. essential in the control of bleeding. Low inherited disorders of metabolism such as Dr Caramins chose genetic pathology platelet counts, which can occur in phenylketonuria. after she started training as a surgeon, diseases such as leukaemia, sometimes Professor David Ravine and Dr and then had the chance to look at her require transfusion, which is not without Graeme Suthers both started their career options from a different angle while risk. Understanding the factors that genetics careers as paediatricians and had completing a master’s degree in design. control platelet numbers could potentially their interest piqued by a need to “Surgery was exciting, but I wondered lead to new therapies. understand health and disease at their whether it would be able to maintain its Genetic pathology is traditionally most basic levels. interest,” she says. “My experience with divided into molecular genetics and Professor Ravine is the Foundation art heightened my awareness of the form cytogenetics. Molecular genetics is a very Professor of Medical Genetics at the and function of the human body. modern science. It started with the University of Western Australia. His clinical Molecular genetics can explain that form discovery of the structure of DNA and has base is within PathWest, while his 40_PATHWAY
  2. 2. “Genetic pathologists are able to make a diagnosis, provide an answer to a clinical problem and contribute in a very important way to clinical decisions about how patients are treated.” PATHWAY_41
  3. 3. Genetic pathology offers opportunities for increasingly powerful synergies with other specialties within clinical and laboratory medicine. research straddles PathWest and the Genetic pathology offers opportunities genetic knowledge,” Professor Ravine Laboratory for Medical Genetics at the for increasingly powerful synergies with says. Western Australia Institute of Medical other specialties within clinical and It’s now possible to test for a number Research. He was impressed by the laboratory medicine. For example, of conditions that are dominantly inherited, potential power of genetics in solving anatomical pathologists are being aided including the connective tissue disorder medical problems while completing a by new molecular techniques to define the Marfan’s syndrome and hereditary Bachelor of Medical Science research mutations involved in cancer tissue. arrhythmias. project as a medical undergraduate. After Conversely, histopathology has the “The process of translating new training as a paediatrician he worked at potential to enhance greatly genetic genetic knowledge into clinical practice the Murdoch Institute and the Royal testing services for conditions such as has only just begun, but it will become a Melbourne Hospital on inherited polycystic hereditary colorectal cancer, hereditary huge part of medicine,” Professor Ravine kidney disease. From this clinical vantage breast cancer and Fragile X syndrome. says. point he saw the significance of genetics The current rapid growth of new gene- Identifying a genetic susceptibility to as a tool in all areas of medicine, not just based tests, which aid diagnosis, disease in an individual raises questions of inherited childhood diseases. prognosis and therapeutic choices, places ethics and privacy, but clinicians are faced laboratory medicine in the centre of clinical with the reality of interpreting the Moving to the Institute of Medical applications emerging from the recent information with patients, defining the Genetics in Cardiff, he retrained in genetic expansion of knowledge about the human risks, developing strategies for prevention pathology and, as director of the Medical genome and the genetic abnormalities or treatment and discussing the Genetics Service for Wales, saw how the underpinning many human diseases. “We significance of the findings for other family science could be translated into need a new generation of pathologists members. In a condition such as meaningful clinical practice. who are able to contribute to Huntington’s disease, the challenges might “The United Kingdom has a multidisciplinary clinical teams,” he says. seem overwhelming. centralised and co-ordinated health “Clinicians are focussed on clinical This disease is genetically dominant service, and is now well on the way problems, while genetic pathologists have and leads to severe neurodegenerative towards implementing the opportunities the training and experience to bridge changes, with jerky, involuntary movement for clinical practice improvement that across specialties and provide helpful and behavioural change that usually genetics provides,” he says. “Genetics is solutions”. becomes apparent in middle age. Patients relevant to all areas of medicine: there are “We also need to keep up with may have children of their own by the time interactions between genes and the colossal change. The technology is of diagnosis, and the children will have a environment in virtually all disease states. moving very quickly and is creating one in four chance of developing the Genetic pathologists need a breadth and opportunities to centralise services, but disease themselves. depth of knowledge about the scientific this needs to be thought through carefully As a clinical geneticist, Dr Graeme basis of genetics that extends beyond that as it also brings a risk of undermining Suthers has had to negotiate a path of other specialities. invaluable direct interactions between the through such challenges. “I’d advise the “They need to understand in detail the laboratory and clinicians.” children of someone with Huntington’s genetic basis of disease and be able to Education of the medical profession disease to ‘hasten slowly’,” he says. “They apply it fluently to clinical problems. They and maintaining networks between need to understand precisely why they are have to know about the methods of clinicians is an essential leadership role for having a genetic test and consider all the laboratory analysis and how to interpret genetic pathologists. One example is the possible options.” data in a clinical context, and the genetics of cardiovascular disease, a Finding they did not have the gene managerial aspects of running a rapidly developing field. “We need to would be reassuring and allow them to laboratory, including appropriate staffing empower cardiologists, general physicians lead a normal life, but if they did have the and quality assurance.” and GPs to deliver the benefits of new gene they would be faced with the 42_PATHWAY
  4. 4. Professor David Ravine is the Foundation Professor of Medical Genetics at the University of Western Australia knowledge that they would almost realise that the disease might not be Genetic pathologists work closely with certainly develop the disease. However, entirely “out of the blue” and the diagnosis the multidisciplinary team that advises the there is the prospect of substantially might have implications for their families. patient and family. If patients give consent, reducing the prevalence of the illness if “The unit of care in clinical genetics is the Dr Suthers’ unit writes to relatives to tell people with the mutation choose not to family rather than the individual patient,” them about the situation and suggests have children. he says. “We need to understand the they contact either their GPs or the unit. It “A genetic diagnosis of Huntington’s biology of the disease and the role of seems only about one in three take up the disease also has implications for the genetic testing, and communicate this in a offer, perhaps reflecting a continuing fear health-care system,” Dr Suthers says. useful way to other family members.” of cancer, a denial of risk or a lack of “There is no effective treatment, but A vital point is that genetic understanding about the scope for people need long-term support and follow- susceptibility does not mean cancer is prevention. up. Continuity of care can be invaluable. inevitable, and there are continuing Developments in genetics mean that For example, senior nurses in medical improvements in prevention and treatment. the amount of raw data now available genetics units often take on the role of “In familial bowel cancer, for example, exceeds the capacity of scientists and case managers for patients and their colonoscopy is a superb tool for screening clinicians to handle it. “We need to families, but we need the resources to be relatives at risk and removing polyps distinguish very carefully between data able to provide the services patients before they become malignant. In theory, such as sequences of bases in the genetic deserve.” no one should die from the disease,” he code and information that is applicable to Dr Suthers trained as a clinical says. “The average life expectancy in clinical practice,” Dr Suthers says. geneticist after being intrigued by a young families who adopt screening is increased “Perhaps most importantly, we need patient with homocystinuria – an inherited by 15-20 years – a remarkable wisdom to use it properly.” deficit of amino acid metabolism – he saw achievement.” He is concerned that the health system as a paediatrics trainee. Following a PhD A high genetic risk of breast cancer is has not recognised the need to provide in Fragile X syndrome at the Women’s and another area that requires extensive more resources to take advantage of the Children’s Hospital in Adelaide, research at education and counselling of affected genetic revolution, including adequate Oxford University and further clinical work, families. While high-risk genes such as numbers of doctors with appropriate skills he also qualified as a genetic pathologist BRCA1 account for a small proportion of and experience. Currently there are only and is now director of the South Australian all breast cancer cases, a woman with the four training positions funded in dedicated Familial Cancer Service. gene might have a lifetime risk as high as genetic pathology in Australasia (far short The service assists patients with a 80 per cent and could consider of requirements) while there are 17 strong inherited susceptibility to cancer to prophylactic mastectomy. laboratories that could provide training if funding was available. PATHWAY_43