Biology Reference
In-Depth Information
in biology and medicine. They also disclose the limitations of this kind of
physics-oriented approach to biology, and a comparison of those areas where
mathematical modeling works and at what points it begins to fail may indicate
ways that systems biology can approach the issues of theories, models, and
equations in this nascent area.
I will begin my discussion with a brief account of the development of the
Hodgkin-Huxley Giant Squid Model for Action Potentials, a stunning accom-
plishment for which Hodgkin and Huxley shared the Nobel Prize in physiology
or medicine in 1963. One of the current standard textbooks of neuroscience
(Kandel et al. 2000) states that 50 years after its publication, 'the Hodgkin-
Huxley model stands as the most successful quantitative computational model
in neural sciences if not all of biology' (p. 156).
1
2. THE DEVELOPMENT OF THE HODGKIN-HUXLEY GIANT
SQUID MODEL FOR ACTION POTENTIALS AS A CLASSICAL
EXAMPLE OF SYSTEMS BIOLOGY
Action potentials are waves of potential difference (or voltage) that move down
nerve axons, communicating the effect of a stimulus from the receptors located
near the beginning of the neuron to the termination of the nerve cell. To a first
approximation, action potentials are the result of rapid (millisecond) changes
in the membrane's permeabilities to sodium and potassium ions, changes that
underlie the wave of potential difference. Hodgkin and Huxley's work on the
action potential in nerve cells began from Hodgkin's earlier work on electric
currents on the shore crab in the late 1930s (Hodgkin, 1964). He teamed up
with Huxley, who was his student at Cambridge University, and they jointly
turned their attention to the giant squid axon, which was a much more tractable
experimental system to investigate the movement of specific ions, including
sodium and potassium. Though their work was interrupted by World War II,
they resumed their project in 1946, and in the late 1940s through to the early
1950s they conducted their classical experimental and theoretical investigations
(Huxley, 1964). A series of papers culminated in their extraordinary 1952 article
in the
Journal of Physiology
in which they systematically lay out the steps and
their reasoning that culminates in the classical action potential model of nerve
transmission (Hodgkin & Huxley, 1952).
The 1952 paper closely parallels their more historical account of their steps
toward their quantitative model that appears in the two Nobel Prize lectures
1
The philosophy of science literature has just recently begun to address the Hodgkin-Huxley action potential
model as an important exemplar. Weber (2004) discusses it at some length in Chapter 2, and Bogen (2005)
and Craver (2006) analyze it as well.
