wiring up biology





Wiring up biology

COPYRIGHT 1992 The Economist Newspaper Ltd. All rights reserved.

WHEN the commonplaces of one discipline are applied to an unrelated field,
they can prove curiously fruitful. In 1952 two British physiologists, Alan
Hodgkin and Andrew Huxley, managed just such a fruitful crossover, applying
textbook physics to living tissue. They were both later knighted, and
shared a Nobel prize in 1963. The experimental method they pioneered
remains fundamental to research into the behaviour of nerve cells.

As anyone who has ever had an electric shock knows, electricity has
powerful effects on living matter. Luigi Galvani found in 1771 that
electricity could make the muscles from frogs\' legs contract; soon
afterwards, physiologists came to suspect that all sensation and movement
depended upon electric pulses in nerve and muscle. But how does electricity
pass through living things?

By the time Dr Hodgkin and Dr Huxley (as they then were) came to these
questions, other researchers had discovered various things about nerve
cells. One of the most intriguing was that messages down nerves are as loud
when received as they were when transmitted--unlike messages sent down
cables, which attenuate with distance. Physiologists thought that this
active transmission had something to do with sudden and short-lived changes
in the electrical resistance of a nerve fibre\'s outer membrane. The link
between transmission and changing resistance was the subject of decades of
increasingly intense speculation.

Progress was slow because the nerves were not, as the police put it,
assisting in the inquiries. Nerve fibres are made of axons, which are
hairlike protrusions that grow out of nerve cells. They are small and
delicate, unforgiving of rough treatment. The surges in the voltage across
the cell membrane, now called action potentials, are complex events lasting
only a couple of milliseconds. Difficulties with delicacy and speed often
thwarted the physiologists working on nerves before the second world war.

Another problem was the action potential\'s uncompromising nature; it is
either present at full strength or absent altogether, never anything
in-between. Such all-or-nothing behaviour is a nightmare for scientists. It
means that varying the stimulus for an action potential causes no variation
in the response. It is from studying such variations that mechanisms are
normally revealed.

Throughout the 1930s Dr Hodgkin had been exploring electrical conduction in
nerves with some success, using many of the tools that he and his student
Dr Huxley were to exploit in their classic experiment. Many of these came
from America, where there were engineers skilled in producing the sensitive
electronic apparatus that was needed. In Cambridge, where Dr Hodgkin and Dr
Huxley had fellowships, physiologists had to build their own apparatus with
components bought from a local wireless shop. Another American import was
the object of study: giant nerve-fibres found in squid, as much as 40 times
larger than the largest vertebrate nerves, and thus far easier to dissect.
Despite these tools, though, the nature of the nerve proved elusive.

The difference between Dr Hodgkin\'s pre- and post-war work is simple: the
war. Like other scientists, Dr Hodgkin and Dr Huxley broke off their
research when Britain declared war on Germany. Though train-ed as
physiologists, they were put to work in fields with a direct bearing on the
war effort: Dr Hodgkin worked on radar, Dr Huxley developed sights for
naval gu********************************************************************************************************************************************************************************************************************************************************************************************************************************************************************************************************************************************************************************************************************************y
Cole, who was another great influence on the Cambridge pair, and unlucky
not to share their Nobel laurels.

Clamped

An axon is a long tubular outgrowth from a cell, wrapped in a cell
membrane. One of the differences between the outside and the inside of the
cell is the concentration of various types of ion--atoms carrying electric
charge. To take one example, cells contain a high concentration of
positively charged potassium ions.

If the membrane becomes permeable to potassium ions, they will leak out of
the cell into the fluid outside. Force of numbers drives them from places
where they are concentrated to places where they are scarce. If the
membrane stops negatively charged ions joining the exodus, an electrical
potential, or voltage, quickly builds up across the membrane as positive
charge leaves the cell. Eventually that voltage becomes strong enough to
stop the flow of potassium. The electrical force encouraging the ions to
stay in the cell becomes as strong as the force driving them out.

The cell can quickly overturn this balance, though, by making its membrane
porous to other ions. These charged particles will flow to where they are
less common, just as potassium did, until a new balance between electricity
and concentration is struck. To the outside world, the movement of charge
shows up as a sudden change in the voltage across the membrane--an action
potential.

Dr Hodgkin and Dr Huxley