The Nobel connection

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1940s, 1950s, biochemistry, medicine, physics, physiology, research

Staff and senior students of the physiology department in 1951. Front row, from left: Laurie Brock, Ken Bradley, Prof Eccles, Eric Hook, Charlie Morris, Wilfrid Rall. Middle row: Arthur Chapman, Jack Coombs, Yap Tien Beng, Molly Bradley, Graham Jeffries, Pearl Cousins. Back row: Arnold Annand, Ron Stevenson, Dan Whyte. Photo courtesy of the Department of Physiology.

At first glance, the Otago physiology department’s one-page annual report for 1951 appears somewhat mundane. It listed student numbers, staff changes, research topics and publications, but it was a simple factual report and made no comment on the teaching workload (which was heavy), research productivity and quality (high), or the achievements of departing staff (remarkable).

A closer look at the 7 publications listed provides further insight into goings-on in the department. Two appeared in the leading journal Nature: ‘Plasticity of mammalian monosynaptic reflexes’, by departing professor Jack Eccles and senior lecturer Archie McIntyre; and ‘The afferent limb of the myotatic reflex arc’, by McIntyre. Several others appeared in the local publication Proceedings of the University of Otago Medical School, including ‘Action potentials of motoneurones with intracellular electrode’, authored by physiology lecturer Laurie Brock (a recent Otago medical graduate), physics lecturer Jack Coombs (another Otago graduate) and Eccles. That article – just a page and a half long – was the first published report of an important breakthrough in neurophysiology research; it was a significant step in the work that won Eccles a Nobel Prize in 1963.

Eccles, born in Melbourne in 1903, commenced at Otago in 1944, bringing impressive credentials from his years as a physiology researcher in Oxford and Sydney. He replaced John Malcolm, who had been physiology professor since 1905. Malcolm was an active researcher, highly respected for his work in biochemistry and nutrition, but Eccles was to take the research activity of the department to a new level. First, though, he had to reacquaint himself with the whole of physiology in order to teach medical students, something he had not done for some years. Preparing 75 lectures for second-year meds, plus others for first-year meds, along with a completely new laboratory course and discussion groups, meant his research ‘virtually came to an end’ during that first year, Eccles later recalled. He did design some of the medical students’ lab work to assist his research, as Miles Hursthouse explained: the professor ‘conducted many interesting experiments, some of them on us! At our practical sessions we had to endure having needles stuck into a muscle, then contract that muscle while measuring the electrical impulse and rate of propagation’. There weren’t many staff to assist, though Eccles was grateful for those he had, including Norman Edson, appointed associate professor of biochemistry in 1944. Biochemistry was a rapidly-growing field, and in 1949 it split from physiology to become an independent department with Edson as inaugural professor; the two fields continued to work closely together despite the administrative separation.

Though he had little time for research in 1944, it was ‘important in my scientific life above all my post-Sherrington years’, recalled Eccles (Charles Sherrington being the distinguished neurophysiologist who inspired him at Oxford). It was then he met the great philosopher Karl Popper, who was teaching at Canterbury. Hearing of the stir that Popper was creating among the scientists of Christchurch, Eccles and Edson invited him to visit Otago. Eccles was heavily influenced by the ‘inspiring new vision of science that Popper gave us’, most notably by his message ‘that science is not inductive, but deductive’. With Popper’s urging, Eccles set about designing experiments that would test a hypothesis ‘in its most vulnerable aspects in an attempt at falsification’. He was keen to prove his theory that messages crossed the synapses of nerve cells by electrical rather than chemical means.

By 1945 Eccles was busy experimenting alongside his teaching duties. David Cole, future dean of the Auckland medical school, completed a BMedSci degree with Eccles that year, recalling that ‘the ebullient JCE’ had ‘ideas tumbling out of his mind’; students appreciated ‘the invaluable experience of working close to the edge of scientific knowledge’. The professor’s lab was ‘a huge cage of chicken wire’ and ‘almost a caricature of the mad scientist amongst his oscilloscopes, wires and animals’. Another student recalled the day that Eccles ‘arrived in great excitement, having, he said, a testable hypothesis about inhibition which had come to him, like Archimedes, in the bath that morning. He retired to his wire cage for 24 hours or more, being fed sandwiches through the door’.

Neurophysiology experiments required sophisticated and intricate electronic equipment; Eccles acknowledged that such technology ‘rapidly outstripped my understanding …. My indebtedness to my associates is immeasurable’. In his travels around the world, he noted, ‘I have left … a trail of elaborately designed shielded research rooms stripped of equipment!’. To Otago he brought not just specialist electrical equipment, but also a technician, Arthur Chapman. He also made the most of the technical expertise he found in Dunedin. Arnold Annand, whose electrical expertise had been honed during service in the Air Force, joined the physiology department as a technician in 1948, beginning a career of almost 40 years building and maintaining equipment for the university’s health science departments. In 1950 Eccles asked Jack Coombs, a ‘shy genius’ who had been lecturing in the physics department since 1940, to design a machine capable of the electronic stimulation and recording he needed for his experiments. Coombs came up with devices which remained, for many years, ‘the best general research instruments for electrophysiology in the world’, said Eccles. Coombs also participated in the neurophysiology experiments. Eccles attracted PhD students – then a rare breed – to Otago. For instance, Wilfrid Rall, a Yale graduate, came to study with Eccles, remaining on as a lecturer for several years before returning to pioneering neuroscience work in the US. Another important recruit to the department was Archie McIntyre, an old Australian neurophysiology colleague. Eccles convinced McIntyre to join him at Otago, where he became senior lecturer in 1949.

Eccles at work on an experiment, assisted by Molly Bradley, in 1951. Photo courtesy of the Department of Physiology.

The breakthrough 1951 experiment required the insertion of a tiny electrode, less than a micrometer wide, into a single nerve cell in the spinal cord of an anaesthetised cat; the action potentials of the cell could then be measured. Similar experiments had been carried out on frog muscle fibres, but never successfully on mammals. The day that revealed that synaptic action was chemically mediated, thus disproving Eccles’s theory of electrical transmission, was remarkable not only for that result. The experiment lasted for many hours, but for some time Eccles was left to tend it alone while one of his colleagues, Laurie Brock, delivered the baby of the wife of the third member of the team, Jack Coombs! As an enthusiastic disciple of Popper’s deductive method, Eccles was happy to accept that his theory was false, becoming a ‘belated’ convert to English neuroscientist Henry Dale’s hypothesis of chemical synaptic transmission even in the central nervous system.

Although Eccles was to carry out further ground-breaking experiments in neurophysiology, they didn’t take place in Dunedin. At the end of 1951 he departed for a plum job as founding physiology professor at the John Curtin School of Medical Research, attached to the recently-established Australian National University, Canberra. There he could carry on his research without the distraction of the heavy teaching load which he found a burden at Otago. Jack Coombs (whose younger brother Doug was geology professor at Otago for many years) and Arthur Chapman followed Eccles to ANU, as did some of the specialised equipment. But he left behind a strong legacy of experimental neuroscience at Otago and, by no means least, his much-respected colleague Archie McIntyre, who succeeded him as physiology professor. Under McIntyre’s leadership the department continued to attract talented research students and staff and maintained a strong experimental focus, albeit one less focused on neurophysiology, as new staff with other interests within physiology joined the team.

Ted Jones, who became a prominent neuroscientist in the USA, arrived at Otago as a medical student a few years after Eccles departed. He could not recall ever being told that Eccles had carried out groundbreaking work ‘in one of those rather grubby basement rooms of the Lindo Ferguson building. If Eccles was remembered at all it was for his irascibility, not his scientific achievements’. Perhaps the subsequent award of a Nobel Prize alerted later students to what this man had achieved in the world’s southernmost medical school – certainly it’s something we can celebrate today!