Summer 2014 marked the 75th anniversary of a ground-breaking experiment undertaken at the Laboratory of the Marine Biological Association by Alan Hodgkin and Andrew Huxley that helped launch a golden era of neurobiology.
In July 1939 the pair travelled from Cambridge University to Plymouth to work on the giant nerve fibre of the squid Loligo. The way had been prepared for their landmark achievement by the Oxford zoologist J.Z. Young (MBA President 1976–1986) who, in 1929, unexpectedly found the giant nerve fibres of Loligo while looking for an epistellar body (a vestigial photoreceptive organ), such as he had already discovered in the octopus Eledone. Instead, Young found a group of nerve cell bodies. Working at the MBA, Young noticed that from each cell projected a fine process, and that some 300 to 1500 of these processes were fused, forming the giant axons—crucially having ‘large’ diameters up to 1.0 mm that were suitable for insertion of a fine electrode. Young had confirmed experimentally that the structures were nerve fibres. However, it was left to Hodgkin and Huxley to probe the axon’s inner workings.
Their first experiment in the summer vacation of 1939 investigated the nature of the nerve fibre contents. Finding it to be a solid gel and not a viscous liquid, Hodgkin had the insight to realize a fine saline-filled glass tube containing a chlorided silver wire could be pushed down the giant fibre to act as a non-polarizable electrode. With this set-up they were able to record the potential difference between the interior and exterior of the fibre using equipment Hodgkin had built and found the internal ‘overshoot’ of 40–50 mV above the external potential, the hallmark of the action potential.
After checking their results several times into late August 1939, and with the Second World War imminent, they left Plymouth and published their findings in a now famous letter to Nature (Action potentials recorded from inside a nerve fibre. Nature 144, 710–711; 1939). Follow-up work for Hodgkin and Huxley became impossible for another eight years with the pair engaged in war work, during which time the MBA Laboratory was badly damaged by bombing and all the electrophysiology equipment destroyed.
Starting again at the MBA in mid-June 1947, and continuing through the 1948 and 1949 squid ‘seasons’ using the new voltage-clamp technique, they managed to record propagating nerve impulses culminating in their quantitative theory of nervous conduction published in a seminal series of papers in 1952. A share of the Nobel Prize for Physiology or Medicine in 1963 followed.
Research using squid giant axons as a model system greatly expanded in Plymouth over the four decades following the first announcement in Nature, and involved such scientific luminaries as Bernard Katz and Richard Darwin Keynes. Obtaining recordings was technically very difficult and presumably it was the relief of finishing a fibre that started the tradition among the squid scientists of throwing them upwards over the shoulder with such speed that the sticky fibres became stuck fast to the ceiling! Some are still preserved in situ at the MBA (pictured) to commemorate the hugely important work done there, and to celebrate its ushering in of modern electrophysiology and the myriad of important discoveries in neuroscience that have followed.
Professor David Sims (firstname.lastname@example.org) MBA Senior Research Fellow.
Sims, D., (2014, October) Inside the squid giant axon. The Marine Biologist, 3, 28.