Section 4

Citations

Citation 2000 - On the award of a University Chair to Prof. Maxwell BENNETT

Over the period from 1962 to the present time, Max Bennett has publish 250 research papers on the formation and function of synapses in the nervous system, and also four monographs on neuroscience subjects, including the history and philosophy of neuroscience. A fifth monograph is nearing completion. As a background to a brief description of Max Bennett's contributions to neuroscience, it should be pointed out that at the time Max Bennett began his research career, it was believed that in the peripheral nervous system only two substances (acetylcholine and noradrenaline) mediated all transmission between nerve cells, or between nerves and muscle.

In 1963, Max Bennett used electrophysiological techniques to show unequivocally for the first time that this classical paradigm was not correct. Both inhibitory and excitatory junctions between nerves and smooth muscle cells were shown to exist in which transmission was mediated by what have become known as non-adrenergic, non-cholinergic (NANC) transmitters. In the succeeding 37 years since this discovery, identification of these NANC transmitters has been a major task of neuropharmacology, and many new transmitters have been isolated, including neuropeptides, nitric oxide and purines. These discoveries have had a profound impact on our understanding of the way in which the nervous sytem controls the cardiovascular, gastrointestinal and urogenital systems as well as on the clinical treatment of disorders of these systems. Apart from the first demonstration of NANC transmitters, Max Bennett has pioneered efforts to understand the structure and functions of the connections between autonomic nerves and smooth muscle (autonomic neuroeffector synapses). He first showed how the electrical signs of transmission at NANC synapses is propagated through the electrical couplings of the smooth muscle cells. He then went on to show that NANC transmitters gives rise to an action potential in the muscle effectors that is due solely to the influx of calcium ions; this was the first naturally occurring calcium action potential ever described. More recently he has introduced techniques for recording, for the first time, the electrical signs of transmission from single sympathetic and parasympathetic variscosities and boutons that possess a single site for the release of these NANC transmitters. This has shown that there is considerable heterogeneity in the capacity of the different variscosities to secrete transmitter. In addition, Max Bennett and his colleagues have ascertained the distribution of molecules that control the secretion of NANC transmitters at these varicosities as well as the influx of calcium ions into them that triggers transmitter secretion. Finally, the way in which the molecular components that constitute a functional NANC receptor for the transmitter are assembled has also been determined.

Thus, these discoveries have allowed the structure and function of the presynaptic and postsynaptic components of the autonomic neuroeffector junction to be defined at the molecular level for the first time. Max Bennett has also made major discoveries on the molecular mechanisms governing the formation of synapses in early development and the maintenance of synapses in adulthood.These discoveries, which were largely carried out during the period from 1972 to 1992, incl ude (l) the discovery that during development the ingrowing nerve terminals induce the synthesis of specific molecules at specific sites on the surface of the target striated muscle cell, and (2) the demonstration that, in the event of subseqent damage to the nerve, these molecules then guide the formation of new synapses following regrowth of the nerve back into the muscle. During this period Max Bennett and his colleagues also discovered that the survival of central mammalian neurons depends upon factors supplied by the cells on which they normally form synapses.

Max Bennett's international acknowledgment as a scholar of exceptional distinction is clearly demonstrated in many ways. First, in 1999 he was awarded the Burnet Medal of the Australian Academy of Science, the leading prize in the biological and medical sciences in Australia . This was the first time that the award has been made to a researcher working in a University or Medical Researh Institute in NSW in the 30 year history of this medal.

Previously, in 1995 he was awarded the Ramaciotti Medal for excellence in biomedical research, the highest award of the Ramaciotti Foundation. Max Bennett has also received several leading awards for research excellence from the National Heart Foundation, including in 1996 the Goddard Research Award and in two successive years (2000 & 2001) the Almgren Research Award. Recently, in 2001, he was awarded the Distinguish Achievement Medallion of the Australian Neuroscience Society, the second time this Medal has been awarded for research in the 20 year history of the Society. Max Bennett was elected as a Fellow of the Australian Academy of Sciences in 1981, the first member of the Faculty of Medicine at the University of Sydney to receive this distinction. In 1982 he was appointed to a Personal Chair in the University of Sydney , becoming only the second person to receive this distinction (the first being Lord Robert May). In 2000 he was appointed to one of the first two University Chairs to be established at the University of Sydney for 'scholars recognized internationally as being of exceptional distinction'.

In 1981 the Commonwealth Government established the first Commonwealth Special Research Centres, and Max Bennett was awarded the largest grant of that first round to establish such a Centre of Excellence at the University of Sydney , which continued until 1990. Subsequently, Max Bennett has received grants totaling $4.85 million from the NHMRC, ARC and the National Heart Foundation to this time. Further evidence of Max Bennett's great distinction is that in 1996 he was invited to present the opening Plenary Lecture at the World Congress of Neurosciences in Kyoto , and in 1993 was invited by members of the Nobel Committee to Chair and present a lecture in a Symposium on the Synapse, in Stockholm . He has also been the Plenary Lecturer at Annual Meetings of the Australian Physiological and Pharmacological Socety (in 1980) and of the Australian Neuroscience Society (in 1982) and recently gave the Cade Anniversary Lecture at the Mental Health Institute of Victoria (in 1999). In addition, Max Bennett has been a editor of several major international journals during his career, and currently is the Review Editor of Autonomic Neuroscience, the Associate Editor of Progress in Neurobiology, and the Australasian Editor for Progress in Neurobiology.

Apart from his direct contributions to research in neuroscience, Max Bennett has demonstrated great leadership in the national and international scientific community. Within Australia, he chaired the Foundation Committee from (1984-1986) that led to the establishment of the Federation of Australian Scientific and Technological Societies (FASTS), which has become the main lobby group for the support of science and technology in Australia.

Secondly, Max Bennett was the Chair of the Foundation Committee (from 1986-1988) that led to the establishment of the Australian Societies for Experimental Biology, responsible for the 1988 Centenary of Medicine and Biology in Australia. Max Bennett also chaired the Foundation Committee (from 1994-1996) that led to the establishment of the International Society for Autonomic Neuroscience, was the Vice-President of this Society from 1996 to July 2000, and then in July 2000 was elected as the President of this Society, at the Congress of the Society held in London.

Citation 2001 - On receiving a 'Tall Poppy' award for Research Excellence: Contribution of Prof. Maxwell BENNETT to Discoveries in Autonomic Neuromuscular Transmission

When Max Bennett began his research career it was believed that in the peripheral nervous system only two substances (acetylcholine and noradrenaline) mediated all transmission between nerve cells, or between nerves and muscle. In late 1962, Max Bennett used electrophysiological techniques together with appropriate blocking drugs to show unequivocally for the first time that this classical paradigm was not correct (1, 2). Both inhibitory and excitatory junctions between nerves and smooth muscle cells were shown to exist in which transmission was mediated by what have become known as non-adrenergic, non-cholinergic (NANC) transmitters. In the succeeding 40 years since this discovery, identification of these NANC transmitters has been a major task of neuropharmacology, and many new transmitters have been isolated, including neuropeptides, nitric oxide and purines. These discoveries have had a profound impact on our understanding of the way in which nerves control the cardiovascular, gastrointestinal and urogenital systems as well as on the clinical treatment of disorders of these systems (see Ch.7 in 3).

Following his first demonstration of NANC transmitters, Max Bennett pioneered efforts to understand the structure and functions of the connections between autonomic nerves and smooth muscle (autonomic neuroeffector synapses), especially at synapses using NANC transmitters. He first showed how the electrical signs of transmission at NANC synapses is propagated through the electrical couplings of the smooth muscle cells, a mechanism that is necessary for NANC transmitters to control blood vessels and allows the NANC synapses to initiate action potentials in the muscles (4, 5, 6). He then went on to establish that these action potential in the muscle effectors are due solely to the influx of calcium ions (7). This was the first naturally occurring calcium action potential ever described in either the vertebrate or invertebrate nervous system and provided the basis for development of a most important groupof drugs involved in controlling hypertension through blocking calcium channels in vascular smooth muscle cells(see Ch.8 in 3).

More recently Max Bennett has introduced techniques for recording, for the first time, the electrical signs of transmission at single NANC synapses or varicosities as well as determining the influx of calcium ions into these varicosities necessary for them to secrete NANC transmitters (8). This has shown that there is considerable heterogeneity in the capacity of the different variscosities to secrete transmitter and that this is likely to be due to heterogeneity in the type and distribution of NANC receptor molecules on the varicosities that determinetransmitter release (9). Finally, and most recently, Max Bennett has shown that NANC receptor molecules on the muscle cell are located in a discrete array opposite each varicosity (10), and very surprisingly that these receptors are internalized into the muscle cells on binding NANC transmitter released from the overlying varicosity (ll).This work raises the possibility of transiently blocking transmission at NANC synapses in various relevant disease states by modulating the internalization rate of the NANC receptor molecules.

References

I. Bennett, M. R. (1965) A Study of Transmission for Autonomic Nerves to Smooth Muscle Thesis for the Degree of MSc, University of Melbourne .

2. Bennett, M.R., Burnstock, G. & Holman , M.E. (1966). Transmission from intramural inhibitory nerves to the smooth muscle of the guinea-pig taenia coli. 1.Physiol. (Lond.) 182: 541-558.

3. Bennett, M.R (2001) History of the Synapse Harwood Academic Publishers, London

4. Bennett, M.R. (1967) The effect of intracellular current pulses in smooth muscle cells of the guinea-pig vas deferens at rest and during transmission. 1. Gen. Physiol. 50: 2459­2475.

5. Bennett, M.R & Burnstock, G. (1968) Electrophysiology of the innervation of intestinal smooth muscle. Handbook of Physiology. Alimentary Canal IV. Ch. 84 pp. 1709-1732.

6. Bennett, M.R (1972). Autonomic Neuromuscular Transmission. Monograph of the Physiological Society No. 30, Cambridge University Press.

7. Bennett, M.R. (1967). The effect of cations on the electrical properties of the smooth muscle cells of the guinea-pig vas deferens. 1. Physiol. (Lond.) 190: 465-479.

8. Brain, K.L. & Bennett, M.R (1997). Calcium in sympathetic varicosities of mouse vas deferens during facilitation, augmentation and autoinhibition. 1. Physiol. (Lond.) 502: 521-536.

9. O'Connor, S.c. , Brain, K.L. & Bennett, M.R (1999) Individual sympathetic varicosities possess different sensitivities to a2 and P2 receptor agonists and antagonists in mouse vas deferens. Br. 1. Pharm. 128: 1739-1753.

10. Hansen, M.A., Balcar, V.J., Barden, 1.A. & Bennett, M.R (1998).

The distribution of single P2xl -receptor clusters on smooth muscle cells in relation to nerve varicosities in the rat urinary bladder. 1. Neurocytol. 27: 529-539.

11. Dutton, 1.1., Poronnik, P., Li, G.H., Holding, c.A., Worthington, RA., Vandenberg, R.J., Cook, DJ., Barden, 1.A. & Bennett, M.R (2000) P2Xl receptor membrane redistribution and down-regulation visualized by using receptor-coupled green fluorescent protein chimeras. Neuropharmacology 39: 2054-2066.

Citation 2002- On Prof. Maxwell BENNETT receiving the Academia Ophthalmologica Internationalis A ward

Professor Maxwell Bennett holds the first University Chair (2000) to be appointed in the University of Sydney for 'research recognized internationally of exceptional distinction' on the formation and function of synapses, especially those of the autonomic nervous system. For this work he has received the Ramaciotti Medal as well as the Burnet Medal of the Australian Academy of Sciences, the leading award in biology and medicine in Australia . In 2001 he was made an Officer in the Order of Australia for 'contributions to neuroscience' and was awarded

the Distinguished Achievement Medallion of the Australian Neuroscience Society, only the second person to receive this distinction for research. Max has been President of the Australian Neuroscience Society and is at present President of the International Society for Autonomic Neuroscience. His invited lectures include an Opening Plenary Lecture at the World Congress of Neuroscience in Kyoto and the Burnet Lecture of the Australian Academy of Sciences to which he was elected in 1981. In 1982 he was awarded the largest personal grant in Australia in the first Research Centres of Excellence program, later called Special Research Centres. Since that time he has been awarded on average $0.5 million per year in peer reviewed grants. Besides research Max has an interest in founding societies for the benefit of science and medicine and was instrumental in founding the Federation of Australian Scientific and Technological Societies (FASTS) in 1984. He is the author of five books on the history and philosophy of neuroscience as well as of monographs, and has personally written over 280 research papers on the formation and function of synapses.

Citation 2008 - On completing 40 years of research at the University of Sydney

Summary

Maxwell Bennett AO

Maxwell Bennett is Professor of Neuroscience in the University of Sydney and holds one of the first two University Chairs for research ‘recognized internationally to be of exceptional distinction’. He graduated in Electrical Engineering and did his doctoral research in Zoology at Melbourne University before turning to the brain sciences and being appointed to the second Personal Chair at Sydney University, after Lord May.
His books and papers are concerned with research on the formation and function of synaptic connections between nerve cells, on the history and philosophy of the brain sciences, and on science policy. His most recent books are The Idea of Consciousness, History of the Synapse and Philosophical Foundations of Neuroscience, Neuroscience and Philosophy as well as History of Cognitive Neuroscience. Amongst the organizations he has initiated to promote science and brain research are the Federation of Australian Scientific and Technological Societies, the International Society for Autonomic Neuroscience, Brain and Mind/Asia-Pacific and recently the Brain and Mind Research Institute (BMRI).

For services to the brain sciences and mental health through research, the founding of new institutes and organizations to further this research and as the international authority on the history and philosophy of the brain sciences.

1. Contributions to neuroscience

For sixty years it was thought that nerve terminals release only two substances (noradrenaline and acetylcholine) that control the cells on which they make connections. Bennett showed that there are at least two other substances released and now over thirty have been identified.  One of these, ATP, has been shown to play a major role in the generation of pain following nerve injury as well as in the immune systems control of inflammation. This has resulted in contemporary pharmacology having as a main aim the blocking of ATP so as to ameliorate pain and cell death. Bennett also discovered that nerve terminals reform connections on other cells after a nerve injury at sites which have specialized molecules on their surface for triggering the terminals to stop growing and form a synapse. The identification of these synapse formation molecules is a main task of molecular neuroscientists, with several of the molecules now recognized. This holds out great hope for reconstructive nerve regeneration after injury. Bennett’s research also revealed that there are silent synapses, in which nerve terminals are physically present but do not release transmitters. This has had profound impact on research concerned with changes in the brain responsible for learning and memory. The search for the mechanisms which activate silent synapses is a major area of contemporary investigations on the synapse. As a consequence of this research on nerve terminals the University of Sydney conferred on Bennett in 2001 its first University Chair, for ‘research recognized internationally as of exceptional distinction’. In addition, in 2001 he received the Distinguished Achievement Medal of the Australian Neuroscience Society, only the second time it had been awarded in the 25 year-old history of the Society. Later, in 2001, he was elected President of the International Society for Autonomic Neuroscience, the main international organization concerned with how the brain controls the internal organs such as the heart and blood vessels and of what goes awry in the brain under conditions of extreme stress and in cardiovascular diseases.

2. Contributions to the history and philosophy of the brain and mind sciences

Bennett is the leading neuroscientist on the history and philosophy of brain and mind research. The main theme of his philosophical work is that the brain sciences have distorted the use of language in attributing our psychological capacities as in thinking, remembering, perceiving etc to the brain rather than to the person whose brain it is; the brain being necessary for us to express these abilities, but it is we who express them. This has profound implications for how we view ourselves. In his historical work Bennett has followed the evolution of our ideas concerning the functioning of the different components of the brain and their organization from the time of Aristotle to the present. He has shown how fundamental ideas arise in this area through a combination of research, prejudice and irrationality and of how strong hypotheses concerning brain function are often abandoned for extended periods of time in favor of less logical hypotheses. Bennett’s most recent works include History of the Synapse (2000);  Philosophical Foundations of Neuroscience (2003; with P.Hacker); Neuroscience and Philosophy: Brain, Mind and Language (with D.Dennett, J.Searle and P. Hacker; 2006); and History of Cognitive Neuroscience (2008, with P. Hacker) . Recognition of his stature in this area was afforded in Christmas 2005 when he was invited by the American Philosophical Association to give a plenary presentation at their annual meeting in New York, the first neuroscientist to be so invited.

3. Contributions to the founding of new organizations to promote brain and mind research
Bennett has a tremendous commitment to the amelioration of diseases of the brain and mind. To this end he established the major research/clinical facility in Australia for the treatment/research of those suffering from these diseases, ‘The Brain and Mind Research Institute’ at Sydney University. The first stage of this was opened by the Governor of NSW (Professor Marie Bashir AC) in 2004, the second stage by the Prime Minister of Australian, the Honorable John Howard in June 2006 and the third stage by the Premier of NSW the Honorable Morris Iemma in February 2007. Raising over $ 50 million has allowed a complex of four buildings devoted to the amelioration of brain disease through the integrated work of basic brain sciences, clinical and translational research and youth mental health.
Bennett founded the organization  ‘Brain and Mind, Australia’ in 2002 which has been responsible for major symposia and workshops each year concerned with bringing together the best brain scientists and clinical psychiatrists. He has been responsible for organizing the thirty-six University and Research Institutes that make up the Association of Pacific Rim Universities forming ‘Brain and Mind, Asia/Pacific’ in 2004-2005. The aim of this is to marshal the great research strengths of these Universities to ameliorate diseases of the brain and mind. His work on the Mental Health Council of Australia (2002-) and as a Director of the Australian Brain Foundation (2004-), of Neuroscience Australia (2002-2005) as well as of the Institute for Biomedical Research (2002-2006) and the International Brain Research Organization (1996-2002) has enabled him to make further contributions to assist those suffering from diseases of the brain and mind.

4. Contributions to the community through explaining the discoveries made in the brain sciences and their implications.
Bennett has felt a major responsibility to explain progress made in the brain sciences to the community as well as the ethical and philosophical issues which arise from this progress. He frequently makes invited presentations to, for example, gatherings of Supreme Court Judges (2004), senior business leaders (2004, 2005), church leaders (2004) and public forums involving dialogue with distinguished guests such as the Dali Lama (2002). In addition, Bennett is a frequent guest in the media, making presentations on questions concerning brain and mind research and its history, such as on John Cade (the discoverer of lithium for the treatment of bipolar manic/depression: 2004) and Sir John Eccles (the Australian Nobel Prize winning brain scientist and theorist on the relation between brain & mind: 2002). In addition Bennett has been chosen to assist in many Australian Government task forces to advise Ministers of Health, Education and Science on how to best optimize the nations research capacity in the brain and mind sciences and use this forthe alleviation of suffering of our fellow citizens.

GRATEFUL ACKNOWLEDGEMENTS

Contributions to the history and philosophy of neuroscience on brain and mind as well as the establishment of new organizations to support research aimed at ameliorating diseases of brain and mind could not have been achieved without collaboration, support and guidance from the following:

1. Brain and Mind Research Institute

(a) Establishment of the Institute and its Foundation
Prof Gavin Brown AO
Tom Cropper
David Gonski AC
Bruce Hawker
Michael Hawker
John Hooke OBE
Robert Johnston AC
Ken Parker (deceased)
Daniel Petre AO
Oliver Richter AO
Kerry Stokes AO
Ryan Stokes
Fred Street AM
Warren Hogan

(b) Support & advise on establishing the Institute
Prof Steven Leeder AO
Prof James McLeod AO
Hon Kim Santow AO
Hon. James Spigelman AC

(c) Colleagues in the Institute
Prof Ian Hickie AM
Prof John Pollard AO

2. History and Philosophy of Neuroscience

Dr Peter Hacker
Prof Noel Hush AO
Sir Anthony Kenny
Prof Denis Noble
Prof Mandyam Srinivasan

3. New Organizations to promote science and brain research

1. Federation of Australian Scientific and Technological Societies

Prof Robert Crompton AM
Prof Robert Porter AC
Prof Steven Redman
Prof Harold Warnock (deceased)

1. International Society for Autonomic Neuroscience

Prof James Angus
Prof Roger Dampney
Prof John Furness
Prof Paul Korner
Prof Lennart Stjarne

1. Brain and Mind, Asia/Pacific

Prof Shih Choon Fong
Prof Barry Halliwell
Prof Gary Housley