Presentation Speech
by Professor Arne Fredga of the Royal Academy of Sciences
Translation
from the Swedish text
Your Majesties, Your Royal
Highnesses, Ladies and Gentlemen,
The laureates in chemistry of this
year have both studied reaction mechanisms, especially from a stereochemical,
i.e. a geometrical point of view. In a chemical experiment some compounds are
mixed, then something happens, and finally one can isolate one or more other compounds.
What has really happened, and why, and how? The situation is as if someone had
abbreviated a classical tragedy, say Hamlet, by showing only the opening scenes
of the play and the final scene of the last act. The principal characters are
introduced, then the scene closes and when the curtain rises again you see a number
of dead bodies on the stage and a few survivors. Of course the spectators would
like to know what has happened in the meantime.
What
I have said is valid not least for enzymatic reactions. Many such reactions are
perpetually going on in all living organisms; one could say that they really concern
all of us although we don't observe them. When a chemist tries to find out what
really happens, he often comes across the problem: right or left? It is the same
in common life. If you leave Stockholm by Norrtull, you soon come to a place where
the main road branches: the left branch leads to Oslo, the right one to Sundsvall
or, if you like, to Haparanda.
Professor Cornforth has
among other things studied the biological synthesis of the hydrocarbon squalene
from six molecules of mevalonic acid. This hydrocarbon is necessary for the formation
of steroids, which are of vital importance in many respects. The synthesis of
squalene takes place in 14 steps and at each the enzyme must find the proper way.
That means that there are just 214 = 16384 different routes and only
one of them leads to squalene. If the enzyme should make a mistake in the first
step (which it does not), the final result could be rubber or various other things
but definitely not squalene. The problem at each step concerns which of two hydrogen
atoms is to be eliminated, the right one or the left one. Professor Cornforth
has shown which choice the enzyme makes at each of the 14 steps. For this purpose
he has, with brilliant mastership, utilized the properties of the hydrogen isotopes:
the ordinary hydrogen, the heavy hydrogen and the radioactive hydrogen. The lastmentioned
isotope can only be used in tracer quantities, which means that only about one
part per million of the participating molecules are radioactive. In a similar
way, Professor Cornforth has studied several other biologically important reactions.
All problems connected with the reaction mechanisms are not solved at that point,
but the results constitute a very important step on the way.
Professor
Prelog has worked in many fields of stereochemistry, and often the problems have
been connected with the geometrical shapes of the molecules and their influence
on the course of the reactions.
An impressive series
of investigations deal with the "medium rings", i.e. molecules containing rings
of 8 to 11 carbon atoms. Such rings are not rigid but rather limp. Parts of the
ring which may seem rather distant may come into close contact with each other
leading to unexpected reactions. Professor Prelog has been able to elucidate such
reactions by utilizing the carbon isotopes.
Many important
investigations refer to reactions between chiral molecules. The term chiral is
derived from a word in ancient Greek, meaning hand. The molecules are unsymmetrical
and may exist in two forms differing in the same way as a right hand and a left
hand. The molecules are so small that you can't see them, but one can gain much
knowledge by studying the reactions between chiral molecules of different kind.
Professor
Prelog has also made important contributions to enzyme chemistry. He has studied
enzymatic reactions on small molecules and in particular oxidation or reduction
processes. The experiments may be more or less successful depending on how the
enzyme and the other molecule fit together geometrically. By systematic experiments
with various small molecules of well-defined shapes, it was possible to construct
a "map" of the active part of the enzyme molecule. The results have recently been
confirmed in a special case by Swedish scientists using x-ray methods.
Professor
Prelog has also with ingenuity and penetration discussed and analysed the fundamental
concepts of stereochemistry, not least the conditions for chirality in large and
complicated molecules.
Professor Cornforth. Enzymatic
reactions have always had a certain air of magic, perhaps witchcraft. Of course
this is due to our imperfect knowledge of what really happens. This air of magic
is, however, gradually dispersing, and your contributions, utilizing the isotopes
of hydrogen, imply most striking advances. The handling of compounds with chiral
methyl groups is an achievement of the highest intellectual standard.
Let
me also express our admiration for the skill and perseverance with which you have
pursued your work in spite of a serious physical handicap. Perhaps it had not
been possible without the never-failing help and support of Mrs. Cornforth. I
think she should not be forgotten on this day. In recognition of your services
to chemistry and to natural science as a whole, the Royal Academy of Sciences
has decided to confer upon you the Nobel Prize. To me has been granted the privilege
to convey to you the most heartly congratulations of the Academy.
Professor
Prelog. Ich habe hier versucht, einen Kurzbericht über Ihre wichtigsten Leistungen
in der Stereochemie zu erstatten. Das war gewiss etwas schwierig. Ihre schönen
Experimentalarbeiten erstrecken sich über weite Felder der heutigen organischen
Chemie. Öfters haben Sie die Fortführung Ihrer Arbeiten anderen Forschern
überlassen, und viele Chemiker hohen Ranges sind zurzeit auf den Gebieten
tätig, die Sie einst eröffnet haben. Sie haben auch die fundamentalen
Grundlagen der Stereochemie, besonders den Chiralitätsbegriff, in tiefsinnigen
Auseinandersetzungen diskutiert und klargelegt.
In Anerkennung
Ihrer Verdienste um die Entwicklung der Chemie hat die Konigliche Akademie der
Wissenschaften entschlossen, Ihnen den Nobelpreis zu verleihen. Mir ist die Aufgabe
zugefallen, Ihnen die wärmsten Glückwünsche der Akademie zu überbringen.
Professor
Cornforth. In the name of the Academy I invite you to receive your prize from
the hands of His Majesty the King.
Professor Prelog,
Im Namen der Akademie bitte ich Sie aus den Händen Seiner Majestät des
Königs den Nobelpreis in Empfang zu nehmen.
From Nobel Lectures, Chemistry 1971-1980, Editor-in-Charge Tore Frängsmyr,
Editor Sture Forsén, World Scientific Publishing Co., Singapore, 1993
Press Release: The 1975 Nobel Prize in Chemistry
17
October 1975
The Royal Swedish Academy of Sciences has decided
to award the 1975 Nobel Prize in Chemistry with one half to
Professor
John Warcup Cornforth, England for his work on the stereochemistry
of enzyme-catalyzed reactions
and with the other half to
Professor Vladimir Prelog, Switzerland for his research
into the stereochemistry of organic molecules and reactions
Cornforth has been awarded the Prize for his work on the stereochemistry of
enzyme-catalyzed reactions. This subject is difficult to explain to the layman
as it is a question of geometry in three dimensions; it is concerned with the
delicate mechanism of important reactions in biological systems, where a group
of atoms takes the place of a certain hydrogen atom among two or three, which
may appear to be equivalent. The problem is to decide which of the hydrogen atoms
is replaced and if nearby groups retain their positions or if they are rearranged
in some way. The enzyme leads the process in a quite uniform way. Without this
guidance, chaos would break out in the biological system.
Cornforth
"marks" the hydrogen atoms by making use of hydrogen's three isotopes; ordinary
hydrogen (mass 1), heavy hydrogen or deuterium (mass 2) and radioactive hydrogen
or tritium (mass 3). He then makes use of their differing reaction speeds (the
lightest reacts the quickest). Only trace quantities of tritium can be used; no
more than a millionth or so of the molecules involved in the reaction are marked.
The planning of this research is an outstanding intellectual achievement. Among
the biologically significant reactions the stereochemistry of which has been clarified
is the synthesis of steroids from mevalonic acid via squalene and the condensations
of acetate with glyoxylic acid to malic acid and with oxalylacetic acid to citric
acid. Since Cornforth has shown the way similar research has been initiated in
other quarters.
The Prize has been awarded to Professor Prelog
for his research into the stereochemistry of organic molecules and reactions,
i.e. the connection between the course of chemical reactions and the geometric
form of the participating molecules. His research spans a wide field.
One area of study has been "medium-sized rings" - ring-shaped molecules with 8-12
carbon atoms. A ring of this kind is fairly mobile one might almost say "flaccid"';
apparently remote parts of the molecule can come into close contact with each
other thus causing unexpected reactions. Medium-sized rings are not unusual in
nature.
Another important area of his research is that concerned
with chiral molecules, formerly called assymetric molecules. The word "chiral"
comes from the Greek meaning "hand" and signifies that the molecules can have
two forms differing from one another as the right hand does from the left. Prelog
has done very significant research on reactions between chiral molecules. This
research is of fundamental importance to an understanding of biological processes.
Prelog has also led a very penetrating discussion of the conditions governing
chirality in complex molecules.
Prelog has experimented with enzymes
acting on simple molecules, where the result depends on how the compound and the
enzyme "suit one another". Systematic experiments with simple compounds of well-defined
structures give valuable information about the structure of enzymes and the way
they act.
It should perhaps be mentioned that Professor
Prelog has also done extensive research on special groups of natural products,
e.g. alkaloids and antibiotics from microorganisms, where his profound knowledge
of stereochemistry has been of great advantage.
Vladimir
Prelog – Autobiography
I was born
on July 23rd, 1906 in Sarajevo in the province of Bosnia, which then belonged
to the Austrian-Hungarian Monarchy and later, in 1918, became part of Yugoslavia.
In the western world my birthplace has a somewhat sinister reputation that was
characterized by an older tax-inspector in the Midwest of America as "the place
where all that mess started". Actually, as an 8 years old boy I stood near to
the spot where Archiduke Franz Ferdinand and his wife were assassinated. At the
beginning of the first World War, in 1915, we moved to Zagreb, the capital of
Croatia, where I attended the gymnasium. The period 1924 to 1929 was spent studying
Chemistry at the Czech Institute of Technology in Prague, Czechoslovakia. The
supervisor of my thesis was Professor Emil Votocek, one of the prominent founders
of chemical research in Czechoslovakia. My mentor, however, was Rudolf Lukes,
then lecturer and later successor of Votocek to the chair of organic chemistry.
To Lukes I owe the greatest part of my early scientific education, and he remained
my close friend until his premature death in 1960. In addition to these two "real"
teachers I admired Robert Robinson, Christopher Ingold and Leopold Ruzicka, all
of whom I considered as my "imaginary" teachers. In later years I was fortunate
to become well acquainted with all three of these great chemists.
The close of my studies with a degree of a Dr. Ing. in 1929 coincided with the
great economic crisis, and I was not able to find an academic position. I was
therefore very grateful for a position in the newly created laboratory of G.J.
Dríza in Prague where rare chemicals were produced on small scale. I had
there also a modest opportunity to do some research, but I badly wanted to work
in an academic environment. This is why I was so eager to accept the position
of a lecturer at the University of Zagreb in 1935. I did not know that I had to
fulfil there all the duties of a full professor and to live on a salary of an
underpaid assistant, but it would probably not have affected my decision if I
had known. With the help of a couple of enthusiastic young co-workers and of a
developing small pharmaceutical factory, I had just managed to solve at least
the most urgent problems for myself and my laboratory when the second World War
broke out. After the German occupation of Zagreb in 1941 it became clear that
I was likely to get into serious trouble if I remained there. At this critical
point I received an invitation of Richard Kuhn to give some lectures in Germany,
and shortly afterwards Leopold Ruzicka, whom I had asked for help, invited me
to visit him on the way. With these two invitations, it was possible for me to
escape with my wife to Switzerland. Through Ruzicka I soon obtained generous support
of CIBA Ltd. and started work in the Organic Chemistry Laboratory at the Federal
Institute of Technology (ETH) in Zurich. The cooperation with Ruzicka lasted many
years and enabled me to make my slow progress up the academic hierarchical ladder.
Starting as assistant, I became "Privat Dozent", "Titularprofessor" associate
(ausserordentlicher) professor and in 1952 full professor ad personam. Finally,
in 1957, I succeeded Ruzicka as head of the Laboratory, a height that I never
dreamt of when I was a student in Prague. In becoming director of the Laboratory
I reached, according to Peter's principle, the level of my incompetence and I
tried hard for several years to step down. Surrounded and supported by a group
of very able young colleagues, I finally succeeded in introducing a rotating chairmanship
from which I was exempted. So far this has worked very satisfactorily and it may
have helped some of my colleagues to resist tempting offers from other Universities.
My main interests were natural compounds, from adamantane and aialoids
to rifamycins and boromycin. During the work on natural compounds stereochemical
problems emerged from all sides. As E.L. Eliel pointed out, stereochemistry is
not so much a branch of chemistry but rather a way of looking at chemistry. It
was, and still is, great fun trying to find new points of view for it.
I travel a lot. Recently I counted that I have given lectures in more than 150
places, often several times. This in spite of the fact that I do not speak any
language properly. I suspect that many people come to my lectures because they
enjoy my strange accent and skill in managing without actually cheating.
I married my wife Kamila in Prague in 1933. A son Jan was born to us in
Zürich in 1949.
For many years, when still a Yugoslav citizen,
I was already a Swiss patriot and in 1959 I obtained Swiss citizenship. However,
I consider myself a world citizen and I am very grateful to my adopted country
that it allows me to be one.
The way from Sarajevo to Stockholm is
a long one and I am fully aware that I have been very lucky to arrive there. The
journey could not have been made without the generous help of friends, colleagues,
co-workers and also of innumerable earlier chemists "on whose shoulders we stand".
From Les Prix Nobel en 1975,
Editor Wilhelm Odelberg, [Nobel Foundation], Stockholm, 1976
This autobiography/biography was written
at the time of the award and later published in the book series Les Prix Nobel/Nobel
Lectures. The information is sometimes updated with an addendum submitted
by the Laureate. To cite this document, always state the source as shown above.
For more updated biographical information, see: Prelog,
Vladimir, My 132 Semesters of Studies of Chemistry. Oxford University Press,
Oxford, 1998.
I was born
on July 23rd, 1906 in Sarajevo in the province of Bosnia, which then belonged
to the Austrian-Hungarian Monarchy and later, in 1918, became part of Yugoslavia.
In the western world my birthplace has a somewhat sinister reputation that was
characterized by an older tax-inspector in the Midwest of America as "the place
where all that mess started". Actually, as an 8 years old boy I stood near to
the spot where Archiduke Franz Ferdinand and his wife were assassinated. At the
beginning of the first World War, in 1915, we moved to Zagreb, the capital of
Croatia, where I attended the gymnasium. The period 1924 to 1929 was spent studying
Chemistry at the Czech Institute of Technology in Prague, Czechoslovakia. The
supervisor of my thesis was Professor Emil Votocek, one of the prominent founders
of chemical research in Czechoslovakia. My mentor, however, was Rudolf Lukes,
then lecturer and later successor of Votocek to the chair of organic chemistry.
To Lukes I owe the greatest part of my early scientific education, and he remained
my close friend until his premature death in 1960. In addition to these two "real"
teachers I admired Robert Robinson, Christopher Ingold and Leopold Ruzicka, all
of whom I considered as my "imaginary" teachers. In later years I was fortunate
to become well acquainted with all three of these great chemists.