Inspiring smarter brain research in Australia

Published in 2013, the following report outlines recommendations resulting from the Theo Murphy High Flyers Think Tank on inspiring smarter brain research in Australia.

Executive summary

Large, difficult, interdisciplinary projects are the ones that are most likely to make a major difference to society. They have the potential to affect many areas of human existence. During the past 50 years, the two most obvious examples are human flights into space and the human genome project. A research program that is constructed to answer a problem as large as these will be by definition expensive, collaborative and international in scope. But the rewards are great – the human genome project has revolutionised much of medicine, and created thousands of new skilled jobs. The US recently estimated that every dollar that was put into the human genome project generated more than one hundred dollars in outcomes

Understanding the human brain is exactly this kind of project. One purpose of the 2013 Think Tank was to determine whether we in Australia have the scientists, the resources and the will to participate in the growing international commitment to major brain research projects over the coming decade. In April 2013 President Obama announced that the United States was launching the federal one billion dollar Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative, an ambitious 10-year long research project designed to revolutionise our understanding of the human brain, which will be complemented by many, smaller American brain research projects. The European Union launched its ‘Flagship’ Human Brain Project through its Seventh Framework Programme, allocating more than one billion euros (€, approximately A$1.5 billion) to a 10-year initiative that aims to coordinate European efforts to simulate and understand functions of the human brain through the use of supercomputers (see Appendix A for more details on these two initiatives). There are slightly smaller, but equally ambitious, initiatives in China and Norway. In addition to the scientific excitement that these massive international research initiatives have generated, there is also the ‘elephant in the room’ question for us: is there a real risk that Australia will be left behind (as happened for the human genome project), while the rest of the world takes advantage of the commercial, medical, social and electronic advances that will be based on brain research?

What are the key areas that will facilitate and be represented in future research, and do we or can we have relevant strengths in these areas? Can we predict where the problems will lie, so we can focus on these places in our own research efforts? Can our researchers, who are traditionally ‘silo-based’ (working in groups isolated from each other and often competing), find ways to pool efforts and work in a mutually beneficial and collaborative research program in this area when they so rarely do so in other areas? Are we prepared as a nation to invest, when we see the massive investments from the United States and Europe, and with China waiting in the wings? These are the issues that were discussed by 60 of Australia’s brightest young scientists at the Theo Murphy High Flyers Think Tank in Melbourne in July 2013.

The Think Tank had strong representation from researchers in basic neuroscience and in neurology, neuropathology, genetics and cognitive science, which to some extent reflects research areas that are traditionally strong in Australia. Fewer attendees had experience in translating basic science into outcomes, whether in technology, medicine, or public health and ethics. Think Tank participants joined one of four groups, each focusing on a particular aspect of brain research (their four reports follow this summary). The groups were asked to identify the major research problems that face neuroscience, discuss Australia’s strengths and weaknesses in each, and off er suggestions on how we can make a realistic yet ambitious contribution to the international effort to understand the structure and function of the human brain.

Brain research is unusual in that it operates at several levels, from the molecular and cellular levels through to the study of consciousness, intelligence and executive function. The human genome project has identified all human genes, but the functions of many (especially those expressed only in the brain, perhaps half of the total number of genes) are still obscure. However, single neurons can now be analysed for gene expression patterns, and the connections made by groups of neurons can be studied using high definition structural and functional magnetic resonance imaging (MRI). The rate of advance in molecular genomics and imaging is such that we can anticipate that accurate data on the human brain’s single cell structure, gene expression and alteration, and connectedness will be available to all within the coming decade.

All of the groups agreed that the study of the brain was becoming an international focus of great importance. All groups felt that Australia was very strong scientifically in many areas, by virtue of our healthcare system and our universities and medical research institutes, although teams are often separate from one other and do not integrate and collaborate. All concluded that Australia must identify some areas where we can make a high-level, and hopefully unique, contribution if we want to remain a collaborative international player. Four areas were noted as particularly important:

  1. The understanding of higher cognitive function and intelligence (and ultimately consciousness itself ), and their relationships with the fine and gross structure of the brain, both in adults and in the complex processes that occur during development.
  2. The need to develop computer software and hardware sufficiently powerful to model brain function. The creation of a ‘bionic brain’ might require new algorithms and paradigms because the complexities might involve working in several new dimensions, and perhaps with a number of more simple animal models. This will need to be done in concert with high-level technicians, bioinformaticians and computer scientists trained specifically to work on the brain.
  3. The need to ensure that there is a seamless interface between clinical provision and research investigation, so that we can advance medical research with every patient, and so that all clinical tests and measurements (including imaging) are available to researchers. This interface will allow the translation of research endeavour into improved outcomes for patients and society.
  4. A strengthening of our resources in ethics, public health, and health services research. Ethics committees should see their role as being facilitators of research. Health services research, and the concepts of ageing and end-of-life decisions, should be included in all key discussions on cost-effectiveness of treatments and on the level of resources allocated to elderly patients who might suff er from neurodegenerative diseases such as Alzheimer’s

In Australia, our most notable weaknesses compared with Europe or the United States are the extent to which our researchers are divided into many siloed teams that compete against each other for scarce resources rather than collaborate; and the absence of long-term funding that prevents scientists from undertaking the ‘hard projects’ and diminishes the confi dence of early career researchers in building enduring scientifi c careers. In spite of our clinical strengths (in terms of well-trained doctors, nurses, paramedics, psychologists and rehabilitation therapists), we have a hospital system that often looks down on, or even refuses to facilitate, research. While we are strong in IT and programming, we do not have a fully competitive computer industry. However, we also have advantages. We have a very egalitarian healthcare system; most people in Australia with a serious neurological disorder will have ready access to tertiary care at a high standard, including contemporary diagnostic imaging and gene tests. We have an excellent university system, based for the most part on domestic students, with great strengths in neuroscience, particularly clinical neurology and neuropathology, developmental biology and imaging. Finally, we have a population and politicians who believe in and support medical research, and are willing to participate in research if given the opportunity.

The benefits

An Australian brain research program with domestic and international collaborations would have far-reaching benefi ts for both current and future generations

  1. This large proposed initiative aims to understand the relationship between the molecular and cellular events that occur in the brain and higher processes such as thinking and reasoning. There will be immediate positive outcomes in medicine, where clinicians will be able to understand more about mental illness, ageing (Alzheimer’s and Parkinson’s diseases in particular) and intellectual handicap.
  2. The findings of this research program will also tell us much about normal brain function. One area of high importance will be the study of changes induced in the brain by different environments; there is already a US study determining whether social and environmental factors can induce epigenetic changes in children.
  3. Investment in brain research will benefit the education sector (schools and universities) via new educational principles and teaching materials that will increase student achievement.
  4. There will almost certainly be significant industrial and defence outcomes, such as new services born from improved connectivity and treatments for post-traumatic stress disorder. Genuine innovation will be born from understanding the way the brain assimilates and interprets subtle signals and differentiates them from noise. The development of new products such as diagnostic tools, pharmaceuticals and other therapeutics and software or mobile computing applications will also be accelerated.
  5. Australian innovation and productivity growth will depend in large part upon the availability of competitive skills and creative intellectual capital. Participation in a global brain program will most benefit the service sector, which in Australia comprises over 65% of our GDP.
  6. We will be better able to retain excellent scientists and doctors in Australia, and attract a new intake of highly skilled researchers to work here, based on the excellence of our research. Without a competitive research environment, the best of our own doctors and scientists will leave for other countries where there are more and better opportunities.
  7. We will be able to integrate our excellence in computing, neuroscience, pathology, translational medicine, psychology and ethics, a unity that will bring benefits to other fields. We will be able to operate (more easily than most countries) in an efficient yet ethical research environment.

Recommendations

Those who attended the meeting are strongly of the opinion that Australia needs to make a strategic investment in brain research now, to enable us as a nation to share the benefits of this booming global endeavour. Strategic investment will not only afford the preservation of excellence of our current biomedical research strengths, but allow us to share the health, defence and commercial benefits that will result from the US$5 billion global venture over the next decade.

Wherever possible, Australia’s contribution should be in an area where we have advantages because of the strength of our existing research, or from other national structures such as our health system. We recognise that we represent groups with a vested interest in increasing the national investment in brain research, and therefore we propose that the Australian national brain initiative (‘AusBrain’) be coordinated by a national consortium committee that includes federal and state governments, patient support groups, information technology, the Defence Science and Technology Organisation, NICTA, the Australian Nuclear Science and Technology Organisation and CSIRO, the health and hospital systems and industry, as well as representatives of the universities and medical research institutes.

Because of the 10-year perspective for major programs of research into the brain, the discussions did not only focus on the obvious, immediate clinical targets such as Alzheimer’s disease. Over the longer time scale appropriate for this research, it is likely that areas of concern such as post-traumatic stress disorder, autism, and the interaction between genes and environment in mental illness will begin to be elucidated. The real benefits from a major commitment to brain research will be most likely to come in these areas that are presently very poorly understood. Commercial and entrepreneurial opportunities that arise might be in fields that hardly exist at present, such as epigenetics and brain/machine interfacing.

Many practical ideas were put forward. Some were simple and inexpensive ideas, such as facilitating a series of workshops that allow people from various discipline backgrounds to meet, exchange ideas and begin collaborations. The need to train scientists with experience in two disciplines (neuroscience and bioinformatics, for instance) is also a recurrent theme, as is the need to involve patient support groups in determining the research agenda. Equally important is the need to increase the number of clinicians who have experience with basic research to PhD level, and to embed a research culture in clinical training, both for doctors and for allied health professionals such as nurses and psychologists. There is a powerful argument for a national ethics framework, as at present research ethics committees are locally based and often lack a national and international perspective. Several individuals noted that it is important to free scientific research from ethics reviews that inhibit rather than facilitate important research programs, based on fears that have little substance.

‘Big ideas’ were also put forward and received substantial focus and attention. One group urged a commitment to create a ‘bionic brain’, while two others suggested large, properly funded teams with 10-year support to work on difficult, interdisciplinary projects. One such project would involve the careful study of simple animal models (such as the bee, fly or worm brain) as proof-of-concept model systems for the much larger human brain projects. The sorts of sums required for such research are large enough to make a difference and to be a fruitful contribution to global efforts (particularly if they are allocated on merit, but with an eye to ambitious, visionary research, and are committed for 10 years to a group including early career researchers). We note that the Cooperative Research Centre (CRC) structure is ideal for some aspects of ambitious brain research, as it is by nature transdisciplinary and includes a commitment to both commercial and clinical translation into practice.

Even a total allocation of the order of $250 million over 10 years – perhaps $25 million a year – would be less than 1% of the Commonwealth Government’s total commitment to research at present. We see this sum as additional to the welcome commitment that has already been made by the Government to fund dementia research with $200 million over five years. Dementia research is a small component of brain research, and will be subject to different drivers from much of what is outlined below. The meeting felt that it would be important that the new commitment (which would be known as an RFA, or ‘request for applications’, in the United States) was overarching between several federal and state government departments, and would be seen with pride as ‘whole of governments’.

Other recurrent themes were the need to be able to move seamlessly from lab to clinic to community (using, for instance, eHealth as a tool), and the involvement of the community in discussions on the ethics of neuro-research. It was noted that diseases associated with ageing (such as stroke and Parkinson’s and Alzheimer’s disease) would have a major impact in terms of numbers and funding on the community, but in some cases informative models for study may be found in neurological disorders that occur in children, including rare neurogenetics diseases. The most important point that came from the meeting was the need to ensure that new initiatives bring together people from many distinct disciplines, including neuroscience, computing and clinical research, and are firmly established within an ethical framework that is welcomed by the Australian community

In the group summaries that follow, there is also an appropriate focus on some of the broader issues facing Australian science: the need to facilitate and value, rather than ignore or prevent international links, the need to ensure that the very best early career researchers are given security of funding, the need to promote collaboration and open access to patient material and raw data, and the value that would accrue from establishing three or four CRCs specifically in these fields.

We will attempt to flesh out this proposal, but we also believe it is for others to have an input as well (including the patient support groups, the Defence Science and Technology Organisation, CSIRO, NICTA [our Information Communications Technology Research Centre of Excellence], the Australian Nuclear Science and Technology Organisation, Australian Research Council (ARC) and National Health and Medical Research Council (NHMRC), the hospital system and the state and federal governments). There must be discussions to ensure that translational research proposals really meet the needs of patients and hospitals, and can integrate with our nascent Australian biotechnology, IT and pharmaceutical industries. This will be one role that requires coordination by an Implementation Committee, to progress these recommendations and involve state and federal government officials as well as representatives from the community and the science sector.

We believe that the single most important point is the most general one: if we fail to become involved, at the highest level intellectually and clinically, in the ‘brain project’, we will opt out of a world research program at the most exciting time in this seminal field. The consequences will include losing some of our best and brightest researchers, and the opportunity to implement aspects of knowledge of the brain that are of great importance for our community, our economy and our citizens with brain disorders.

© 2017 Australian Academy of Science

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