Angus Brown, University of Nottingham, UK
“As a lab based scientist, I am convinced that Huxley’s happiest days were those spent in the lab directing his fierce intellect to the challenges that his research, be it nerve conduction or muscle contraction, posed,” writes Angus Brown (University of Nottingham, UK). In this tribute to Andrew Huxley, born on 22 November 1917, Brown celebrates Huxley’s legacy and tells us more about the remarkable talents and career of the Nobel Prize winning physiologist.
The Huxley surname is forever linked with The Physiological Society. Thomas H Huxley founded the Society in 1876 and his grandson, Andrew Huxley, gave his name to The Society’s headquarters in 2012 (Hodgkin Huxley House). As a youth Huxley was fascinated by how mechanical objects work and intended to become an engineer. He went to Cambridge in 1935 to study maths, chemistry and physics and only took physiology as a required scientific subject.
Giant axons
Huxley became acquainted with Hodgkin at Cambridge, who invited him on a trip to Plymouth in 1939 to carry out experiments on the newly introduced model of the squid giant axon, whose chief appeal was that its enormous relative size made it amenable to penetration by an intracellular metal electrode. However as always in science the devil is in the detail, and Huxley’s prime contribution came as a result of Hodgkin’s request to see how quickly a mercury droplet would fall through the axoplasm of a vertically placed axon.
As a youth Huxley was fascinated by how mechanical objects work and intended to become an engineer. He went to Cambridge in 1935 to study maths, chemistry and physics and only took physiology as a required scientific subject.
To their surprise the mercury remained static, and Huxley realised that a vertical alignment of the axon allowed cannulation with an internal electrode. It was by this simple realignment of the recording set up that Hodgkin and Huxley gained an advantage over American researcher Kenneth Cole, but this vertical alignment did require that manufacture of a new perspex perfusion bath. Huxley penetrated the axoplasm with a sharp needle prior to insertion of the metal electrode, to ensure the membrane was not damaged by subsequent insertion of the electrode. Hodgkin and Huxley succeeded in recording the first intracellular action potential, the report of which was duly published in Nature in 1939, an indication of the importance of this technical advance.
Action potential
However, the action potential profile both confirmed and refuted existing ideas about neural excitability, which had been proposed by Bernstein almost 50 years previously, namely that the resting membrane potential would be negative due to the membrane’s predominant permeability to K+ at rest. However, the action potential peak occurred at +40 mV, in contradiction to Bernstein’s prediction that the selective permeability of the membrane at rest to K+ would dissipate and the membrane would become equally permeable to all ions during activity and hence would approach 0 mV. The magnitude of this action potential peak strongly suggested a transient permeability to Na+, but this was not mentioned in either the initial 1939 report or in a subsequent longer paper published in 1945, a decision which in retrospect Huxley called stupid.
The start of the Second World War just weeks after Hodgkin and Huxley’s momentous recording instantly curtailed their experimental plan, and they devoted their time to the war effort. One must consider the feelings of Huxley, whose promise had led to an invitation by Hodgkin, who was clearly a scientist of immense talent and skill, and whose first experiments resulted in a publication in the world’s most prestigious scientific journal. The plethora of experiments suggested by the action potential were tantalisingly out of his grasp with the onset of war, and in America Kenneth Cole was at liberty to proceed with his experimental research (America did not join the war effort until over two years later), which had very similar goals to those of Hodgkin and Huxley. That Cole did not catch up with Hodgkin and Huxley highlights the brilliance of these two scientists, who, although they did not have Cole’s expertise in physics, did have the enormous advantage of a hands-on appreciation of biological processes.
There is a sense that those who achieve great things too young never live up to the expectations of their youth, but this was clearly not the case with Huxley.
Knighthood and accolades
There is a sense that those who achieve great things too young never live up to the expectations of their youth, but this was clearly not the case with Huxley. Hodgkin and Huxley resumed their experiments after the war ended, and devised the famous model that won them the Nobel Prize in 1963. During this frenzied period Huxley also devised brilliantly simple experiments to explain saltatory conduction in myelinated axons with Stampfli, and then in 1954 convincingly demonstrated the sliding filament theory of muscle contraction using a bespoke microscope of his own design and manufacture. Huxley devoted the rest of his scientific career to working on muscle, from which he must have derived profound satisfaction, considering Hodgkin could proprietarily claim ownership of the squid axon work having commenced the initial electrophysiology experiments in 1934, five years before he recruited Huxley.
Huxley’s legacy includes official recognition of his achievements in the form of a Nobel Prize and a knighthood, and serving as the President of the Royal Society later in his career, but as a lab based scientist I am convinced that Huxley’s happiest days were those spent in the lab directing his fierce intellect to the challenges that his research, be it nerve conduction or muscle contraction, posed.
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