JNEPHROL 2009 ; 22 (S14): S80 - S85
ON HISTORY OF MEDICINE
www.sin-italy.org/jnonline – www.jnephrol.com
Tadeusz Reichstein: from description of
coffee aroma to discoveries of cortisone
and aldosterone
Boleslaw Rutkowski1, Janusz Ostrowski2
Abstract
Tadeusz Reichstein was born in Wloclawek (Poland)
into a Polish-Jewish family. His family emigrated to
Switzerland, and he was educated in the Technical
University of Zurich, becoming an engineer of chemistry. Thus he started his scientific career, firstly in
Zurich and later in Basel. In his very busy life, he developed a method of vitamin C synthesis enabling
industrial production of this important compound.
Later, Reichstein isolated and synthesized such
important adrenocortical hormones as cortisone,
desoxycorticosterone and aldosterone. He received
several awards but the most important was a Nobel
Prize in Physiology or Medicine (1950). Reichstein
spent the last years of his life in his own botanical
garden and laboratory working on fern cytogenetics and the relations between different species of
this archaic plant. Despite extraordinary and still
valuable scientific achievements, he was always a
very modest man with a humanistic attitude.
Key words: Discovery of aldosterone, Discovery of
cortisone, Tadeusz Reichstein
Introduction
There are not many scientists of Polish origin who are internationally recognized. Nicolaus Copernicus, the famous
astronomer who described the existence of the heliocentric
S80
Department of Nephrology, Transplantation and Internal
Medicine, Medical University of Gdansk, Gdansk - Poland
2
Division of Nephrology, Regional Specialist Hospital,
Wloclawek - Poland
1
system in the 15th-16th century is one of the widely known
exceptions. Another person known throughout the world is
Maria Skłodowska-Curie, a Nobel Prize winner in physics
in 1903 together with her husband Peter Curie for their studies of the radioactivity. Eight years later in 1911, she was
awarded a second Nobel Prize, this time in chemistry for
the discovery of such substances as radium and polonium.
On the other hand, there are persons unknown in the history of our scientific elites who are really worth remembering
because their efforts are exceptional and important for all
of mankind. This applies to the life and achievements of Tadeusz Reichstein, a great scientist and Nobel Prize winner,
but on the other hand also a very modest man.
Tadeusz Reichstein: biography and
scientific achievements
Tadeusz Reichstein was born in Wloclawek, a city located in the Cuiavian region of Poland, on July 20th, 1897.
His father, Israel (Izydor) Reichstein, was a well-educated
engineer mainly involved in the production and trade of
sugar. His mother was Gustawa Brokman from a wellsituated (saw-mill owners) Polish-Jewish family. In their
family, Polish patriotic traditions were always celebrated
with great care. Tadeusz was given his name in memory of the Polish-American hero Tadeusz Kosciuszko. His
brother Adam was named in memory of the internationally
recognized Polish poet Adam Mickiewicz (1, 2). One has
to remember that it was a time when Poland did not exist
on the map of Europe because of its partition among 3
powerful neighbors – Austria, Prussia and Russia – at the
end of the 18th century.
His childhood and first steps in basic education, Reich-
JNEPHROL 2009 ; 22 (S14): S80 - S85
stein spent in Wloclawek. In 1906-1907 his family moved
to Switzerland where he later spent the rest of his life.
Before establishing himself in Zurich, Reichstein was educated in Landserzierungsheim in Jena (Prussia) at a very
well known primary school for children from well-situated
families. The level of education was very high but unfortunately connected with a typical Prussian regime. Later Tadeusz completed his education at home and in the Ober-
realschule in Zurich. During the period 1916-1920, he
studied in the Faculty of Chemistry Technical University in
Zurich. After finishing his studies, Reichstein worked briefly in winery researching wine quality chemical markers,
and in a small company producing electric flashlights. At
last he got a position as assistant in the Institute of Organic Chemistry in his own Technical University in Zurich.
The head of this institute was Prof. Herman Staudinger,
TABLE I
MAIN SUBJECTS OF RESEARCH DURING TADEUSZ REICHSTEIN’S LONG SCIENTIFIC CAREER
Number of
publications
Subject (references)
Main place and time of studies
Main results of these studies
Studies of coffee aroma
(4-8)
1921-1925
Institute of Organic Chemistry,
Federal Technical University, Zurich
(head: Prof. Hermann Staudinger)
1935-1931
Frebon Company, Albisrieden
15
Isolation and description of 60 (out of
600) chemical components of coffee
aroma (furans and pyrroles)
Studies of vitamin C
synthesis
(9-12)
1932-1937
Institute of Organic Chemistry,
Federal Technical University, Zurich
(head: Prof. Leopold Ruzicka)
35
Elaboration of the original method
of vitamin C synthesis, enabling its
industrial production
Studies of adrenal cortex
hormones
(13-22)
1936-1938
Institute of Organic Chemistry,
Technical University, Zurich (head:
Prof. Leopold Ruzicka)
1938-1960
Institute of Pharmaceutical Chemistry (later Institute of Organic Chemistry, University of Basel (head:
Prof. Tadeusz Reichstein)
173
Isolation, description and synthesis of
30 different steroids, 6 of them biologically active (e.g., cortisone, desoxycorticosterone, aldosterone)
Studies of chemistry
of cardiac glycosides
(strophanthin, digitonine,
bufogenin,
digoxigenin, etc)
(23-25)
1940-1967
Institute of Pharmaceutical (later
Institute of Organic Chemistry),
University of Basel (head: Prof.
Tadeusz Reichstein)
1967-1987 Personal botanical
garden, and in laboratory as retired
scientist, Basel
218
Description of the action and relationship of many plant compounds active
as cardiac glycosides
Studies of fern
cytogenetics, relations
and hybridization
(26-29)
1957-1995
Personal botanical garden, and
in laboratory, Basel
85
Description of many new fern hybrids
S81
Rutkowski and Ostrowski: T. Reichstein - discovery of cortisone and aldosterone
Fig.1 - Two books commemorating Prof. Tadeusz Reichstein (1897-1996) edited in Poland.
who remembered his talented student. Under the direction of Staudinger, they started studies on the substances
involved in coffee aroma. These studies lasted almost 10
years, and 60 out of 600 compounds were isolated and
described by this team. The aim of these studies was very
practical and was supported by the Swiss Trade Guild,
connected with the program of artificial coffee production.
They did not achieve their aim. Nevertheless Reichstein
became an expert in the isolation of the heterocyclic compounds furans and pyrroles (3-8). One has to remember
that his first mentor, Prof. Staudinger, received the Noble
Prize in 1953 and is known as the father of polymer chemistry. During this time he completed his doctoral thesis,
and in 1922 became a doctor of technical sciences. The
further scientific career of Reichstein is shown in Table I.
He was lucky enough to also meet another great scientist,
Prof. Leopold Ruzicka. Reichstein worked with him for the
next 8 years as an assistant lecturer after accomplishing
his habilitation in 1930, and later as a full professor (in
1934). During this time, Reichstein was able to elaborate
S82
together with his team a new method of vitamin C synthesis enabling cheap industrial production of this very important biological compound (10-12). Simultaneously he
started studies connected with the isolation of chemical
compounds with biological activity from adrenocortical
extracts. Reichstein identified, worked out the structure of and synthesized more then 30 substances. Six of
them appeared to be biologically active. These studies
were supported by Organon Company, and because of
a specific conflict of interest inside the Institute of Organic Chemistry in Zurich. Ruzicka himself was involved in
the studies on sex hormones, mainly androgens, which
were supported by another great pharmaceutical company - Ciba. As a result of these studies, Ruzicka was
awarded with a Nobel Prize in 1937 for the description
of testosterone. Nevertheless, this competition between
Ciba and Organon Company was the main reason that
in 1938 Reichstein left Zurich and became director of the
Institute of Pharmaceutical Chemistry (1938) and later Institute of Organic Chemistry in the University of Basel. He
JNEPHROL 2009 ; 22 (S14): S80 - S85
Edward Kendall
Tadeusz Reichstein
Philip Hench
Fig. 2 - Nobel Prize diploma of Tadeusz Reichstein and other scientists (Edward Kendall and Philip Hench) involved in the isolation, synthesis and first clinical use of cortisone.
spent the next 20 years there (Fig. 1). Initially, Reichstein
continued his studies into the isolation of adrenocortical
hormones (13-18). These studies were very successful,
and Reichstein was awarded a Nobel Prize, together with
2 other scientists – Edward Kendall and Philip Hench from
the Mayo Clinic, United States (Fig. 2). This was mainly
for their work on corticosterone. These discoveries enabled the beginning of the era of the wide use of steroids
in different diseases, including many nephropathies. Reichstein synthesized and later isolated 2 other important
hormones: desoxycorticosterone (1937-1938) and aldosterone (1953) (Fig. 3) (19-22). He also tried to find a natural source of steroidal compounds. These studies were
based in his own private botanical garden and the Institute’s laboratories. He isolated and described several com-
pounds from natural plants active as cardiac glycosides
(23-25). In 1967, Reichstein retired, but he began a new
scientific passion. He started studies on the cytogenetic
properties and relations of ferns – one of the most archaic
plants. Reichstein – a genial chemist in the last decades
of his life – became an internationally recognized expert
in this branch of botanics (26, 27). These studies resulted
in the description of many new fern hybrids (28, 29). Just
how involved he was in these discoveries can be seen in
an interview he gave to a Swiss journal on the occasion
of his 90 birthday. To the question “What may we offer you
on your birthday?” he replied: “I don’t really know … But
… I need another two, three years to finish my studies in
the relationship between fern species.” Reichstein died
on the 1st of August, 1996, and was buried in the Israelitic
S83
Rutkowski and Ostrowski: T. Reichstein - discovery of cortisone and aldosterone
Summary
In summarizing the very active life and achievements of an
extraordinary personality, one has to realize that his achievements may fill not one but several biographies. Additionally, Reichstein’s studies are still important both from the
theoretical and practical point of view (30-32). He published
over 730 papers, taught 150 doctors, developed several biologically active compounds, was recognized as an honorary
member by 35 scientific societies worldwide and received
honorary doctorates from 7 universities (Sorbonne, London,
Leeds, Zurich, Geneva, Abidjan and the Medical University
in Gdansk). His biography was fully covered in Poland by Dr
S. Sterkowicz in 2 separate monographs shown in Figure 1.
Finally, it is worth to recording what Reichstein himself thought about the relationship between his favorites branches of
science – chemistry and biophysics - and life:
“There was a time, when scientists believed that the phenomenon of life is possible to describe using chemical and
physical principles. I never agreed with these theses. Chemistry has to know its own limits.” (1)
Fig. 3 - Chemical structures of the 3 most important corticoid
hormones isolated and synthesized by Tadeusz Reichstein.
Financial support: No financial support.
Conflict of interest statement: None declared.
Community Cemetery in Basel. Once again it is necessary
to underline that he remembered always his Polish-Jewish
roots, which he expressed himself in the following sentence: “I feel Swiss of Polish-Jewish origin. I am a long-term
member of the Jewish Community in Basel, nevertheless
quite rarely do I visit the synagogue.”(1)
References
1.
2.
3.
S84
Sterkowicz S. Tadeusz Reichstein: life and scientific activity.
Wloclawek: Expol; 1995.
Sterkowicz S. Tadeusz Reichstein: winner of Nobel prize in
physiology and medicine. , Wloclawek: LEGA; 2005.
Reichstein T. Beitrag zur qualitativen organisch-chemischen
Analyse. II. Antrachion-beta-carbonsäure-chlorid als Reagens
Address for correspondence:
Boleslaw Rutkowski
Department of Nephrology, Transplantation and Internal
Medicine
Medical University of Gdansk
Debinki 7
80-211 Gdansk, Poland
[email protected]
4.
5.
6.
auf Alkohole etc. Helvetica Chimica Acta. 1927;10: 387-393.
Reichstein T, Zschokke Z, Georg A. Aldehydsyntesen in der
Furan-Reihe. II. Synthese der Elsholtziasäure und des Elsholtzia-ketons. Helvetica Chimica Acta. 1931;14:1277-1283.
Reichstein T, Grüssner A, Zschokke H. Aldehydsynthesen in
der Furan-Reihe III Zweikernige Furankörper, Difuryl und Difurylmethan. Helvetica Chimica Acta. 1932;15:1066-1074.
Reichstein T, Staudinger H. Das Aroma des gerösteten Kaf-
JNEPHROL 2009 ; 22 (S14): S80 - S85
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
fees. Experientia. 1950;6:280-286.
Reichstein T, Staudinger H. Über das Kaffeearoma. Angewandte Chemie. 1950;62:292-300.
Reichstein T, Staudinger H. Das Kaffeearoma. Ciba Zeitschrift.
1951;127:4692-4699.
Reichstein T, Grüssner A. Die Synthese der D-Ascorbinsäure (d-Form des C Vitamins). Helvetica Chimica Acta.
1933;16:561-570.
Reichstein T, Grüssner A, Oppenauer R. Syntese der dund 1-Ascorbinsäure (C-Vitamin). Helvetica Chimica Acta.
1933;16:1019-1028.
Reichstein T, Grüssner A, Oppenauer R. Synthesis of d-and
1-ascorbic acid (vitamin C). Nature. 1933;132:280-291.
Reichstein T, Grüssner A, Oppenauer R. Synthese der Ascorbinsäure und verwandter Verbindungen nach der Oson-BlausäureMethode. Helvetica Chimica Acta. 1934;17:510-517.
Reichstein T. Über Cortin, das Hormon der Nebennierenrinde. Helvetica Chimica Acta. 1936;19:29-37.
Reichstein T. Adrenosteron. Helvetica Chimica Acta.
1936;19:401-408.
Reichstein T, Verzar F, Laszt L. Activity of corticosterone in
the glucose test in rats. Nature. 1937;139:331-339.
Steiger M, Reichstein T. Chemical structure of corticosterone. Nature. 1938;141:202-210.
Reichstein T, von Euw J. Isolierung der Substanzen Q (desoxycorticosteron) und R. sowie weiterer Stoffe. Helvetica Chimica
Acta. 1938; 21:1197-1205.
Reichstein T, Shoppee C. The hormones of the adrenal cortex. Vitam Horm. 1943;18:243-251.
Reichstein T, Reich H. The chemistry of the steroids. Annales
Revue of Biochem. 1946;15:155-166.
Simpson S, Tait J, Wettstein A, et al. Konstitution des Aldosterons des neuen Mineralcorticoids. Experientia.
1954;10:132-139.
Simpson SA, Tait JF, Wettstein A, et al. Konstitution des
aldosterons, des neunen mineralocorticoids. Experientia.
1954;10:132-133.
22. Lardon A, Schindler, Reichstein T. Eine weitere Synthese von
d, 1-Aldosteron. Helvetica Chimica Acta. 1957;40:666-674.
23. Rosenmund H, Reichstein T. Isolierung eines weiteren kristallisierten stark herzwirksamen Glycosids aus Adonis vernalis.
Pharmazeutische Acta Helvetica. 1942;17:176-185.
24. Reichstein T, Katz A. Die Constitution des Convallatoxins.
Pharmazeutische Acta Helvetica. 1943;18:521-530.
25. von Euw J, Reichstein T. Die Glykoside der Samen von
Strophantus hypoleucus Stapf. Helvetica Chimica Acta.
1950;33:666-674.
26. Reichstein T. The ferns in Flora Europaea. British Fern Gazette. 1965;9:6-14.
27. Kunz H, Reichstein T. Kleine Beiträge zur Flora Apennin.
Bauhinia. 1966;3:87-96.
28. Reichstein T. Asplenium reuteri Milde ein Bastard. Candollea.
1969;24:145-153.
29. Reichstein T. Hybrids in European Aspleniaceae (Pteridophyta): significance, recognition, genome analysis and fertility, checklist of species and hybrids. Description of some
new hybrids and cytology of several already known hybrids.
Botanica Helvetica. 1981;91:89-97.
30. Fiore C, Calo LA, Colombo L, Grimm CE, Armani D. History
of aldosterone on its 50th birthday. J Nephrol. 2006;19(Suppl
10):S124-S126.
31. Weber KT. Aldosterone and spironolactone in heart failure
[editiorial]. N Engl J Med. 1999;341:753-755.
32. Remuzzi G, Cattaneo D, Perico N. The aggravating mechanisms of aldosterone on kidney fibrosis. J Am Soc Nephrol.
2008;19:1459-1462.
Received: 6 October, 2008
Accepted: 30 June, 2009
© Società Italiana di Nefrologia
S85