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Our medical future

[ The University of Melbourne Voice Vol. 6, No. 5  3 May - 13 June 2010 ]

In a world of ever increasing computer capacity and population growth, a new realm of computational and mathematical methods is being applied to a range of societal issues as diverse as traffic management, flight simulation, drug development and health prevention. By Rebecca Scott.

Using these methods, doctors of the future will look to precision medicine and bioinformatics to assess best treatment options for patients.

“The underlying concept is that information about a patient’s protein, gene or metabolite profile could be used to tailor medical care to the individual’s needs,” says Professor Arthur Shulkes, Associate Dean (Research), Faculty Medicine, Dentistry and Health Sciences at the University of Melbourne.

He says precision medicine is becoming possible because of the ability to sequence the genes of individuals (genomics) and to measure a person’s chemical fingerprint in blood and other fluids (metabolomics).

Although, he says, currently only small parts of the genome can be sequenced routinely because of cost, in the near future it may be that whole genome sequencing will be free because of the benefits to patient care in terms of optimising treatment and predicting susceptibility to diseases. 

“To take advantage of this flood of data, an individual’s medical records must be electronic and this will add to the informatics challenge,” Professor Shulkes says.

“The data will need to be stored and interpreted and understood by the patient and clinician, which will require changes in how we train our health professionals and also how we educate the general public on issues such as disease susceptibility and their individual variability in their responses to drugs.”

The Virtual Physiological Human (VPH) is a major global health initiative that aims to provide patient-specific computer models for personalised and predictive healthcare. The University of Melbourne is a member of the global Network of Excellence of the Virtual Physiological Human. Organs being worked on include the heart, brain and musculoskeletal system and the kidney.

Professorial Fellow Peter Harris of the University’s Department of Physiology, who is a member of the Advisory Board for the VPH and was involved in the early development of the kidney model project node in Australia, says that by creating virtual organs it will enable researchers around the world to share information and medical research.

“This ultimately will enable faster delivery of drug development for a diverse range of diseases,” he says.

Researchers are excited about the opportunities for discoveries in disease prevention and patient treatment in the practice known as patient-specific medical simulation.

Dr Steven Manos, Manager, Research Services in the University’s Information Technology Services, was previously at the University College of London and involved in research that aimed to produce a unique prototype system for studying brain blood flow for hypertension.

“To understand how organisms develop and function, we need to not only understand how the constituent parts (such as cells, organs and tissues) operate, but how these parts interact, “Dr Manos says.

“By using computers, we open the door to a radically new way of treating disease; the effectiveness of drugs or surgery can be simulated and customised for a particular person by using their genes or physical characteristics as input to a computer simulation.

“In the future, the design of treatments using patient data and integrated models of cells, tissues, organs and the entire human body will be commonplace.”

The power of supercomputers and new genomic technologies will take this investigation to another level.

The Victorian Government and University of Melbourne-led Victorian Life Sciences Computation Initiative (VLSCI) is a computational facility aimed to strengthen the research capabilities and outcomes of Victorian life sciences research.

As part of a new partnership with IBM, a Blue Gene supercomputer, offering high speed and large scale processing capacity enabling scientists to address a wide range of complex problems, will be installed in the facility.

The Virtual Physiological Kidney project has been selected for the first stage of the VLSCI supercomputing facility. The project is under the direction of Dr Ed Kazmierczak from the Department of Computer Science and Software Engineering in the Faculty of Engineering.

Dr Ed Kazmierczak, Dr Rob Moss, Dr Michael Kirley and Professor Peter Harris have developed a new kidney model that, for the first time, has the potential for simulating the entire kidney as a complex system of interacting nephrons. The approximate one million nephrons are tubules inside the kidney that filter the blood and remove waste, maintain blood pressure and secrete various types of hormones.

“This new computational model will help us to understand what changes occur in the way that the kidney filters blood in the presence of chronic renal disease and consequences of the disease such as hypertension,” Dr Kazmierczak says.

So far the research community has modeled large systems of nephrons but never at this level of detail. “Our hope is to be able to model an entire kidney with one million nephrons within the next two years and be one of the first groups in the world to do it.

“A supercomputer is the only computer fast enough to simulate the onset of renal disease, which can take up to 20 years, within a matter of hours.

“The application of this research will be that future medical researchers will be able to test new drugs and the effects on drugs and have a better understanding of how the kidney operates during disease and under treatment.”

For Professor Terry O’Brien of the University’s Department of Medicine at the Royal Melbourne Hospital, Pharmagenomics – the identification of genetic markers that are predictive of the outcome of medical treatment for an individual – is a critical area if radical progress is to be made in the treatment of epilepsy.

Epilepsy is the most common serious neurological disease worldwide. Up to 40–50 per cent of patients starting a medication for the first time for epilepsy will not achieve seizure control. Uncertainty about seizure recurrence is one of the most disabling aspects of this common condition.

“Armed with more reliable predictive information for the individual, the treating clinician would be able to give tailored advice regarding treatment choices, likely outcomes and lifestyle restrictions. Currently such advice is given as ‘one size fits all’, Professor O’Brien says.

“With the increase of computational capacity now available to us, the age of individualised medicine or pharmagenomics for epilepsy has commenced.”

Utilising the computational facilities and expertise at the VLSCI, Professor O’Brien and his collaborators are working to establish a model that utilises multiple genetic markers to better predict AED treatment responses in epilepsy sufferers. 

“The identification of genetic markers that provide accurate prediction in an individual patient of their biological chance of seizure control with AED treatment would have significant clinical and societal value,” he says.

However, Professor O’Brien believes it is unlikely in complex heterogeneous diseases such as epilepsy that a single marker will satisfactorily explain treatment outcomes.

“Individual variations observed in patient response to therapy are likely to be multi-factorial; drug absorption, distribution, metabolism and variability of drug target receptors may all influence treatment outcomes – either independently or collectively. Therefore any clinically useful genomic predictor will need to consider multiple genetic variables.

“It is hoped within the next five years, we will see such predictors incorporated into routine clinical practice so that doctors can use the tools to ultimately improve the quality of life for all epilepsy sufferers.”

Professor O’Brien says, beyond epilepsy, the analytical and methodological outcomes developed in this project will be widely applicable to the development of predictive models for treatment outcomes for many other common complex diseases.

The roll out of Australia’s National Broadband Network (NBN) is expected also to play a major role providing connectivity to support in the establishment of new initiatives in electronic healthcare or e-health.

The establishment of The University of Melbourne’s Institute for a Broadband Enabled Society (IBES), is testament to the vision for the NBN to benefit society and in particular health and wellbeing in the community.

“The advent of the National Broadband Network is expected to change the dynamic of the Australian health system,” says Dr Kathleen Gray, Senior Researcher in Health Informatics in the Faculty of Medicine, Dentistry and Health Sciences.

“It will be provide essential connectivity for patients to selectively share data with health professionals (including text, radiographic images, and laboratory data) rapidly between sites, and allowing clinicians to access real time data during a patient consultation.

“In addition the NBN will enable the exploration of different interfaces and methods for medical professionals, patients and researchers to interact with critical health data.”

Research areas for the Institute include; provisions for ageing well and aged care services, such as in-home monitoring; opportunities for healthcare over distance through screen-based Internet television and other telehealth technologies; broadband support for e-collaboration for research and teaching in laboratory and clinical health sciences; and for genome-based or precision medicine.

A current IBES research grant aims to develop broadband enabled applications, such as interactive information resources and social networking to improve the management and monitoring of youth mental wellbeing.

Dr Shanton Chang, Dr Reeva Lederman and Dr Martin Gibbs of the Department of Information Systems at the University of Melbourne will work in partnership with ORYGEN Youth Health and the School of Psychological Sciences to develop a number of internet based resources for young people to address the issues of depression, first episode of psychosis (FEP) and isolation through disability.

The team will explore the development of youth specific and interactive online applications to assist with treatment decision making that includes young people. It will monitor depressive symptoms, adverse events as well as the maintenance of general mental wellbeing.

“Using an evidence-based approach and including input from, and access to, their carers and clinicians we will be able to monitor the effectiveness of these broadband-based interventions and thereby improve the management and treatment of depression in this age group,” Dr Sarah Hetrick of ORYGEN Youth Health says.

A further project will address the issues of young people recovering from their FEP, which most commonly has its onset in late adolescence and early adulthood.

“The majority of these patients experience a relapse within the first year after clinical remission and up to 82 per cent experience a relapse by five years,” Associate Professor John Gleeson from Psychological Sciences says. “The high rates of relapse in this group make it necessary to evaluate novel psychosocial interventions specific for FEP patients.”

So how will doctors and specialists of the future prepare for integrating these technologies and the growth of precision medicine into their working day?

Professor Geoff McColl, Director of Medical Education Unit at the University of Melbourne, who has played a major role in the development of the new Melbourne MD says, “The definition of precision medicine, to me, is the understanding of the patient’s perspective.”

“The health care system is going to change more significantly in the next few years than it has in the last twenty,” he says.  “Technology and medical knowledge is not going to stand still.”

“The young doctors of the future will be more challenged to analyse data and information available whilst providing the best option for the patient.”

He explains that by being exposed to the rigour of medical research and to challenging clinical environments, students of the new Melbourne medical degree will be better placed to meet needs of their patients in a changing technological environment.

“In the new Melbourne Medical Degree, I believe we have set up a program to give them a set of adaptable skills, a rigour of thinking to interrogate complexity and to stand out of the crowd of other medical graduates.”

The advent of “precision medicine” will also affect how the law views medicine, and, in particular, the care provided by health professionals. Professor Loane Skene, a health law and bioethics expert, and a member of the Australian Health Ethics Committee and Professor at the University’s School of Law, says this new form of medicine has unique implications for privacy laws.

“Precision medicine will enable medications and other treatments to be given to patients taking account of their own specific characteristics. In order to do this effectively, we will need to amend our privacy laws.

“Instead of focussing on the right of individual patients to control their personal information and not to have information about them collected or used without their consent, we should take a more holistic view.

“We should acknowledge the potential advantages for patients in having their information reordered in a secure form in a central register which can be accessed by their health professionals as the need arises.”

Professor Skene says this will minimise unnecessary repeated procedures and enable treatment to be personalised for individual patients. “Already, there have been significant steps towards a privacy regime of this type, with recent amendments to privacy legislation.”

With additional reporting by David Scott


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