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Sir John Eccles' exceptional legacy

The University's new $49.8 million Research Support Facility will future-proof Otago's status as a leading scientific institution. The 3,936m2, five-storey building features state-of-the-art technologies to underpin important health and biomedical research, and meets stringent animal welfare regulations and health and safety requirements. Soon to be opened, the facility is named after Sir John Eccles, the Nobel Prize winning scientist whose research undertaken during his years at Otago continues to have a profound effect on neuroscience today.

Nobel Prize winner Sir John (Jack) Eccles was head of Otago's Department of Physiology when he made the breakthrough discovery that ultimately led to his prestigious award.

In a triumph for science, Professor Eccles and his Otago team disproved an early theory about brain function, thereby confirming an alternative theory that became a fundamental concept in brain research.

Eccles effectively established that the way in which nerve cells in the brain transmit information between them – synaptic transmission – is a chemical process rather than an electrical one. The discovery is still the current basis for understanding brain function both in health and in the treatment of mental illness and neurological disease.

Eccles came to Otago following a Rhodes Scholarship to Oxford, earned in his native Australia, where he had graduated in medicine and surgery in 1925. At Oxford, he studied Physiology and Biochemistry and launched his stellar research career under the supervision of early neuroscientist Sir Charles Sherrington, who in 1932 won the Nobel Prize in Physiology or Medicine for discoveries about how neurons function.

Working at Sherrington's laboratory led Eccles into a controversial scientific debate that set him up in opposition to another research giant, pharmacologist and physiologist Sir Henry Dale. Dale and Otto Loewi won the Nobel Prize in Physiology or Medicine in 1936 for work establishing chemical synaptic transmission in the peripheral nervous system, and went on to speculate that the central nervous system might also use neurochemical transmission.

Eccles was prominent among other neurophysiologists who supported the alternative view that the speed of transmission at synapses where neurons communicate in the brain was too rapid to be a chemical process and was more likely to be electrical.

With Sherrington's retirement and the imminent approach of war in Europe, Eccles decided to leave Oxford for a post at Sydney Hospital with the debate still unresolved. His new position allowed him to continue his research, but the outbreak of war severely limited its scope and in 1944 he accepted a Chair of Physiology at the University of Otago.

Here he set up a talented multidisciplinary research team, including Lawrence Brock, who had graduated from Otago in Chemistry and Medicine, and Jack Coombs, an electronics engineer from the Department of Physics.

Between them, they developed solutions to the problems Eccles and others had faced for years in trying to solve the outstanding chemical-electrical controversy – how to successfully measure and record intracellular voltage changes in the spinal cord.

Coombs, described by Eccles as a shy genius, devised a highly sensitive electronic stimulating and recording unit (ESRU) that outclassed anything found in neurophysiology laboratories elsewhere and became known as the world's best general research instrument for electrophysiology for many years.

Brock succeeded in inserting a fine glass micro-electrode less than a micrometre wide into a single nerve cell so it could pick up the changes in the action potential to feed to Coombs' ESRU.

The pressures of a heavy teaching load during the day often saw researchers continuing late into the night, as was the case in August 1951 when one of the key experiments – on an anaesthetised cat – was temporarily put on hold for Brock to deliver a baby girl for Coombs' wife, while Eccles cared for the cat.

The experiment resumed and continued into the early morning hours, with the result becoming a pivotal moment in the history of neuroscience. Eccles' team finally proved that their theories that synapse transmissions in the central nervous system were electrical were wrong. They were chemical, as Dale had suggested.

Eccles was swift to accept the science. Disproving his own theory was as important as supporting Dale's, which fitted with discussions he had had with visiting Philosophy Professor Karl Popper.

Popper suggested that the strength of a scientific hypothesis depended not just on it being clearly formulated and checkable by experiment, but also on the failure of rigorous investigation to falsify it rather than on evidence that apparently supported it.

Eccles took heart in following the deductive process, which enabled the development of daring hypotheses as long as they could be rigorously tested until they either failed, or added weight to alternative ideas.

Following the breakthrough, Eccles did a lecture tour of the UK, publishing his findings in The Neurophysiological Basis of Mind: The Principles of Neurophysiology, one of the most influential texts in neuroscience in the 20th century, representing the beginning of a new era in neuroscience and the developing discipline of neuropharmacology.

In 1953 he took up the founding Chair of Physiology at John Curtin School of Medical Research in Canberra, where he could continue research without the pressure of teaching.

In 1963 Eccles was awarded the Nobel Prize in Physiology or Medicine with A.L. Hodgkin and A.F. Huxley, for fundamental contributions to the biophysical properties of synaptic transmission in the brain.

He went on to research in Chicago and Buffalo before retiring to Switzerland, where he continued to be involved in debates and wrote extensively. His last book, How the Self Controls its Brain, was published in 1994, just three years before his death at 94.

At Otago, Eccles left a legacy of daring experimentation, supported the founding of the Portobello Marine Research Laboratories, and mentored students and faculty members who went on to highly successful careers.

Internationally, Eccles is regarded as one of the leading neuroscientists of last century and his work continues to influence research, says Physiology Associate Professor Phil Sheard.

“Everything that makes us who we are, every mechanism we use to sense our world, to think about it, and to interact with it is dependent upon chemical signals between nerve cells. When these signals go awry we recognise major neurological or psychiatric problems, and many of these problems are fixable because we know how to modify the chemical signals that Eccles discovered.”

NIGEL ZEGA

John C. Eccles, Professor of Physiology, Medical School, University of Otago, 1949. Prime Minister's Department photograph, Box-184-128, Hocken Collections, Uare Taoka o Hākena, University of Otago.

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