The Nobel Prize in Physiology or Medicine 1956
André F. Cournand, Werner Forssmann, Dickinson W. Richards
Presentation Speech by Professor G. Liljestrand, Secretary of the Nobel Committee for Physiology or Medicine of the Royal Caroline Institute
Your Majesties, Your Royal Highnesses,
Ladies and Gentlemen.
The heart is the sun of the microcosm formed by the human body,
as stated already by William Harvey in his monumental treatise on
the circulation of the blood. Its central role in both healthy
and pathologic states is well known and is illustrated, for
example, by the fact that cardiovascular diseases are at present
responsible for more deaths than any other group of diseases. It
is for essentially new contributions in this important field that
the Nobel Prize for Physiology or Medicine has been awarded this
year.
Two factors are decisive for the work of the heart. One is the
pressure conditions in its various chambers. The other is the
quantity of blood forced by its right side through the pulmonary
vessels to its left side which, in turn, transmits the blood to
all the parts of the body, to be returned once more to the right
atrium. Exact data regarding these two factors have long been
available through animal experiments. It has been possible to
measure the pressure, after introduction of catheters connected
to suitable recording instruments. The minute volume, i.e. the
blood flow per time unit, has been determined by measuring both
the oxygen uptake of the lungs, and the difference between the
oxygen content of the blood just leaving the lungs and that of
the oxygen-poorer blood flowing to them from the right side of
the heart.
As far as man is concerned, these methods were for a long time
only partly applicable. Thus, it was possible to record the
pressure in the peripheral arteries - and this is what is usually
meant when we speak of the blood pressure - as well as in the
superficial veins. These values reflect to some extent the
conditions in the left ventricle and the right atrium. But
measurements of the right ventricular pressure, which is of
essential importance for the work of the right side of the heart,
was impracticable. Similarly, it was possible, for determination
of the oxygen content, to take samples of the arterial blood, but
not of the mixed venous blood in the right side of the heart,
which gives the average value for the body as a whole. It was, in
fact, necessary to resort to indirect methods. These have yielded
valuable results, although they have somewhat undeservedly - as
is often the case - been overshadowed by the subsequent
conquests. One of the factors limiting the applicability of these
indirect methods was, however, that they required the active
cooperation of the experimental subject or patient, and this was
at times associated with difficulties or was altogether
unfeasible.
As late as 1928, there were good reasons for the statement in a
textbook that in man, one was «naturally» confined to
the use of the indirect methods. Consequently, it was highly
surprising when, already in the following year, Werner Forssmann
at the surgical clinic in Eberswalde was able to show - by
making, with the intrepidity of youth, by no means harmless
experiments on himself - that a narrow catheter could be advanced
from a cubital vein into the right atrium itself, a distance of
almost two-thirds of a metre. Obviously, this constituted a
remarkable advance. It was thereby demonstrated that, on
principle, the methods well known from animal experiments could
also be adapted for studies in man.
This was naturally of paramount importance for a study of
pathologic changes in the circulatory system, which could be
reproduced with difficulty, or not at all, in animal experiments.
It also opened up better opportunities for röntgenologic
examination of the right side of the heart and the pulmonary
vessels, after injection of contrast medium directly into these
organs. For this purpose as well, Forssmann made experiments on
himself. It must have required firm conviction of the value of
the method to induce self-experimentation of the kind carried out
by Forssmann. His later disappointment must have been all the
more bitter. It is true that the method was adopted in a few
places - in Prague and in Lisbon - but on the whole Forssmann was
not given the necessary support; he was, on the contrary,
subjected to criticism of such exaggerated severity that it
robbed him of any inclination to continue. This criticism was
based on an unsubstantiated belief in the danger of the
intervention, thus affording proof that - even in our enlightened
times - a valuable suggestion may remain unexploited on the
grounds of a preconceived opinion. A contributory cause in this
substance was presumably that Forssmann was working in a milieu
that did not clearly grasp the great value of his idea.
It was no mere coincidence that it was in New York that
Forssmann's contribution was once more brought to light. There,
André Cournand and Dickinson Richards had, with various
co-workers, made a thorough study of the circulation in different
pathologic conditions. Since their own experience had made them
familiar with the limitations of the current methods, they
realized the great desirability of being able to make direct
analyses of the conditions in the right side of the heart. It is,
however, characteristic that it was not until after several
year's preparations and much hesitation that the New York school
was able, in 1941, to publish a report of cardiac catheterization
in man. A few minor improvements were introduced, but the main
point was that a well-known research group at a distinguished
clinic had set their seal of approval on the method, which then
made its triumphant entry into the world of clinical
medicine.
Scientific progress often takes place by leaps and bounds, not
infrequently due to improvements in the technique which, in the
hands of skilful workers, may allow new fields of applicability.
Nor was success slow to occur in this case.
During World War II, as well as on earlier similar occasions,
secondary wound shock constituted a serious problem. This is a
state of circulatory failure which may appear several hours after
a severe injury. Cournand, Richards, and co-workers showed that,
although the causative mechanism varies, the essential feature is
a considerable decrease in the minute volume, due to a diminished
return of blood to the heart. This may, in turn, be a result of
blood loss, or it may also be due to insufficient contraction of
the smooth muscles in the blood vessel walls. A study of the
improvement brought about by blood transfusion could be made by
means of cardiac catheterization.
The turn then came to the acquired heart diseases, in which the
minute volume and the pressure conditions at rest and at work
were found to vary with the art and severity of the illness. The
observations illustrated the influence of the left side of the
heart on the right. They also provided a basis for evaluation of
the mutual role of changes in the heart muscle itself and in the
valvular apparatus. Although congenital heart disease occupies a
relatively modest place in the large complex of cardiac
disorders, it is by no means a rarity. It is generally a question
of developmental anomalies of widely divergent nature, such as
constriction or dilation of the great vessels given off from the
heart, of persisting patent communications between them, or of
defects in the ventricular or atrial septum. By taking blood
samples from different chambers of the heart and the great
vessels, by measuring the pressure at various sites and by the
refined röntgenological analysis, it has been possible to
make considerable diagnostic improvements and to obtain a better
conception of the conditions than that provided by earlier
techniques. It is, for example, possible to calculate the minute
volume in the systemic and the pulmonary circulations separately,
and thus to determine the quantity that is short-circuited from
one side of the heart to the other, usually from the left side to
the right. These investigations have, to an appreciable degree,
been instrumental in promoting the remarkable advances in heart
surgery made in recent time.
Respiration and circulation serve the common purpose of assuring
the gas exchange in the cells that is a prerequisite for the
maintenance of life. It is therefore entirely natural for an
intimate association to exist between them. Thus, a diminution in
the blood flow may produce increased respiration, and pathologic
changes in the respiratory apparatus may have an effect on the
heart. An example is the enlargement and, at times, failure of
the right ventricle which may appear in certain chronic pulmonary
diseases, among them silicosis, which is a threat in certain
occupations, and emphysema.
Cournand, Richards, and their group have shown that pulmonary
changes can, during slight work or even at rest, produce raised
pressure in the pulmonary artery, with increased demands on the
right ventricle as a result. They have also thoroughly studied
and elucidated the various factors responsible for these
disturbances, such as a reduction in the cross section of the
vascular bed, and decreased oxygen saturation of the arterial
blood owing to inadequate respiration, as well as impairment of
the actual membrane through which the oxygen must pass into the
blood.
These results, of which brief mention has been made, have been
the fruit of extensive investigations, implying the cooperation
of a large number of highly skilled research workers. Cournand
and Richards have, however, consistently been the pioneers and
the leaders. Moreover, the contributions made by the New York
school have been a source of inspiration in other parts of the
world and have, there as well, led to successful study of
countless problems.
Professors Cournand, Forssmann, and Richards. The Caroline Institute has decided to award this year's Nobel Prize in Physiology or Medicine to you jointly for your discoveries concerning cardiac catheterization and pathologic changes in the circulatory system. Your investigations have been performed at different times and in far distant parts of the world. Together, they signify the initiation and development of a new and important approach to our understanding of heart disease.
Professor Forssmann. As a young doctor you have had the courage to submit yourself to heart catheterization. As a result of this, a new method was born which since that time has proved to be of very great value. It has not only opened up new roads for the study of the physiology and the pathology of the heart and the lungs, it has also given the impetus for important researches on other organs. We are glad to be able to welcome you in this country where once your ancestors worked.
Professor Cournand and Professor Richards. The practical value of cardiac catheterization has been definitely proved by you and your co-workers. This method, combined with those already available before, has in your hands led to many important new observations, to diagnostic as well as therapeutic advances. The field is still in the process of exploration, and there is good reason to believe that rich harvests will also be reaped in the future. It is our hope that you will have the opportunity of continuing to take an active part in this development for many years to come.
Gentlemen. When Alfred Nobel
stipulated in his will
that one of his prizes should be awarded in the domain of
Physiology or Medicine, it was probably evidence of his
particular interest in what is often termed experimental
medicine. Your work is an outstanding example of the great
possibilities implied by the application of physiological methods
to clinical problems.
On behalf of the Caroline Institute I proffer you the hearty
congratulations of your colleagues on your brilliant
achievements.
I now have the honour of asking you to accept the Nobel Prize
from the hands of His Majesty the King.
From Nobel Lectures, Physiology or Medicine 1942-1962, Elsevier Publishing Company, Amsterdam, 1964
Copyright © The Nobel Foundation 1956
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