Editorial
Pokrovskii M.V., Avtina T.V., Zakharova E.V., Belousova Yulia V. Oswald Schmiedeberg – the
“father” of experimental pharmacology. Research Result: Pharmacology and Clinical
Pharmacology. 2017;3(4):3-19.
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December. 2017. 3(4). Research Result: Pharmacology and Clinical Pharmacology rrpharmacology.ru
EDITORIAL
UDC: 615:378 DOI: 10.18413/2313-8971-2017-3-4-3-19
Mikhail V. Pokrovskii1
Tatyana V. Avtina T.
Elena V. Zakharova
Yulia. V. Belousova
OSWALD SCHMIEDEBERG –THE “FATHER” OF
EXPERIMENTAL PHARMACOLOGY
Belgorod State National Research University, 85 Pobedy St., Belgorod, 308015 Russia
Corresponding author, 1e-mail: pokrovskii@bsu.edu.ru
“Our tribute to the memory of the Teachers
and those who were pioneers of pharmacology
is an invaluable gift to our descendants”
Abstract
Biography. Oswald Schmiedeberg (1838-1921) was a son of a bailiff and a maid of
honour, the eldest of the six children in the family. He was born and educated in the
Russian Empire.
Scientific activity. All his life he was completely devoted to science, making
experimental pharmacology an independent scientific discipline, and was able to bring it
to the international level. O. Schmiedeberg studied the action of muscarine and nicotine,
digitoxin, hypnotics and analeptics. He was the first to introduce the concept of
―pharmacodynamics‖ and ―pharmacokinetics‖ of a drug. With his participation, the
world‘s first pharmacological journal was founded, which is still published today.
Science school. Working for many years at the University of Strasbourg, Schmiedeberg
managed to educate about 120 students – professors from 20 countries of the world,
many of whom later founded experimental pharmacology in their countries, for
example, Abel in the USA, and N.P. Kravkov in Russia. Scientific activity of
Schmiedeberg influenced scholars of his time and for generations to come, creating the
preconditions for new high-profile discoveries and even for receiving Nobel prizes. But
Oswald Schmiedeberg failed to obtain this high award himself, though he had been
nominated 14 times.
Biography
Oswald Johann Ernst Schmiedeberg
(Figure 1) was born on 29.09.1838 (on
11.10.1838 New Style) in Gut-Laizane, in
Courland (Laidze parish, Talsi municipality,
Latvia), which was at that time part of the
Russian Empire.
His father, Wilhelm Ludwig Schmiedeberg
was born in 1809 in Vindau (Latvia), a son of
Johann Ernst (a mechanic in Libau) and
Gertrude Borchet. He worked as a bailiff in
Leidzen, later took charge of the forestry in
Permisküla, and Paggar (Estonia), died in 1878
in Dorpat. The mother of O. Schmiedeberg,
Anna Lucy Bernard, was born in Lausanne
(Switzerland) in 1813, a daughter of Johann
Bernard, a watchmaker in Lausanne. She
worked as a maid of honor and died in 1871.
His brother, Johann Julius Rudolf, was born in
1840, worked as a forester in Estonia and was
Rus.
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December. 2017. 3(4). Research Result: Pharmacology and Clinical Pharmacology rrpharmacology.ru
never married. Oswald Schmiedeberg was the eldest of the six siblings [1, 2].
Fig. 1. Oswald Schmiedeberg [3]
After finishing a primary school in
Permisküla, Schmiedeberg studied at a district
school of Dorpat (today Tartu, Estonia) from
1852 to 1854. In 1855 he studied at the
gymnasium in Dorpat, which he successfully
finished in 1859, after which he entered the
Medical Faculty of the University of Dorpat,
where he was a student till 1866. The Imperial
University of Dorpat (The Imperial University
of Yuryev from 1893 to 1918) was one of the
oldest universities in the imperial Russia;
nowadays it is The University of Tartu in
Estonia (Figure 2) [4, 5, 6].
Schmiedeberg studied at the university at
one of the best periods of the Medical Faculty
of the University of Dorpat, which was
connected with the hey day of Enlightenment in
Russia in the second half of the 19th century. In
the 1860s, when in all spheres of scientific
activity there was a definite change for the
better, a system of freelance university lecturers
(privat-docents) started to develop at the
Medical Faculty, where only after 1863, young
scientists (privat-docents) began to work on a
constant basis. All this, undoubtedly, was due
to the Enlightenment process in Russia at that
period. The very development of the system of
freelance university lecturers (privat-docents)
at Dorpat Medical Faculty proves that at that
Pokrovskii M.V., Avtina T.V., Zakharova E.V., Belousova Yulia V. Oswald Schmiedeberg – the
“father” of experimental pharmacology. Research Result: Pharmacology and Clinical
Pharmacology. 2017;3(4):3-19.
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December. 2017. 3(4). Research Result: Pharmacology and Clinical Pharmacology rrpharmacology.ru
time it was in a flourishing condition, there
were those who could teach and those who
wanted to study [2].
Fig 2. The Imperial University of Dorpat, 1860 [7]
After graduating from the University of
Dorpat in 1866, O. Schmiedberg defended his
doctoral thesis On Quantitative Determination
of Chloroform in Blood and Its Behavior
Towards the Former (“Ueber die quantitative
Bestimmung des Chloroforms im Blute u. Sein
Verhalten gegen dasselbe”) under the
supervision of Professor Rudolf Buchheim [8,
9, 10, 11]. The title page of the dissertation of
the scientist can be seen in Fig. 3.
Rudolf Buchheim was elected by the
Council of Dorpat University to the
Department of Pharmacology on December 30,
1846, and from October 1849 to 1867, he was
an ordinary professor at that department. His
fruitful professorship and his constant desire to
recognize pharmacology as a science
independent of therapy, putting it on the
experimental research basis, made him so
famous that foreign universities such as The
University of Breslau, The University of Bonn
and The University of Giessen tried to hire him.
R. Buchheim was the first scientist who put
pharmacology on sound scientific grounds, and
the manual that he compiled included for the
first time the description of the physiological
effect of agents, on which their therapeutic
application was based. The vision of Buchheim
served as the cornerstone of modern
pharmacology. One of the important
achievements in Buchheim‘s scientific life is
considered to have been the education of his
follower in science, one of the greatest
scientists – Oswald Schmiedeberg [2, 13].
Pokrovskii M.V., Avtina T.V., Zakharova E.V., Belousova Yulia V. Oswald Schmiedeberg – the
“father” of experimental pharmacology. Research Result: Pharmacology and Clinical
Pharmacology. 2017;3(4):3-19.
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December. 2017. 3(4). Research Result: Pharmacology and Clinical Pharmacology rrpharmacology.ru
Fig 3. Title page of the thesis by O. Schmiedeberg [12]
While working at Dorpat University,
Schmiedeberg actively cooperated in his
research with outstanding scientists of that
time: a biochemist Karl Schmidt (1822-1894),
anatomist Friedrich Heinrich Bidder (1810-
1894), physiologist Karl Wilhelm von Kupffer
(1829-1902), etc.
Karl Ernst Heinrich Schmidt was a Russian
chemist of German-Baltic descent, a professor
at the University of Dorpat, and a
corresponding member of the Petersburg
Academy of Sciences (1873). He supervised a
degree project of Wilhelm Ostwald, a Nobel
laureate in Chemistry, when the latter was
seeking a Doctor of Philosophy degree [2, 14].
Georg Friedrich Carl Heinrich Bidder was
a Russian physiologist and anatomist of
German-Baltic descent, Professor and Rector of
the Imperial University of Dorpat (1857-1864),
acorresponding member (1857) and an
honorary member (1884) of St. Petersburg
Academy of Sciences. In 1869, F.H. Bidder
retired as Professor Emeritus [15, 16].
Carl Schmidt and Friedrich Bidder were
the first scientists who managed to dispel the
doubts of Henry Bence Jones, who had
Pokrovskii M.V., Avtina T.V., Zakharova E.V., Belousova Yulia V. Oswald Schmiedeberg – the
“father” of experimental pharmacology. Research Result: Pharmacology and Clinical
Pharmacology. 2017;3(4):3-19.
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December. 2017. 3(4). Research Result: Pharmacology and Clinical Pharmacology rrpharmacology.ru
published an article in The Lancet magazine in
1850, in which he wrote: ―The gastric juice is a
strongly acidic liquid secreted by the stomach
... . Which acid still remains unknown. Salt,
phosphoric, acetic, lactic and butyric acids are
said to be present in gastric juice‖ [17]. In
1852, F. Bidder and C. Schmidt published the
book Die Verdauungssaefte und der
Stoffwechsel (Digestive Juices and
Metabolism), in which they presented the
results of a quantitative analysis of gastric juice
collected from various species of live animals,
confirming the fact that the stomach normally
secretes hydrochloric acid [15].
Karl Wilhelm Kupfer, a German anatomist,
histologist and embryologist, was a student of
Friedrich Bidder, a prosector and an
extraordinary professor at the University of
Dorpat (1856–1866). His studies, conducted
jointly with Bidder, were on the structure of the
spinal cord. In honor of Kupfer, specialized
liver macrophages the main function of which
is capturing and processing old nonfunctional
blood cells were called Kupffer cells [18].
After defending his dissertation in 1866, O.
Schmiedberg became Assistant Professor to R.
Buchheim at the Pharmacological Institute, and
in 1867 he received the title of Privat-docent.
When Buchheim left Dorpat after getting an
invitation from the University of Giessen,
Schmiedeberg was asked to give lectures on
pharmacology and dietics. In 1868, he was
appointed Full-time Associate Professor, and in
1869 - an Extraordinary Professor of
Pharmacology, Dietics and History of
Medicine. After being appointed an
Extraordinary Professor, Schmiedeber was
appointed Director of the Pharmacological
Institute, which he had held since the departure
of Buchheim.
Together with the renowned scientists of
the University of Dorpat, Schmiedeberg made a
number of discoveries. Before 1870, his studies
on physiological chemistry had led to the
discovery of sulfuric acid in the urine of cats
and dogs. Together with Ernest Bergman, he
conducted research on the poison of rotting
substances and discovered sepsin in form of its
sulfuric acid salt. Together with Dr. Richard
Koppe, Schmiedeberg in 1868 studied the
composition of the fly agaric (Agaricus
muscarius), which led to the isolation of
muscarin, the properties of which were studied
in detail by both authors. Over that time, ten
scientific dissertations were completed under
the supervision by O. Schmiedeberg [2, 5].
In 1870, Schmiedeberg continued his
education in Germany, in Leipzig. He spent a
whole year at Leipzig University, working
together with the outstanding physiologist Karl
Friedrich Wilhelm Ludwig (1816-1895). O.
Schmiedberg successfully used the kymograph
(device for recording blood pressure) invented
by K. Ludwig in his scientific experiments and
reasonably considered K. Ludwig one of his
scientific teachers [19]. Fig. 4 shows a
kymogram obtained on smoked paper.
Fig. 4. Example of kymogram on smoked paper [20]
Pokrovskii M.V., Avtina T.V., Zakharova E.V., Belousova Yulia V. Oswald Schmiedeberg – the
“father” of experimental pharmacology. Research Result: Pharmacology and Clinical
Pharmacology. 2017;3(4):3-19.
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December. 2017. 3(4). Research Result: Pharmacology and Clinical Pharmacology rrpharmacology.ru
In 1871, Oswald Schmiedeberg became
Full Professor of Pharmacology, Dietics and
History of Medicine at the University of
Dorpat. From 1871 to 1872, Schmiedeberg
visited Bern and Kцnigsberg (Prussia), and in
1872, Schmiedeberg resigned from the
University of Dorpat after accepting a position
at the just-founded University of Strasbourg,
where later he was to get engaged in research
and teaching for the next 46 years, started his
own scientific school and was the Director of
the Pharmacological Institute [2].
After arriving at the University of
Strasbourg, his scientific laboratory was a very
small room in a hospital at Place de l'Hфpital.
Along with promoting research in experimental
pharmacology, in 1887 the University
administration assigned a new spacious
building for the laboratory, the building having
been designed by Schmiedeberg himself, in
cooperation with the architect Otto Warth
(1845-1918). Schmiedeberg‘s office and
personal laboratory were on the second floor,
the laboratory at the corner with the balcony,
the office immediately to the left with the bow
window (Figure 5) [21, 22].
The University of Strasbourg was one of
the most prestigious and best schools at the
time. Along with Schmiedeberg, there worked
a number of prominent scientists. Among them
was anatomist Heinrich Wilhelm Waldeyer
(1836-1921), who was engaged in anatomical,
histological, comparative-anatomical and
embryological studies. In 1884, he published a
paper in which he gave a detailed description of
the embryogenesis, structure and functional
significance of the pharyngeal lymphoid tissue
(Pirogov-Waldeyer’s ring). In 1888, for the
first time he used the term ―chromosome‖, was
one of the first supporters of Cajal‘s neural
theory and suggested the term ―neuron‖ [23].
Other famous scholars were Felix Hoppe-
Seyler (1825-1895), one of the founders of the
Department of Biochemistry and the founder of
the journal of physiological chemistry and
pathologist Friedrich Daniel von
Recklinghausen (1833-1910), whose research
papers were on neurofibromatosis, parathyroid
osteodystrophy and fibrous ostitis (these
diseases, as well as a number of other
pathological processes were later called by his
name), and who studied rickets and
osteomalacies, which later became classical.
Schmiedeberg was the youngest among
colleague scientists.
Fig. 5 The Institute of Pharmacology in Strassburg,1877 [21]
Pokrovskii M.V., Avtina T.V., Zakharova E.V., Belousova Yulia V. Oswald Schmiedeberg – the
“father” of experimental pharmacology. Research Result: Pharmacology and Clinical
Pharmacology. 2017;3(4):3-19.
9
December. 2017. 3(4). Research Result: Pharmacology and Clinical Pharmacology rrpharmacology.ru
In the period from 1918 to 1919, O.
Schmiedeberg moved to Baden-Baden, where
he lived till his death. His friend in Baden-
Baden was B. Naunyn. They were neighbors
and often would take a walk along a forest road
in Baden-Baden, which is now called Schriever
Lane [24].
His view of pharmacology as an
independent exact science, O. Schmiedeberg
laid in the third edition of his work
Fundamentals of Pharmacology, for which he
tried to provide a rational basis in contrast to
purely subjective empiricism [15].
Schmiedeberg‘s Alma mater, The
University of Dorpat, after the fall of the
Russian Empire in 1918 was intervened by the
Germans. Due to an increase of Russophobia
and the First World War, the University faculty
members were evacuated to Voronezh, where
they made up the basis for Voronezh State
University [21, 22, 25].
Oswald Schmiedeberg died on
12.07.1921, at the age of 83.
Scientific activity
The vast knowledge acquired when
cooperating with many professors in the field
of medicine and chemistry allowed O.
Schmiedeberg to make a number of
discoveries.
Muscarine, nicotine. In 1869, in the
monograph by Oswald Schmiedeberg and
paramedic Robert Koppe, there appeared for
the first time an article about muscarin as a
toxic alkaloid extracted from fly-agarics
(Agaricus muscarius L.) [26]. When working
together, the scientists isolated pure poison
from fly-agarics picked in the vicinity of
Dorpat and described its pharmacological
effects, named them muscarinic and proved that
the poison possessed an antagonistic action
towards atropine. Antagonism manifested by
atropine against muscarinic receptors was a
prototype of competitive antagonism. The work
in question was of fundamental importance for
pharmacology and medicine as a whole and
resulted in the discovery of the chemical
transfer of impulse in synapses by Otto Loewi
(1873-1961). As O.Shmideberg and R. Koppe
wrote: ―These effects not only are of high
scientific, but also practical interest, since their
study has led to the discovery of a
physiological antidote to the poison of fly-
agaric, which will help avoid the life-
threatening consequences of accidental
poisoning with this widespread species of
mushrooms. Thus, poisoning can probably be
completely avoided.
Soon after studying the pharmacological
affects of muscarine, O. Schmiedeberg began
to study another pharmacological agent –
nicotine. The Professor was the first in Dorpat
who got interested in this issue, and he further
continued his studies in Karl Ludwig‘s
laboratory in Leipzig. Schmiedeberg proved
that nicotine suppressed the inhibitory effect of
the vagus nerve on the heart and conlcluded
that this happened due to ganglionic blockade.
That theory was examined thoroughly and was
later confirmed in the teachings by John
Newport Langley (1852-1925) when studying
the autonomic nervous system [27, 28].
About 150 years have passed since the
discovery of the pharmacological effects of
muscarin and nicotine, but modern textbooks
on pharmacology still describe vegetotrophic
agents basing on Schmiedeberg‘s
understanding of M- and N-cholinergic
receptors, their agonists and antagonists.
Digitalis. One of the most famous
works by O. Schmiedeberg and the main
direction of his research is rightly considered to
have been the study of digitalis, namely
alkaloids isolated from this flower. Despite the
fact that there was little information about the
medicinal properties of digitalis at that time,
this topic caused a lot of arguments and
controversy. It was O. Schmiedeberg who
managed to work out many questions.
In 1874, when Schmiedeberg returned
from France, he for the first time isolated a
separate substance from the collected red
flowers of the digitalis and called it digitoxin.
This substance was proved to have a serious
effect on the activity of the cardiovascular
system. His colleague, Robert Koppe, agreed to
conduct an experiment to study the
pharmacological effects of digitalis on his own
body. During the experiment, R. Koppe
recorded the pulse on his wrist (Figure 6).
Ingestion of 3.5 mg of digitoxin led to serious
poisoning, as well as to the side effects in form
of arrhythmia (Pulsus bigeminus).
Pokrovskii M.V., Avtina T.V., Zakharova E.V., Belousova Yulia V. Oswald Schmiedeberg – the
“father” of experimental pharmacology. Research Result: Pharmacology and Clinical
Pharmacology. 2017;3(4):3-19.