The Nobel Prize in Physiology or Medicine 1944
In regard to Erlanger's and Gasser's works, Professor R. Granit, Head of the Department of Neurophysiology of the Nobel Institute of the Royal Caroline Institute, made the following statement*.
Three
great electrophysiological discoveries can be regarded as milestones in the development
of our knowledge of nerve physiology. In the middle of the last century, long
before Alfred Nobel had bequeathed this great fund to the world, Du Bois-Reymond
showed that the nerve impulse was an electrical wave of negativity transmitted
along the nerve. Helmholtz made the first measurements of its average speed of
propagation in a nerve stem. The second great discovery, rewarded with a share
in the Nobel Prize for 1932, was Adrian's observation that sense organs and nerve
cells discharge whole series of such impulses. In each individual fibre the nerve
impulse is of constant size but the stronger the stimulus, the greater the frequency
of the impulses discharged along the nerve. The nerve cells, as it were, communicate
with each other by a kind of machine-gun fire. This description of the mechanism
is inadequate from the standpoint of physics but otherwise illuminating. And,
indeed, if the impulses are led to a loudspeaker over an amplifier it does sound
like machine-gun fire. The discoveries of Erlanger and Gasser constitute a third
step forwards.gasser-lecture.pdf
In 1907 the Swedish physiologist Gustaf Göthlin made the assumption that
conduction velocity in thick nerve fibres is greater than in thin ones. The basis
for this view was W. Thompson's formula for electrical-cable conduction. This
assumption gave a physiological interpretation of the well-known fact that the
individual fibres of a nerve stem vary in cross section. Some fibres are less
than 0.001 mm in diameter, others just above 0.020 mm. Lapicque and his colleagues,
from 1913 onwards, published some papers in which indirect evidence in support
of this view was advanced. In a series of remarkable papers - remarkable in respect
of both technique and wealth of new information unearthed - Erlanger and Gasser
proved this hypothesis to have been correct. As so often happens in experimental
sciences, the additional steps necessary for full clarity as well as the development
of an elegant new technique, heralded an experimental expansion of great width
and significance. The seemingly simple cables turned out to have been endowed
with a high degree of differentiation. Since nerve fibres are to be regarded as
extensions of nerve cells these results are indeed of extreme importance for the
physiology of the higher centres such as the brain and the spinal cord. This fact
should be given especial consideration in appraising the significance of the work
of Erlanger and Gasser.
Erlanger and Gasser showed that the nerve
fibres, according to their conduction velocities, could be divided into three
main groups of which the first, group A, could be further subdivided. The thickest
mammalian fibres, the A-fibres, conduct impulses as fast as from 5 to 100 metre
per second, the thinnest, the C-fibres, have conduction velocities below 2 metre
per second. Between these two groups there are the B-fibres with conduction velocities
from 3 to 14 metre per second. A large number of other properties of the nerve
fibres vary with the speed of conduction, for instance, the duration of the impulse,
its rate of rise, its size, the duration of the inexcitable or refractory period
following each impulse, the threshold of excitation, the sensitivity of the discharge
to pressure on the nerve and to asphyxia, in short, an array of properties connected
with impulse conduction all of which need not vary in an exactly parallel manner.
Erlanger and Gasser also showed how this highly differentiated system with its
three main types of fibre was distributed over the in- and outgoing fibres of
the spinal cord, the so-called sensory and motor roots. The perception of pain
is largely mediated by very thin, slowly conducting fibres, muscle sense and touch
by rapidly conducting fibres. The muscles of the body are also thrown into movement
by fast fibres.
In the brain and the spinal cord the time ratios
of the impulses are of primary importance for the cooperation of the nerve cells.
A difference of 0.001-0.005 seconds in the time of arrival of impulses means that
a given path may be found opened or closed for their passage onwards. Problems
of this kind belong to the present-day programme of experimentation in these fields.
The admirable technique of Erlanger and Gasser soon showed them a road
to new discoveries, chiefly concerned with the changes of excitability that occur
at a nerve cross section at which impulses arrive. The arrival of one or several
impulses to such a region was found to be followed by slow changes of excitability
which were associated with slow changes of electrical potential, studied in detail
by Gasser. These changes of excitability enhance or depress succeeding impulses.
Such «after-potentials» had been seen before, but Gasser and his collaborators
demonstrated their independent character and showed that they behaved in a different
manner in the three main types of fibre. The concept of a high degree of differentiation
of the nerve fibres for their different tasks was thus again supported by a new
group of facts. These are of particular importance for the physiology of the central
nervous system. A prominent feature of this region is interaction between excitation
and inhibition in close association with slow potential changes. Erlanger and
his collaborators devoted themselves to an analysis of the changes of excitability
in a nerve influenced by a constant electrical current. One of their most important
discoveries was the demonstration that sensory nerves in many respects differed
from motor nerves. The sensory nerves had, for instance, lower thresholds of excitation
and they put up less resistance to impulse generation (less «accommodation»)
than motor nerves. This fresh contribution to the differentiation among the nerve
fibres has far-reaching consequences.
When today Erlanger and Gasser
receive the 1944 Nobel Prize for their discoveries concerning the highly differentiated
properties of single nerve fibres, it might be pointed out that their achievement
was not born, fixed and armoured, in the manner of the birth of Pallas Athene.
But no sooner had their first result given them the key word than discovery followed
hard upon discovery until their colleagues everywhere in the world came to realize
that a great new synthesis had been born to nerve physiology. This synthesis is
based on new facts, well-hardened by a masterly technique cementing them into
a groundwork on which will be erected whatever structure the future has in store
for the physiology of the central and peripheral nervous system.
*Broadcast lecture delivered on the 10th December, 1944.
From Les Prix Nobel en 1944, Editor Arne Holmberg, [Nobel Foundation], Stockholm, 1945
