Obituary: Sir John Eccles

Sir John Eccles was pre-eminent as a neurophysiologist whose life was devoted to unravelling the secrets of the central nervous system. To this task he brought a brilliant intellect, enormous energy and formidable stamina. He transformed our understanding of the detailed cellular interactions among nerve cells in the nervous system, though the task he set himself of understanding the human mind eluded him, as indeed it has many others.

He was born in Melbourne, Australia, in 1903. His father was a school teacher. Eccles read Medicine at Melbourne University and had a meteoric academic career gaining a first class degree and winning a Rhodes Scholarship to Oxford. Here he completed his academic training in Sir Charles Sherrington's Department of Physiology, adding an MA and a D Phil to his attainments, plus an Oar - a sporting trophy in the arcane game of chasing boats and gaining bumps. He also won the Gotch and Rolleston Prizes, a Research Fellowship at Exeter College, a Fellowship at Magdalen and a lectureship at Oxford University - all in the space of 12 years.

At Oxford, his lifelong preoccupation with the nervous system began to unfold. The most notable early result was a sequence of scientific papers on hind-limb withdrawal reflexes, published in 1930-31 with Sherrington. Eccles seems rather quickly to have decided that the connections between nerve cells held an important clue to the operation of the brain, and the synapse (a term coined by Sherrington in 1903 to describe these connections) held his attention thereafter.

The Physiological Society at their regular meeting in the 1930s then witnessed the battle between Eccles, promoting the electrical hypothesis for synaptic transmission, and Sir Henry Dale, Wilhem Feldberg and Martha Vogt, who championed the subsequently fully confirmed hypothesis of chemical transmission. The youthful (Sir) Alan Hodgkin had in 1937 published his crucial results establishing that the conduction of impulses along a nerve fibre depended on the flow of electricity in the nerve at the front of the impulse and Eccles took the view that such an event also enabled communication across the synapse.

At Oxford in 1927 he had married Irene ("Rene") Miller, a New Zealander, by whom he had four sons and five daughters. In 1937 he took his young family back to Australia. He became the Director of the Kanematsu Memorial Institute of Pathology in Sydney, where his professional resposibilities lay in providing a clinical pathology service. In this unlikely setting he put together an electrophysiological laboratory, recruited among others the biophysicist (Sir) Bernard Katz and the neurobiologist Stephen Kuffler, and continued work on neuromuscular transmission. During the Second World War he directed a blood replacement unit supplying operations in the Pacific.

His next move was to the Physiology Department of Otago University, in Dunedin, New Zealand (1944-51), where he developed a sustained attack on the excitatory and inhibitory transmission in the spinal cord of the cat. His obsession with his research in this rather arid environment overflowed into his undergraduate lectures, and earned him the sobriquet "Synaptic Jack" given by irreverent students. Among his lasting contributions was the inception of advanced undergraduate and postgraduate courses in physiology and the launching of students (including his daughter Rosamund) on their scientific careers in New Zealand and abroad. At this time he was still actively promoting the hypothesis of electrical transmission at nerve synapses in the spinal cord, basing his conclusions on the use of extra- cellular recording methods.

A crucial episode in the development of his ideas came from the introduction to the department by A.K. McIntyre, his successor as head of department, of a new technology - the hollow, electrolyte-filled, glass micro-electrode, which made it possible to make intra-cellular records of the activity of individual spinal nerve cell in situ. This revolution in technology came from J. Graham and R.W. Gerard in the United States. When the device appeared in his department, Eccles with characteristic insight and vigour promptly applied it to his experiments. He had already fully exploited the monosynaptic reflex pathway, and was able to use electrical stimulation of a muscle nerve to excite only nerve fibre with monosynaptic connections to large motor neurones in the spinal cord. By these means he was able to control in a very precise and necessary way the sensory input to these neurones.

He had also cornered the world's stock of Lucas pendulums (pre-electronic electro-mechanical instruments designed about 1910) and with these high- precision mechanical devices could deliver electrical stimuli to peripheral nerves at intervals less than 1 millisecond, which was necessary to cope with the speed at which events occur in the central nervous system. The results of inserting his recording electrode into a motor neurone led to the falsification of his electrical hypothesis. This caused him no problem since he had proved himself wrong, and it also rescued him from a cul-de-sac in which he was in danger of entrapping himself. Both excitatory and inhibitory transmission then became explicable in terms of chemical synaptic transmission.

His abrupt conversion from electrical to chemical transmission was revealed to an astonished physiological world at a meeting of the Physiological Society in London in 1951. In 1963 these studies earned him the award of the Nobel Prize in Physiology or Medicine, jointly with Sir Alan Hodgkin and Sir Andrew Huxley.

In 1951 Eccles had moved to the Chair of Physiology at the Australian National University in Canberra, at first to temporary hutted accomodation. There he built up a world-renowned research group, attracting gifted young investigators not only from Australia but from all four corners of the world. A veritable flood of research papers on the neurophysiology of the spinal cord and on transmitter substances in the central nervous system overwhelmed the scientific press, leading incidentally to the setting up in 1963 of a new journal, Experimental Brain Research. While at Canberra Eccles was instrumental in creating the Australian Academy of Science, modelled on the Royal Society of London, and was its President from 1957 to 1961.

In 1966, faced with prospect of mandatory retirement from the ANU, he uprooted himself and left Australia for the United States, never to return, not even to accept a medal from the Australian Neuroscience Society. At the Institute of Biomedical Research in Chicago, he rebuilt his research career, concentrating now on the brain, particularly the cerebellum. Subsequently he moved to the State University of New York at Buffalo. In 1968 he married Helena Tborkov, a research colleague in his Canberra days. After seven years at Buffalo he retired as a Distinguished Professor Emeritus to live and write books at Ca'a la Gra' in the Swiss Ticino, where he maintained an active liaison with former research colleagues.

Eccles always questioned "the relation between our bodies and our minds, and especially the link between brain structures/ processes and mental dispositions". He had known and been influenced by (Sir) Karl Popper in New Zealand and in 1974 they had the opportunity to spend a month at the Villa Serbeloni on Lake Como, engaged in a scientific dialogue. The result, The Self and Its Brain (1977) is a searching enquiry by "an agnostic philosopher" (Popper) and "a believer in God and the supernatural" (Eccles), actuated by the need to account for the human mystery from their standpoint of a dualism of mind and body. In conclusion, Popper said "So we leave it at that" and, one might add, to the future.

A prolific author of original research articles he also found time to write seminal books, sometimes based on invited public lecture, including: The Neurophysiological Basis of Mind (1953), The Physiology of Nerve Cells (1957), Sherrington, His Life and Thought (1979, jointly with William C. Gibson), The Human Mystery (1979). He also delivered prestigious lectures, such as the Waynflete (Magdalen College, Oxford), Ferrier (Royal Society), Sherrington (Liverpool University), and Gifford (Edinburgh University).

A formidable and devastating adversary in debate John Eccles nevertheless had many loyal friends among his numerous research colleagues and associates, some of whom celebrated his 90th birthday at a memorable symposium at the Max Planck Institute in Germany.

John Carew Eccles, neurophysiologist: born Melbourne, Australia 27 January 1903; Junior Research Fellow, Exeter College, Oxford 1927-32, Staines Medical Fellow 1932-34; Fellow and Tutor of Magdalen College, Oxford and University Lecturer in Physiology 1934-37; Director, Kanematsu Memorial Institute of Pathology, Sydney 1937-44; FRS 1941; Professor of Physiology, University of Otago, Dunedin 1944-51; Professor of Physiology, Australian National University, Canberra 1951-66; Kt 1958; (jointly) Nobel Prize for Medicine 1963; Member, Institute for Biomedical Research, Chicago 1966-68; Distinguished Professor and Head of Research Unit of Neurobiology, State University of New York at Buffalo 1968-75 (Emeritus); AC 1990; married 1928 Irene Miller (four sons and five daughters; marriage dissolved 1968), 1968 Helena Tborkov; died Locarno, Switzerland 2 May 1997.