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1901 2012
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The Nobel Prize in Physiology or Medicine 1924
Willem Einthoven
Award Ceremony Speech
In regard to Einthoven's work, Professor J.E. Johansson, Chairman of the Nobel Committee for Physiology or Medicine of the Royal Caroline Institute, made the following statement*
The Staff of Professors of the Royal
Caroline Institute has on 23rd October, 1924, decided to confer
this year's Nobel Prize in Physiology or Medicine to the
Professor of Physiology at the University of Leiden, Willem Einthoven, for his
discovery of the mechanism of the electrocardiogram.
Einthoven's name is linked partly with the design of a physical
instrument, the string galvanometer, partly with the
so-called electrocardiogram, a record of the electrical
potential fluctuations at the surface of the body, which
accompany the heart beat. The heart beat, like the piston
movement of a steam engine, is a cyclic process. Behind this
process lies, in the first place, a similarly cyclic process in
the heart muscle.
For the present this process is called the «muscular
process», in analogy with «neural process» and
«glandular process». All these processes, which with
regard to energy must be considered as a conversion of chemical
energy into forms of energy other than heat, are accompanied by a
fluctuation in the electrical potential - the action current -
which as a rule is extremely weak and which does not play any
role in the life of the individual, but which from the viewpoint
of experimental technique, however, is of the greatest interest,
in so far as it allows the registration of the frequency of the
functional process and its propagation through the individual
organs.
The potential fluctuations concerned are measured in millivolts
and in hundredths of seconds. To construct a self-registering
measuring instrument which records directly and truly the
potential variations of this order of magnitude was a problem
which Einthoven has solved with his string galvanometer
(1903). In constructing this, he started from the well-known
Deprez-d'Arsonval «moving-coil galvanometer» and had
herein replaced the moving parts - coil and mirror - with a fine,
silver-plated quartz wire, which was stretched in the field
between the poles of the magnet and at the same time between an
optical illumination system, and another one for projection. The
reduction in mass of the moving parts, achieved in this way,
allows at the same time high sensitivity and short adjustment
time.
After testing the practicability of the instrument for various
purposes, and after a thorough analysis (1906) of the dependence
of the string galvanometer curve on the mass and tension of the
string, and on the damping of the deflection, the latter by
electromagnetic means and by the effect of the air resistance,
Einthoven published in 1909 the first detailed description of the
instrument. Interest in the string galvanometer spread very
rapidly, and string galvanometers of various types after
Einthoven's specifications were supplied by several famous
instrument firms.
Using strings of ultramicroscopic size in a vacuum between the
poles of a magnet, Einthoven recently succeeded in registering
potential fluctuations of a frequency far beyond the limits of
known physiological phenomena. In this connection it may also be
mentioned that he has registered sound waves with a frequency of
more than 10,000 vibrations per second, by means of strings of
the dimensions previously mentioned in association with suitable
optical systems.
The construction of the string galvanometer was a purely physical
problem. The interest shown by physiologists and physicians in
this achievement, is caused, as already mentioned, by the
possibilities of analysing, by means of the registration of the
so-called action currents, some phenomena in the living organism.
The string galvanometer has therefore been widely used for
various purposes in physiology. To give an idea of this, some
phenomena may be mentioned, which by means of the string
galvanometer have been investigated by Einthoven himself: the
retina current (1908, 1909), the action currents in nervus vagus
(1908, 1909) and in the sympathetic chain (1923), the
psychogalvanic reflex (1921), the Gaskell effect (1916), the
muscular tone (1918). With regard to the action current of the
muscle Einthoven demonstrated (1921) in a convincing manner that
this occurs exclusively as a phenomenon accompanying the
mechanical effect known for a long time - a fact very important
to the concept of the action current.
The achievement for which the Staff of Professors of the Royal
Caroline Institute awarded Einthoven the Nobel Prize, is in the
field of the heart physiology. Einthoven's interest in the
action current of the heart dated from 1891; at that time,
as a result of the investigations of Burdon-Sanderson (1879) and
Augustus Waller (1887, 1889) attention was focussed on this
phenomenon.
Both scientists used the well-known Lippmann capillary
electrometer, which registers potential variations; but the
adjustment time is rather long, and the capillary electrometer
curve, therefore, does not reflect in a direct manner the actual
time process of the potential changes in the heart muscle during
heart beat. Einthoven developed a rather simple method of
correction (1894) and could with this derive the actual
electrocardiogram from the capillary electrometer curve
(1895). The details herein he denoted as P, Q, R, S, T: terms
which are preserved to this day. This method, however, would
never have any practical significance in reproducing the
electrocardiogram of man. It is much too laborious for this.
Einthoven saw the importance of an instrument which
directly renders the potential variations with time during
these processes, and the result was the string galvanometer
described above (1903). The curve recorded by this instrument
during the registration of the action current of the heart showed
perfect agreement with the electrocardiogram derived from the
capillary electrometer curve, and this agreement between the
results of the two registration methods, fundamentally so
different from one another, proved beyond all doubt that the
actual time process of the potential variation accompanying the
heart beat had been obtained. Einthoven can thus with full
justification be named the discoverer of the real
electrocardiogram.
One of the first results of this discovery was the demonstration
that each individual has his own characteristic
electrocardiogram, but that the electrocardiogram of all
individuals in the main conform to a general type. In a
publication «Le télécardiogramme» (1906)
Einthoven returns to the same subject, revealing, however, at the
same time a fact which has acquired the greatest clinical
significance: that different forms of heart disease reveal
themselves characteristically in the electrocardiogram. He
gives examples of the electrocardiograms of patients with
hypertrophia of the right ventricle during mitral insufficiency,
hypertrophia of the left ventricle during aorta insufficiency,
hypertrophia of the left auricle during mitral stenosis, of
patients with degeneration of the heart muscle, also of
electrocardiograms during various degrees of heart block, during
extrasystoles, true «atypical heart systoles» of two
different types, as well as during what is now called
«ataxia cordis». In a subsequent work «Weiteres
über das Elektrokardiogramm» (More about the
electrocardiogram) in 1908, he communicates other cases.
Einthoven's interest for the electrocardiogram from clinical
point of view is also evident from a proposal, put forward by
himself (1906), namely, to establish so-called telecardiograms,
i.e. to have electrocardiograms produced by a string galvanometer
in a physiological laboratory from patients lying in a hospital
several kilometers away. Nowadays, since a string galvanometer is
available in almost any large hospital, this detail is only of
historical importance.
It can be said that this new method of investigation fulfilled
a need in clinical medicine. One needs only to remember the
curves of venous and arterial pulses, and cardiograms at disposal
up till then - all of them difficult to interpret - whenever a
case of arrhythmia had to be cleared up. Moreover, some
«stroke of luck» was indispensable, even if one is a
well-trained experimentator, to obtain a «mechanical»
cardiogram from a person, which entirely corresponds with one
taken some hours before. The string galvanometer, on the other
hand, once set up and adjusted, operates ideally,
«accident»-free.
What did the electrocardiogram mean at that time? Einthoven said
in his work in 1895 that the efforts to fully interpret the
electrocardiogram should be abandoned for the moment, and in a
survey of the relevant literature up to the first half of 1912,
the author** put emphasis on the
uncertainty of the efforts to interpret the cardiogram. It can
therefore be said that Einthoven had in 1895 discovered some sort
of writing the contents of which for many years after remained in
virtual obscurity.
However, in his work in 1908 Einthoven gave an interpretation
of the electrocardiogram. He starts from the fact that the
stimulus (of the contraction process, the «negativity»)
is propagated as a wave in the muscular system of the heart. The
string of the galvanometer, connected with the heart in a closed
circuit in one of the usual ways, remains in the original
position not only when the heart is at rest, but also when the
«negativity» of the assemblage of points of the heart
wall show the same value. A deflection is therefore in the first
place to be expected at the beginning and at the end of a
systole, and it presupposes that the condition of activity does
not occur, respectively cease, simultaneously in all elements of
the muscle. Further: if the contraction process (the stimulus) is
propagated symmetrically in relation to the points connected to
the galvanometer, then no deflection would take place either.
Under such circumstances the electrocardiogram must be determined
partly by the starting-point of the stimulus to the heart beat,
partly by the conduction system within the heart. The point of
departure for the normal heart beat has been sufficiently well
known since the middle of the 1890's, the bundle of His also
since that time, and Tawara's description of the ramification of
the conduction system inside the ventricles known since 1906.
According to Einthoven the P-peak is an expression of the
propagation of the stimulus wave in the muscular system of the
auricle. The negativity wave, corresponding to the stimulus wave
in the His-Tawara system, is considered too weak by Einthoven to
cause any deflection in the galvanometer. The QRS-complex is
determined by the propagation of the stimulus wave in the
muscular system of the two ventricles, proceeding in
unsymmetrical fashion to the points of lead, starting at
different moments at the transition of the tree-like ramified
Purkinje's fibres into the various parts of the proper muscular
system of the heart. When the contraction process has reached its
maximum in all the points of the ventricular wall, the string
returns to its original position. When the contraction ceases in
the various parts at different moments, a T-peak is
obtained.
It is unnecessary in this connection to consider the
interpretations proposed by other investigators, as
Einthoven's concept is the only one which has proved to be
tenable. The interpretation that the P-peak belongs to the
auricular systole is mainly based on his observation of
electrocardiograms in cases of heart block in patients or during
vagus stimulation in dogs. With regard to the interpretation of
the QRS-complex Einthoven was evidently the first who has clearly
recognized the significance of the conduction system in
this connection. The train of thought in the interpretation of
the T-peak can already be detected in Burdon-Sanderson's
previously mentioned work.
Already Waller (1887) had observed that the deflections of the
capillary electrometer vary accordingly as the lead is taken from
both hands or from one hand and one foot, etc., and based
hereupon his well-known scheme of the potential distribution in
the body in relation with the heart's action current - a scheme
later adopted in textbooks and handbooks. The scheme has
principally been used to demonstrate that the amount of
deflection, i.e. the «peaks» in the electrocardiogram,
must vary in accordance with the manner in which the electrodes
have been applied in relation to the heart axis. Einthoven
pointed out, however, that not only the amount of the deflection
but also the shape of the entire electrocardiogram is changed
when one manner of leading is replaced by another (1908). One
of the spikes may be accentuated while another may be suppressed,
etc. One and the same spike resulting from different leads does
not always correspond with the same phase of the heart period.
Einthoven therefore found it essential to always indicate the
manner of leading, and in connection with this he proposed (1908)
the now generally accepted standardization: Lead I, II, and
III.
In a publication (1913) Einthoven has shown how the direction
and definite amount of the resulting potential difference at
corresponding moments can be calculated from the simultaneous
deflections at the three leads indicated. The direction of the
resulting potential variation corresponds in a certain way to the
electrical axis in Waller's scheme, and several authors use the
term «electric axis» instead of Einthoven's
designation. Waller made this axis to coincide with the
anatomical axis of the heart, an obvious procedure, since at that
time it was generally believed that the heart - as to the
propagation of the stimulus wave - could be identified with a
muscle with fibres running parallel, stimulated at one end. In
fact, the resultant potential variation (the «electric
axis»), as shown by Einthoven, changes its direction from
one moment to the other during the heart period. The rotation of
the electric axis during the heart period is nothing else than an
expression of the course of the stimulus wave through the heart
muscle, as is evident from the electrocardiogram at the three
leads indicated. Already in his papers in 1906 and 1909 Einthoven
pointed out on the basis of the shape of the electrocardiogram
that the starting-point for the so-called atypical ventricular
systoles must be other than for the normal, and showed that a
combination of electrocardiograms at different leads supplies a
possibility of deciding where this starting-point is located. The
calculation of this direction of the resultant potential
variation is a refinement of this method which can be used when
an evaluation of the electrocardiogram by visual inspection is
not sufficient.
Such a calculation is very simple. The difficulty consists in
establishing the corresponding phases in the combination of
electrocardiograms at the three leads. Hereby, as pointed out by
Einthoven, we can make use of the electrophonocardiogram.
However, the safest way is to register simultaneously the
electrocardiogram at the three leads, or at least at two of
them. Einthoven has given a particularly elegant design for such
an instrument (1915, 1916) - two galvanometers one after the
other, each transferring its string registration on the same
plate. The firm of Carl Zeiss has carried out such a detailed
construction.
Thus Einthoven has added the discovery of the mechanism of the
electrocardiogram to the discovery of the true, individual
electrocardiogram. Sir Thomas Lewis was the first who realized
the importance of Einthoven's discovery and who followed his line
of thought. His elegant demonstration (1916) of the QRS-complex
in the electrocardiogram by means of an algebraic summation of
dextro- and laevogram confirmed the correctness of Einthoven's
interpretation, just as his demonstration of the «circus
movements» of the stimulation wave (1921) in cases of
auricular fibrillation proved conclusively the practical
importance of Einthoven's calculation of the «direction and
definite magnitude of the resultant potential variation».
The examination of literature in this field fully justifies the
statement that the importance of Einthoven's discovery of the
mechanism of the electrocardiogram has only been conclusively
proved by Sir Thomas Lewis's works previously mentioned.
Since Einthoven first described the details of the
electrocardiogram and more so after the publication in 1906 of
its appearance during the various heart diseases, a vast
literature in this field has accumulated over the years. All
these researches aim fundamentally to reveal the mechanism which
underlies the electrocardiogram. The question then arises: Which
facets of this mechanism have been brought to light? Let us
imagine that a heart model made from fresh heart muscles is
placed in a homogeneously conducting medium with leads connected
with a string galvanometer, and let us ask ourselves the
question: What should be put into this model so that it will give
the customary electrocardiogram? The answer now would be: (1) the
conduction system; (2) a conduction velocity in this system which
is several times greater than that in the heart muscle. Einthoven
was the first to point out the importance of the conduction
system. The importance of the conduction velocity has been shown
by Lewis.
The same mechanism governing the characteristics of the
electrocardiogram, also governs the characteristics of the
mechanical process during the heart beat. We should remember in
this connection that the mechanical process not only consists of
the succession of the stimulation of the separate parts of the
heart compartments, but also of the cooperation of the individual
parts of the heart wall which form the essential condition for
the mechanical effect in the individual ventricle or in the
individual auricle. A deficiency in this cooperation can, with
regard to the mechanical effect, be as fatal as a valvular
insufficiency. Today, the importance of the mechanism discovered
by Einthoven can easily be realized.
* Professor Einthoven being on a lecture tour
in the United states, and the other laureate of the year also
being unable to come to Stockholm, the usual ceremony on December
10 was cancelled.
** P.H. Kahn,
«Das Elektrokardiogramm», Ergeb. Physiol., 14
(1914) 1.
From Nobel Lectures, Physiology or Medicine 1922-1941, Elsevier Publishing Company, Amsterdam, 1965
Copyright © The Nobel Foundation 1924
MLA style: "Physiology or Medicine 1924 - Presentation Speech". Nobelprize.org. 23 May 2013 http://www.nobelprize.org/nobel_prizes/medicine/laureates/1924/press.html
