Hodgkin and Huxley’s modelling of the action potential

The representation of biological processes by mathematical equations, known as modelling, is a modern phenomenon; the focus on R-values in relation to the spread of COVID-19 is one example.

Modelling has been facilitated by the ubiquitous presence of desktop computers and the development of bespoke supercomputers. The most admired and respected model in the field of physiology is that devised by Alan Hodgkin and Andrew Huxley in 1952 to quantify the permeability changes that underlie the action potential.

Hodgkin’s great-great uncle described the eponymous lymphoma in 1832, and Huxley’s half brother Aldous wrote Brave New World in 1932; both were members of The Physiological Society, co-founded by Huxley’s grandfather TH Huxley in 1876.

Hodgkin and Huxley displayed great clarity of thought in the generation of their model. They had to overcome numerous obstacles including time constraints, limited resources, an 8-year interruption of their experiments caused by World War 2, and unpredictable performance of electrical equipment, all of which precipitated a distillation of disparate ideas into a cogent narrative that could be expressed in a few key concepts that they tested experimentally.

After acquiring and analysing the data they developed the equations comprising their model. The model was of impressive predictive power and successfully reproduced the action potential. However, it required over a million individual calculations to an accuracy of 6 decimal places on a hand cranked computer, which explains the delay of 3 years between their final experiments and the publication of the papers.

Although the model derived from experiments carried out in squid giant axon its impact was universal as it was broadly applicable to all excitable membranes, and Hodgkin and Huxley were rewarded with the Nobel Prize for Physiology or Medicine in 1963.