The Nobel Prize in Physiology or Medicine 1920
August Krogh
Schack
August Steenberg Krogh was born at Grenaa, Jutland, Denmark,
on November 15, 1874. He was the son of Viggo Krogh, shipbuilder,
and Marie, née Drechmann. Even as a schoolboy August
was much interested in the natural sciences and spent a great
deal of his time in experimentation. He was greatly stimulated by
his teacher and friend William Sörensen, D. Sc., who
especially advised him to take interest in physiology. After
having entered the University of Copenhagen in 1893 he started to study
medicine but soon devoted himself to zoology. In 1897 he began to
work in the Laboratory of Medical Physiology under the famous
Professor Christian Bohr. When he had passed his examination in
zoology, he became Bohr's assistant. In 1908 an Associate
Professorship in Zoophysiology was created for Krogh at the
University of Copenhagen, and eight years later this was changed
to an ordinary chair, which Krogh held till 1945, when he
retired. His work went on, however, in the private laboratory at
Gjentofte, erected for him with the aid of the Carlsberg and the
Scandinavian Insulin Foundations.
Krogh's scientific work embraces a number of different fields. As
a young student he started (1896) in his private room some
experiments on the hydrostatic mechanism of the Corethra larva,
the results of which were not published, however, until 1911. In
this connection he worked out methods for microscopical analyses
of the gas contained in the air bladders of the larvae and was
able to prove that these organs functioned like the diving tanks
of a submarine, their content being regulated until equilibrium
with the surrounding water was restored. In 1902 Krogh took part
in an expedition to Disko, North Greenland, where he studied the
CO2 tension and the oxygen content in the water of
springs, streams and the sea. This led to important results about
the role of the oceans in the regulation of the CO2 of
the atmosphere and also set out the principles of tonometric
measurement of dissolved gases which he later applied to
physiological problems (1904).
As Bohr's assistant Krogh became interested in problems connected
with the gas exchange of the living organism. At the age of 32
years (1906) he won the Seegen prize of the Austrian Academy of Sciences for a paper on the
expiration of free nitrogen from the body. Very careful
experiments with chrysalides, eggs and mice showed an extremely
slight production of gaseous nitrogen which might be accounted
for as being due to excretion of ammonia or, in the case of eggs,
as the setting free of physically dissolved nitrogen from the
body.
Krogh's dissertation (1903) contained a study of the gas exchange
in the frog. He found that, whereas the skin respiration was
relatively constant, great variations occurred with regard to
lung respiration. This part of the gas exchange was influenced
from the vagi. Krogh interpreted this result as another example
of the oxygen secretion that had been assumed by Bohr to take
place in the lungs. However, he soon began to doubt the
correctness of this conclusion - the observations might be
explained by a vasomotor action of the vagi - as well as the
whole doctrine of gas secretion in the lungs. Partly in
collaboration with his wife, Dr. Marie Krogh, he subjected the
whole question of the nature of the gas exchange in the lungs to
a new examination. For this purpose he constructed his well-known
microtonometer, where the tension equalization with blood takes
place against an air bubble of about 0.01 ml. The relative
surface therefore being very great, equilibrium is quickly
obtained, and, by the micromethods for gas analysis developed by
Krogh, the final composition of the air bubble could easily be
ascertained. The gas tension of the circulating arterial blood
was thus determined and compared to that in the lung alveoli as
obtained at the end of expiration. It turned out that the oxygen
tension was always higher in the alveolar air than in the
arterial blood, so that diffusion alone was sufficient to explain
the gas exchange (1910). These fundamental experiments were thus
opposed to the views of Bohr and of J. S. Haldane, but they were
later confirmed and extended by J. Barcroft in Cambridge and
others and are now generally accepted.
The results obtained shed new light on the whole complex of
mechanisms that enable the organism to answer the varying
«call for oxygen». A number of classical problems such
as the binding of gases in the blood, their transport by the
blood flow and the exchange of oxygen and CO2 in the
tissues attracted Krogh's attention, and to all of these he has
made important contributions.
In collaboration with Bohr and K. A. Hasselbalch the influence of
the CO2 tension on the oxyhemoglobin dissociation
curve of the blood was demonstrated. This investigation, which is
of fundamental importance for the modern conception of the
chemical combinations of the respiratory gases in the blood, was
made possible by the technique developed by Krogh. It became
extended by J. Christiansen, C. G. Douglas and J. S. Haldane's
finding that the oxygen tension also influences the
CO2 curve of the blood (1914).
Together with J. Lindhard, Krogh, adopted an idea that had been
introduced by A. Bornstein and developed their nitrous oxide
method for the determination of the general blood flow, which has
been of great importance for the further development in this
field. A considerable increase occurred during muscular work.
This was attributed to variations in the filling of the heart
during diastole. The supply of venous blood must therefore be
variable within wide limits and must during rest almost always be
inadequate to fill the ventricles. This conclusion was
strengthened by Krogh in an analysis of the underlying mechanism
1912), which also led to the conclusion that the portal system
acts as a general regulator of the pressure in the central veins
and thereby on the output of the heart. Another important result
of the determinations of the blood flow was the demonstration of
an increased utilization of the oxygen of the blood during
muscular work. Since the oxygen pressure of the resting muscles
was, as found by several authors, rather low, the higher
utilization must be explained by an increase in the diffusion
surface. Krogh came to this conclusion after he had made
experiments on the diffusion capacity of animal tissues, and
these considerations were the reason for his famous studies of
the capillaries during rest and work. As is well known, he thus
arrived at the conclusion that during muscular work new
capillaries which have been closed, are opened, thus enlarging
the surface from which the oxygen can diffuse. These
investigations resulted in the Nobel Prize in 1920. They were
greatly extended by Krogh in the following years, as shown in his
book The Anatomy and Physiology of the Capillaries (1922)
and several further publications. Other comprehensive
investigations on heavy muscular work were performed under the
auspices of the League of Nations by Krogh and his school (1934),
when a number of important problems were dealt with, such as heat
regulation, respiratory metabolism, influence of diet on the
capacity for work, blood sugar, lactic acid, training and
fatigue, kidney function.
In insects, as well as in vertebrates under standard conditions,
Krogh demonstrated a regular and constant influence on metabolism
of the surrounding temperature which could be expressed by
Arrhenius' formula. He also investigated the effect of certain
factors on the development in different animals. His rich
experience with regard to metabolism Krogh summarized in the
valuable monograph The Respiratory Exchange in Animals and
Man (1916). Later on (1920) with several collaborators he
made another important contribution to this series of problems by
establishing the fact that when fat is catabolized for muscular
work a loss of 11 % of the heat of combustion takes place, owing
to the waste when fats are converted to carbohydrates.
The work on the gas exchange during respiration was not confined
to vertebrates; Krogh also took up the analogous question of the
mode of function of the tracheal system of insects. Analyses of
the air from the tracheal tubes of the common grasshopper showed
comparatively low oxygen values while the CO2 output
was relatively small - probably it is given out directly through
the body surface to a great extent, whereas oxygen is taken up
only through the walls of the tracheae. A mechanical ventilation
of the tracheae is made difficult by their structure - in many
cases no respiratory movements occur - but experiments by Krogh
(1920) showed that gas diffusion alone is sufficient to explain
the oxygen uptake. In the course of his last unpublished studies
on locusts Krogh found that during flight, when there is an
enormously increased oxygen uptake in the wing muscles, a special
arrangement enables a mechanical ventilation of their tracheae to
occur. In his book The Comparative Physiology of Respiratory
Mechanisms (1940) Krogh has given a fascinating and lucid
description of many different ways in which the demand for oxygen
is met in the animal kingdom.
For several years Krogh and his school have been studying the
exchange of water and inorganic ions through the surface of
living cells and membranes, partly with the aid of isotopes as
indicators. The many facts observed in this work have been
reviewed by Krogh in his monograph Osmotic Regulations in
Aquatic Animals (1937) and in a Croonian lecture
(1946).
Mention should also be made of his numerous additions to
physiological techniques. His recording spirometer is used in
many hospitals, his bicycle ergometer is an appreciated working
machine, his precision pipettes, respiration apparatus, improved
methods for gas analysis and many other inventions bear witness
to his constructive skill.
This brief survey is far from complete and is only intended to
cover the main lines of Krogh's scientific activity. It
illustrates not only his broad interests and unusual ability to
take up fundamental problems and derive essential results
everywhere. By his own work he has emphasized the quantitative
aspect in physiological research, through his numerous pupils he
has promoted such ideas into different fields of medicine.
Krogh was given Honorary Doctorates by the Universities of
Edinburgh,
Budapest, Lund,
Harvard,
Göttingen, Oslo, and Oxford. He was made a member of the
Academy of Sciences, Denmark (1916) and became foreign member of
many other academies and learned societies, among them The Royal
Society, London (1937). The same year, he was awarded the
Baly medal of the Royal College of Physicians, London.
In 1905, Krogh married Birte Marie Jörgensen, a medical
student, who obtained her M. D. degree on an important paper,
entitled Luftdiffusionen gennem Menneskets Lunger, 1914
(The Diffusion of Gases through the Lungs of Man, J.
Physiol., 1915) in a field where she had been engaged with
her husband. She died in 1943. There were four children, one son
who became Prosector of Anatomy at the University of Aarhus - a
post he held until his untimely death - and three daughters. The
youngest of them is a well-known physiologist in U.S.A., having
above all performed important researches in zoophysiology, mainly
in collaboration with her former husband, K. Schmidt-Nielsen.
Dr Krogh died in Copenhagen on September 13, 1949.
From Nobel Lectures, Physiology or Medicine 1901-1921, Elsevier Publishing Company, Amsterdam, 1967
This autobiography/biography was written at the time of the award and first published in the book series Les Prix Nobel. It was later edited and republished in Nobel Lectures. To cite this document, always state the source as shown above.
Copyright © The Nobel Foundation 1920
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