The 2018 Oration
The 2017 Oration
Transitions in Cancer Research
Cancers have been recognised as lethal diseases since antiquity, but systematic studies that advance our understanding, prevention, diagnosis, and treatment of these diseases have been performed for only about a century.
For the first half of that time, the methods available for cancer research were not well suited to comprehending diseases that later proved to be based on alterations of genomes, mostly somatic mutations and rearrangements. The situation improved when new research tools were developed for studying cancer-causing viruses quantitatively; for establishing the mutational activity of chemical and physical causes of cancer; for isolating and manipulating genes instrumental in carcinogenesis; and for modelling the development of various types of cancer in laboratory mice.
With the recent advent of rapid DNA sequencing, it became possible to analyse the damaged genomes of human cancers in remarkable detail, promoting more rigorous diagnosis, new forms of epidemiology, and rational therapies. The novel treatments include drugs that target miscreant proteins and immunotherapies that encourage a patient’s immune cells to attack cancer cells. Still newer methods for characterizing single cells, not just collections of tumour cells, are now promoting a deeper understanding of tumour initiation, evolution, prognosis, heterogeneity, metastasis, and resistance to therapies.
"I will discuss some of these features of the episodic history and the promising landscape of cancer research, with references to my own career in this field and the accompanying changes in social and medical practices."
Dr Harold Varmus
The 2015 Oration
Science and Technology: New Frontiers for Helping People with Mental Illness
Mental illnesses are amongst the most common, disabling, and costly disorders in all of medicine. In contrast to most medical disorders, mental illnesses (including depression, anxiety disorders, schizophrenia, and bipolar disorder) usually begin before age 25. This early onset combined with low rates of treatment too often incurs disability and high medical and social costs. One recent report estimated the annual cost of mental illness in Australia at over $28B per year, 2.2% of the nation’s GDP. In addition to the disability and costs, these disorders are often fatal. In Australia, suicide has increased to the highest rate in 13 years, with the recent report of 2,864 deaths/year or nearly one every 3 hours. Fortunately, science and technology offer hope for reducing the high morbidity and mortality of these disorders.
The revolutions in genomics and brain imaging have begun to reveal the fundamental biology of psychosis as well as mood and anxiety disorders, changing our perspective on these illnesses from exclusively behavioral problems to disorders of specific brain circuits. Meanwhile new sensors and software that have revolutionized so many aspects of our lives have begun to offer better ways of measuring behavior, promising powerful tools for detecting early signs of psychosis or depression. Modern scientific and information technologies not only are suggesting more precise diagnostic boundaries that may help people get the right treatment at the right time, they are creating new approaches to treatment that may improve outcomes and prevent suicide.
During his tenure, Dr. Insel focused on the genetics and neurobiology of mental disorders as well as transforming approaches to diagnosis and treatment. Prior to serving as NIMH Director, Dr. Insel was Professor of Psychiatry at Emory University where he was founding director of the Center for Behavioral Neuroscience and director of the Yerkes Regional Primate Center in Atlanta.
Dr. Insel’s research has examined the neural basis of complex social behaviors, including maternal care and attachment. A member of the National Academy of Medicine, he has received numerous national and international awards and served in several leadership roles at NIH, including as founding co-leader of both the NIH BRAIN Initiative and the NIH Neuroscience Blueprint and interim Director of the National Center for Accelerating Translational Sciences (NCATS).
Controlling how cells reproduce
Sir Paul Nurse
As President of the Royal Society, Sir Paul leads the longest surviving scientific body in the world (founded November 1660), which has included as past presidents Sir Isaac Newton, Sir Joseph Banks, Sir Ernest Rutherford and Sir Howard Florey. In this capacity, Sir Paul is responsible for providing high-quality, independent advice to the UK Government on science and science policy.
As Director of the Francis Crick Institute, which will open in 2015, Sir Paul oversees the development of the largest medical research facility in Europe that will employ over 1,400 scientists.
All living organisms are made of cells, and their reproduction from one to two underpins the growth development and reproduction of all life. The molecular mechanisms that control the progression through the cell reproductive process called the cell cycle, is conserved in all life, from the simplest single cell organisms such as yeast through to human beings. In giving the Graeme Clark Oration, Controlling how cells reproduce, Sir Paul will describe the experiments from his laboratory which led to the identification of that mechanism and that showed it was conserved throughout the tree of life.
The mechanisms that Sir Paul will discuss contribute to our understanding of diseases, in particular cancer.
Paul Nurse is a geneticist and cell biologist who has worked on how the eukaryotic cell cycle is controlled and how cell shape and cell dimensions are determined. His major work has been on the cyclin dependent protein kinases and how they regulate cell reproduction. He is President of the Royal Society and Director of the Francis Crick Institute in London and has served as Chief Executive of Cancer Research UK and President of Rockefeller University. He shared the 2001 Nobel Prize in Physiology or Medicine and has received the Albert Lasker Award and the Royal Society's Royal and Copley Medals. He was knighted in 1999 and received the Legion d'honneur in 2003.
The Next Technology Wave: Biologically Inspired Engineering
Donald E. Ingber, M.D., Ph.D.
Founding Director, Wyss Institute for Biologically Inspired Engineering at Harvard University
Judah Folkman Professor of Vascular Biology, Harvard Medical School & Boston Children’s Hospital
Professor of Bioengineering, Harvard School of Engineering & Applied Sciences
The Wyss Institute for Biologically Inspired Engineering at Harvard University that I lead was founded in 2009 to develop new engineering innovations by emulating the way nature builds. Over the past 5 years, the Institute has pioneered a new model for innovation, trans-disciplinary collaboration and technology translation, while developing an exciting pipeline of new bioinspired technologies, including two that have entered human clinical trials. A few examples include therapeutic cancer vaccines that act as artificial lymph nodes; nanotherapeutics that target to vascular occlusion sites like artificial platelets; self-assembling DNA-based nanorobots that can be programmed to travel to cancer sites and kill tumor cells; and a microfluidic device that cleanses blood of pathogens and toxins in septic patients like the human spleen.
In addition to summarizing these developments, in this oration I will highlight recent advances my team has made in the engineering of microfluidic “Organs-on-Chips”, microchips lined by living human cells created with microfabrication techniques that recapitulate organ-level structure and functions as a way to replace animal testing for drug development and mechanistic discovery. I will review recent advances we have made in the engineering of multiple organ chips, including lung, gut, kidney, liver and bone marrow chips.
I will also describe our ongoing efforts to integrate these organ chips into a “human body-on-chips”, and to engineer an automated instrument for real-time analysis of cellular responses to pharmaceuticals, chemicals, and toxins.
This new bioinspired technology wave represents a major paradigm shift in medicine, and the novel organizational structure of the Institute offers an entirely new way to translate our discoveries into breakthrough products in the academic setting.
Dr Donald Ingber is the Founding Director of the Wyss Institute for Biologically Inspired engineering at Harvard University. He also holds the positions of the Judah Folkman Professor of Vascular Biology, Harvard Medical School & Boston Children’s Hospital and Professor of Bioengineering, Harvard School of Engineering & Applied Sciences.
He received his B.A., M.A., M.Phil., M.D. and Ph.D. from Yale University. Dr. Ingber is a founder of the emerging field of biologically inspired engineering, and at the Wyss Institute, he oversees a multifaceted effort to identify the mechanisms that living organisms use to self-assemble from molecules and cells, and to apply these design principles to develop advanced materials and devices for healthcare and to improve sustainability.
He also leads the Biomimetic Microsystems platform in which microfabrication techniques from the computer industry are used to build functional circuits with living cells as components. His most recent innovation is a technology for building tiny, complex, three-dimensional models of living human organs, or “Organs on Chips”, that mimic complicated human functions as a way to replace traditional animal-based methods for testing of drugs and establishment of human disease models.
In addition, Dr. Ingber has made major contributions to mechanobiology, tissue engineering, tumor angiogenesis, systems biology, and nanobiotechnology. He was the first to recognize that tensegrity architecture is a fundamental principle that governs how living cells are structured to respond biochemically to mechanical forces, and to demonstrate that integrin receptors mediate cellular mechanotransduction.
Dr. Ingber has authored more than 375 publications and 85 patents, and has received numerous honours including the Holst Medal, Pritzker Award from the Biomedical Engineering Society, Rous-Whipple Award from the American Society for Investigative Pathology, Lifetime Achievement Award from the Society of In Vitro Biology, and the Department of Defense Breast Cancer Innovator Award. He also serves on the Board of Directors of the National Space Biomedical Research Institute, and is a member of both the American Institute for Medical and Biological Engineering, and the Institute of Medicine of the National Academies.
Global Health, Economic Growth and the End of Absolute Poverty: hopeful evidence and hard challenges
The 2013 oration was an extraordinary success with over 1500 people attending. Geoff Lamb explained that through investments in health and an increase in economic growth, a real impact has been made on global absolute poverty.
The oration reviewed the extraordinary successes of the past half century in reducing mortality and disease. It will show how investments in health have been critical for economic growth and the reduction of global poverty – and helped bring the goal of an end to absolute global poverty within generational sight. But in retrospect the huge basic health advances of recent decades may have been the easy part.
For example, big investments in routine vaccination and cleaner water may already have delivered up most of their dividends, and meantime we may face a “long contraction” in public finances that will make it much harder to fund future investments. What needs to be done to ensure the next transformation in global health, and make the end of absolute poverty attainable?
Geoffrey Lamb is the Gates Foundation’s President, Global Policy and Advocacy. He leads the foundation’s international policy and advocacy team, and its engagement with governments and international institutions. Lamb was previously Managing Director, Public Policy and a Senior Fellow in the foundation's Global Development Program.
Before joining the foundation in 2006, Lamb held several senior positions at the World Bank, most recently as vice president of Concessional Finance and Global Partnerships. In that capacity, he chaired a series of international negotiations through which governments provided the largest increase in more than two decades of World Bank funding for the world's poorest countries, and subsequently agreed on the financial framework to forgive the multilateral debt of 40 countries.
An Irish citizen, Lamb was born in South Africa and educated in South Africa and the United Kingdom, where he was a fellow and deputy director of the Institute of Development Studies at the University of Sussex. He was a member of the board of the Global Fund to Fight AIDS, Tuberculosis and Malaria from its founding until 2006, and has been a board member of the International Aids Vaccine Initiative since 2000, and its chairman 2003-2008. He has served as chairman of the international negotiations for the replenishment of the African Development Bank’s concessional arm, the African Development Fund, in 2009/10.
Professor Dame Linda Partridge
The fourth Oration, Forever Young?, was delivered by Professor Dame Linda Partridge, Weldon Professor of Biometry and Director of the Institute of Health Ageing, University College London.
Professor Partridge discussed the history of research in ageing and the recent discussions regarding the role of genetics in ageing. The impact of drugs which replicate genetic alterations in prolonging lifespan was also discussed. She then turned her attention to the role of dietary restriction in improved lifespan.
The Oration was attended by over 1,000 people. The Governor of Victoria, the Honourable Alex Chernov, AC QC, introduced Professor Partridge. Laureate Professor Emeritus Graeme Clark thanked Professor Partridge at the conclusion of her oration and presented her with the Oration memento.
The Oration Dinner was the biggest ever, with 410 guests. Dr Norman Swan, host of the ABC’s Health Report was the MC. A highlight of the dinner was the screening of a video prepared for the event, featuring members of the public with their thoughts on the issue of ageing. It also featured commentary from well-known forecaster, Mr Phil Ruthven, on the economic impact of ageing. The highlight was an interview with Mrs Muriel Craddock, who was 100 years old in March 2012. Mrs Craddock was present at the dinner and warmly welcomed by the guests.
Some 35 secondary school students and their teachers attended the oration dinner as guests of several sponsors, including VESKI, VLSCI and NICTA. Some students asked questions of Professor Partridge during the Q&A that followed the serving of the main course.
Professor Partridge delivered an outstanding and memorable Graeme Clark Oration.
The Computational Brain
Professor Terrence J Sejnowski
The 2011 Graeme Clark Oration, The Computational Brain, was delivered by Professor Terrence J Sejnowski. Professor Sejnowski is a pioneer in computational neuroscience and his goal is to understand the principles that link brain mechanisms to behaviour.
His research focused on the hippocampus, believed to play a major role in learning and memory, and the cerebral cortex, which holds our knowledge of the world and how to interact with it. His laboratory uses both experimental and modelling techniques to study the biophysical properties of synapses and neurons and the population dynamics of large networks of neurons. New computational models and new analytical tools have been developed to understand how the brain represents the world and how new representations are formed through learning algorithms for changing the synaptic strengths of connections between neurons. He has published over 300 scientific papers and 12 books, including The Computational Brain, with Patricia Churchland.
He received his PhD in physics from Princeton University and was a postdoctoral fellow at Harvard Medical School. He was on the faculty at the Johns Hopkins University he now holds the Francis Crick Chair at The Salk Institute for Biological Studies and is also a Professor of Biology at the University of California, San Diego, where he is co-director of the Institute for Neural Computation and co-director of the NSF Temporal Dynamics of Learning Center. He is the President of the Neural Information Processing Systems (NIPS) Foundation, which organises an annual conference attended by over 1000 researchers in machine learning and neural computation and is the founding editor-in-chief of Neural Computation published by the MIT Press.
An investigator with the Howard Hughes Medical Institute, he is also a fellow of the American Association for the Advancement of Science and the Institute of Electrical and Electronics Engineers. He has received many honors, including the Wright Prize for interdisciplinary research from Harvey Mudd College, the Neural Network Pioneer Award from the Institute of Electrical and Electronics Engineers and the Hebb Prize from the International Neural Network Society. He was elected to the Institute of Medicine in 2008 and to the Academy of Sciences in 2010.
The Oration, The Computational Brain, explored:
• the workings of the brain;
• whether we are any closer to building artificial brains;
• how our understanding of the brain is transforming ideas about learning and education and the role of social robots; and
• brain behaviour in disorders such as autism and schizophrenia.
Writing the Genetic Code
Dr J Craig Venter
Genomics pioneer, Dr J Craig Venter delivered the 2010 Graeme Clark oration to an audience of 2,000 people on 17 March, 2010. From Reading to Writing the Genetic Code surveyed the past 15 years’ effort to digitise biology and what is being referred to as the dawn of the new phase of biology, using digitized information to write new genetic code to code[?] for new biological systems and processes.
In introducing Dr Venter, the Governor of Victoria, Professor David de Kretser, AC, noted that the ability to read the genetic make up of an individual has profound implications for how medicine is practised and how the lives of people can be improved.
Dr Venter began his talk by describing how he came to be involved in the field of genomics. In 1987 his lab at the National Institutes of Health was researching neurotransmitter receptors and receptor biochemistry of different types and parts of the human physiology, using an automated DNA sequencer. Discussion of the human genome project at the time was seen as a big step in science and was the fascination that saw Dr Venter turn his attention to this project.
Dr Venter’s lab undertook some of the initial sequencing of the human genome to see if this was possible. His team found that while sequencing was possible, the interpretation of that sequence was extremely complicated. This led to the development of Expressed Sequence Tags (ESTs), the mechanism by which chromosomes could be interpreted. By 1991, only 337 genes had been sequenced, and this number had grown to almost 65 million by early 2010. The first haploid human genome (23 chromosomes) was sequenced in 2000 and the first diploid genome (46 chromosomes) was sequenced in 2007.
Dr Venter described how ESTs were then used to sequence sea water in the oceans to find new life forms through the J C Venter Institute’s Global Ocean Sampling Expedition. These expeditions have found an abundance of microbial life. When Dr Venter started his efforts to sequence the human genome, there were less than a million genes known to science. The ocean sampling expedition has now grown this figure to 20 million genes, and rising! Importantly, Dr Venter has placed the data from his sampling expeditions on the internet for everybody to use. Sampling in the air and the earth’s crust has also found an abundance of microbial and viral life.
Having described the sequencing, or writing, of the genetic code, Dr Venter then examined the next phase of the journey, constructing an artificial chromosome, or writing the genetic code. The process he described resembled an assembly line, only it is DNA that is being assembled! The automatic process goes straight from a computer to synthesize large pieces of DNA molecules without any human intervention. The process of constructing a living microbe involves the sequencing of a genome, synthesising it and transplanting it into a cellular environment in a living host. That is, computer software is placed into a cell via synthetic DNA, which strats producing new proteins created by this software and thereby creates a new cell. The writing of the genetic code is now complete.
Having a process by which DNA can be written much like computer code, Dr Venter discussed how this technology could be put to use to address one of the world’s most pressing problems, the growing demand for energy and the creation of greater levels of carbon dioxide. With global population forecast to grow to 9 billion by 2050, this is a pressing issue. Dr Venter’s solution is to design microalgae that produce fuels that can replace our reliance on conventional sources. The engineering challenge is to build facilities of a scale that can produce the synthetic replacement biofuels in very large quantities. ExxonMobil is funding Dr Venter and his team to determine if the process can be scaled up from the lab to an industrial plant.
Shortly after he delivered the Oration, Dr Venter announced on 20 May in the journal Science that he and his team had created the first “synthetic cell”, Mycoplasma mycoides JCVI-syn1.0, more commonly referred to since as Synthia. Dr Venter was at pains to stress that what he and his team had achieved was not the creation of life from scratch, but that they had transformed existing life into new life.
Dr Venter delivered a tour de force that will be talked about for some time. Who knows whether the promise of designed DNA will become a reality, and what challenges await it. But the 2010 Graeme Clark Oration certainly could not but inspire the imagination about the possibilities that the convergence of biology, computing and engineering is capable of delivering.
The Inaugural Graeme Clark Oration
Professor Graeme Clark
A Partnership in Research Leading to the Bionic Ear and Beyond
The ICT for Life Sciences Forum’s annual showcase event, the Graeme Clark Oration, was held at the University of Melbourne on Monday, 27th October, 2008.The Oration will become an annual event to honour the achievements of Professor Graeme Clark, A.O., who developed the first multi-channel cochlear implant in Melbourne in the mid 1970s, and which is seen as a very early example of the convergence of the physical and medical sciences in Australia.
The Oration commenced with the screening of a video message from the Governor of Victoria, Professor David de Kretser, AC, in which he congratulated Professor Clark on his breakthrough achievement, and commented on the prospects for further breakthroughs offered by the collaboration between the physical and life sciences.
The Dean of the Melbourne School of Engineering, Professor Iven Mareels, recounted the involvement of the Department of Electrical and Electronic Engineering in Professor Clark’s wonderful achievement.
The Victorian Government was represented by Mr Evan Thornley, Parliamentary Secretary to the Premier for Innovation. He cited the extraordinary determination shown by Professor Clark in developing the bionic ear, a truly transformative technology.
In his oration, “A Partnership in Research Leading to the Bionic Ear and Beyond”, Professor Clark delivered a history of the development of the bionic ear, and the partnership between people and disciplines necessary to achieve this. The journey started in 1967 when Professor Clark commenced his PhD at Sydney University, with, as he described it as “...a partnership of one”. His studies were completed in 1969, with the conclusion that “...if pure tone reproduction is not perfect, meaningful speech may still be perceived if speech can be analysed into its important components, and these used for electrical stimulation. More work is required to decide which signals are of greatest importance in speech perception”.
The opportunity to pursue this research came when he was appointed to the first chair in otolaryngology in Australia, created in 1969 at the University of Melbourne. Soon after his appointment, Professor Clark’s statement that implanting electrodes into the ear and stimulating the auditory nerve electrically would make it possible for totally deaf children to hear and speak like others drew criticism. Nevertheless, his appointment allowed Professor Clark to establish a laboratory and develop his team to answer some fundamental questions. His initial research concluded that the single-channel systems being investigated in the US and Europe at the time would not be able to reproduce the important speech frequencies from about 50 Hz up to 4,000 Hz and allow speech understanding to occur. These frequencies would need to be reproduced through multi-channel stimulation. Mathematical modelling and physiological studies determined that the electrodes needed to lie within the cochlea.
In 1974, the need to design and develop an implantable device led to a partnership with the Department of Electrical Engineering at the University of Melbourne, with the principal participation of David Dewhurst and Ian Forster. The generosity of a local TV station, Channel 10, in holding two telethons, and the support of other corporate organisations, allowed Professor Clark and his team to develop the most complex package of electronics yet implanted in a patient.
That moment arrived in 1978, when Professor Clark and Dr Brian Pyman performed the first operation, on 1 August, to implant a multi-channel cochlear implant: the patient was Rod Saunders.
In 1981, a grant from the Australian government helped a subsidiary of the pacemaker firm Telectronics, Cochlear Limited. By September 1982, Cochlear had developed a new implant and speech processor.
Having successfully demonstrated speech processing for adults, the next question became could children born deaf understand speech with electrical stimulation using the same strategies? The answer was to come following the cochlear device being implanted in the first two young children in 1985 and 1986. This resulted, in 1990, in a world trial for the US food and Drug Administration, which later announced that the 22-chanel cochlear implant was safe and effective in enabling deaf children from the ages of two through 17 years to understand speech both with and without lipreading.
Professor Clark ended his oration with a look to a future of near normal hearing for all that improved speech processing might deliver, made possible by advances in intelligent polymers.
Following Professor Clark’s delivery, Sophie Li, a bilateral cochlear implant recipient, delivered a personal and moving account of how the cochlear implant changed her life. Her story was a testament to the impact of Professor Clark’s achievement in creating the bionic ear, and this story is very likely replicated in each of the other 100,000 plus people, and growing, around the world that have received a bionic ear.
Afterwards, a private dinner was held for Professor Clark, which included many of the individuals who had been involved over the years in the partnership described in the oration. Special guests included the surviving daughters of Rod Saunders, Christine Zygmunt and Karen Saunders, Marjorie Dewhurst, widow of David Dewhurst, Brian Pyman, and Ari Fisher, a recipient of the cochlear implant.