Sir Andrew Huxley was one of the most distinguished physiologists of the twentieth century, doing elegant experiments that led to our understanding of two fundamental mechanisms: the mechanism that enables nerves to transmit information, and the mechanism that enables muscles to contract.

The grandson of Thomas Henry Huxley (‘Darwin’s bulldog’), Andrew was the son of the writer Leonard Huxley by his second wife Rosalind Huxley née Bruce, and had two famous half-brothers, Julian and Aldous. When he was about 12 he and his brother were given a ‘metal-turning, screw-cutting treadle lathe’, which he improved in his teens and used throughout his career. He was also given a small microscope, which started a lifelong interest in microscopy. In 1925 he joined University College School, but the later part of his secondary schooling was at Westminster. After he had been studying and enjoying classics for two years, his parents managed to persuade the headmaster that his real interests were in the sciences, and he switched to the science side, where he was, he said, ‘extremely well taught in physics’ and ‘also well taught in mathematics’.

In 1935 he joined Trinity College, Cambridge, with an open major scholarship, to read natural sciences. The first two years had to be spent on part one of the natural sciences tripos, and he had no hesitation in choosing physics, chemistry and mathematics. The regulations, though, required him to include a third experimental science and, on the advice of his friend Ben Delisle Burns, he chose physiology, on the grounds that it was ‘a lively subject in which even in the first year newly discovered things, and things still controversial, were taught’. This proved a wise choice, and by the end of his second year he had decided to focus on physiology for his part two examination, rather than physics. At that time, though, a successful career in physiology probably needed a medical qualification, so Andrew spent his third year (1937 to 1938) dissecting the human body, and the following year (1938 to 1939) taking the part two course in physiology.

In early August 1939, Andrew joined Alan Hodgkin in the Marine Laboratory at Plymouth, where Hodgkin was planning to do experiments on the giant nerve fibres of squids. Hodgkin suggested to Andrew that he might measure the viscosity of the axoplasm (or the cytoplasm within the axon of the neuron) by suspending the fibre vertically from a canula and seeing how fast droplets of mercury fell through the axoplasm. Unexpectedly, the drops became stationary as soon as they entered the axoplam, indicating that normal axoplasm is a gel rather than a liquid. Having got the fibre suspended in this way, though, they pushed an electrode down the fibre, so that with suitable apparatus they could measure the resting potential, and also the action potential when the fibre was stimulated. This was the first experiment of this kind and, contrary to the then current belief, during the action potential the potential difference across the membrane did not simply disappear but reversed, so that the inside of the nerve fibre became transiently positive relative to the outside. With war imminent, they left Plymouth – two days before Hitler invaded Poland – and wrote a short note to Nature reporting their very surprising result, but with almost no discussion.

Andrew had intended to do a couple of years’ of research, before starting his clinical studies, but with war ahead it seemed wrong to postpone such studies. He spent six months on an introductory course at Addenbrooke’s Hospital in Cambridge, and then six months as a clinical student at University College Hospital in London. But at the end of September 1940 teaching there was stopped because of bombing, and he moved into operational research for the Anti-Aircraft Command, working on the radar control of anti-aircraft guns. Later he was transferred to the Admiralty to work on naval gunnery.

It was not until 1946 that Andrew got back to Cambridge, took up the Trinity research fellowship he had been awarded in 1941, and resumed work with Hodgkin on the way in which nerves transmit signals. Sorting out what changes were occurring during the action potential faced two formidable difficulties. First, the whole action potential lasts only a few milliseconds. Secondly, the timing of events at any one point on the nerve will be slightly different from the events at adjacent points – either lagging behind or being ahead, depending on which direction the action potential is moving. They tackled both problems by using two wire electrodes wound on a thin glass rod that could be pushed along the inside of a squid giant nerve fibre, one to measure the voltage inside the fibre, the other, connected to an electronic feedback system (later known as a voltage clamp), designed to deliver whatever current was necessary to maintain a particular voltage, and to record that current. By imposing sudden changes of voltage of different size and duration, and noting the effects of changes in the composition of the fluid bathing the fibre, they were able to follow the changes in the conductivity of the membrane to sodium and potassium ions in a variety of situations.

It was clear that reducing the resting membrane potential by about 50 mV and holding it there caused a rapid but transient increase in the permeability to sodium ions, and a slower but maintained increase in the permeability to potassium ions. Reducing the membrane potential in a normal nerve fibre would therefore cause a rapid but transient increase in sodium permeability (and therefore entry of sodium ions, causing the membrane potential to be transiently inside-positive), followed by a slower increase in potassium permeability (and therefore loss of potassium ions, returning the membrane potential to its original value, and therefore also restoring the potassium permeability to its original value). At last the action potential was explained. It was a series of papers on this field by Hodgkin and Huxley, published in 1952, that led to their Nobel prize in 1963.

In 1952 Andrew switched his attention to the mechanism that produces contraction in striated muscle. For many years, observations of striated muscle fibres during contraction had produced very contradictory results, but in 1954, using interference microscopy, he and Rolf Niedergerke were able to show that length changes, whether produced passively by stretching or actively by stimulating the muscle, are the result of sliding movement relative to one another of two sets of filaments. A particularly elegant experiment by Andrew, working with A M Gordon and F J Julian (1966), showed that the force of contraction was proportional to the amount of overlap between the two kinds of filament.

In 1960 Andrew resigned from his readership in experimental biophysics in Cambridge and went to University College London, first as Jodrell professor and, from 1969 to 1983, as Royal Society research professor.

In 1980, Andrew, who had been elected to the Royal Society in 1955, had given the Croonian lecture in 1967, had received the Copley medal in 1973, been knighted in 1974, and been made a foreign associate of the National Academy of Sciences USA in 1979, became president of the Royal Society, a post he held until 1985. In 1983 he was awarded the Order of Merit, and in 1984 he was elected master of Trinity College, a post he held until 1990.

In 1947 Andrew married (Jocelyn) Richenda Gammell Pease, who died in 2003; they had five daughters and a son.

Ian M Glynn

[References:The Guardian 31 May 2012; The Telegraph 1 June 2012; The Independent 6 June 2012; The Economist 16 June 2012; The Lancet 2012 379(9835) 2422]