The Nobel Prize in Physiology or Medicine 1959
Severo Ochoa, Arthur Kornberg
Presentation Speech by Professor H. Theorell, member of the Staff of Professors of the Royal Caroline Institute
Your Majesties, Your Royal Highnesses,
Ladies and Gentlemen.
To maa man vaere hvis livet skal lykkes, «There must
be two if life shall succeed», is the theme of a sentimental
old Danish song. The author had in mind man and woman, but she
probably did not know how right she was from a more elementary
biological viewpoint. Two principles are necessary so that
«life» shall «succeed». One consists of
proteins, the other of nucleic acids. The analogy is more than
just a play upon words. Just as man and woman are responsible for
the regeneration of mankind, likewise is the interplay between
proteins and nucleic acids the only, and universally repeated
basic mechanism of life. In the long series of substances which
build up viruses, bacteria, plants, and animals, everything else
might vary, but the proteins and nucleic acids are always present
as the life-supporting elements. These both show certain
principal characteristics. Their molecules are very large, and
are built up from thousands of smaller units linked together in
chains - just like a string of pearls - which have a tendency to
form helices. Single helices join together in complicated threads
which can contain proteins or nucleic acids or both. In the mixed
«super molecules», the reactions of life proceed in the
subtle pattern of the intimately associated strands.
The proteins contain amino acids as their elementary part. In the
whole of Nature on this earth, there are found only some twenty
amino acids in proteins. The elementary parts of the nucleic
acids, the nucleotides, consist of nitrogenous bases, sugar, and
phosphoric acid. There are found in Nature practically no more
than eight of these most important nucleotides, all of which
contain phosphoric acid, but in which the nitrogenous base may be
one of five different kinds. The sugar can be of two different
kinds, one of which, «ribose», contains one more oxygen
atom than the other, «deoxyribose». This seemingly
insignificant difference in a single atom produces a remarkably
great effect. Nucleic acids are divided into two different series
because of this characteristic. These series have widely
different functions, so widely different in fact, that this is
the reason why we have two Prize Winners on the stage
today.
«Deoxyribonucleic acids», which Arthur Kornberg has now
synthesized, are mainly present as the hereditary substance in
chromosomes. The «ribonucleic acids», which Severo
Ochoa has synthesized, have other functions, such as to assist in
the synthesis of proteins. The Swedish scientist Torbjörn
Caspersson has played an important role in demonstrating this
last fact. From his and other research-workers' discoveries, it
has been possible to conclude that nucleic acids assist in the
synthesis of protein. The exact chemical mechanism, however, is
as yet unknown. Inasmuch as nucleic acids and proteins are the
two main principles of life, it seemed highly probable that,
vice versa, the proteins should take part in the
rebuilding of nucleic acids. This seems so much the more probable
when we realize that proteins, in the form of enzymes, take part
in practically every chemical reaction in the biological world.
It is to the everlasting credit of Ochoa and Kornberg to have
clarified this fundamental mechanism by preparing proteins that
build up nucleic acids in test tubes.
For proteins it has been proved, and for the nucleic acids it is
highly probable, that the order of the different building blocks
in the chains is by no means left to chance, but on the contrary
is planned in detail for each kind of molecule and for each kind
of living organism.
It is this regulated order between the building blocks that
always makes human children grow up to be human beings, and the
serpent's offspring grow up to be serpents. It is disturbances in
this regulated order which change the hereditary factors and
allows the variations of species over thousands of years. The
almost infinite possibilities to combine the building blocks in
different ways makes it possible to vary the form in which life
appears on our earth. Let me give a comparable example. By
different combinations of the 28 letters in our alphabet, we can
write everything that can be expressed in our own language, as
well as in all other languages. The building blocks of the
proteins, the amino acids, are approximately equal in number to
the letters of the alphabet. The protein molecules can be
compared with words with 100, 1,000, or even 10,000 letters. It
is clear that Nature here has been generous with the possibility
to make different combinations amounting to astronomical figures.
But here, another factor might be brought up. The differences
between the amino acids are necessary not only to produce the
possibilities for variation, but also to enable the proteins, by
their enzymatic activity, to regulate the different aspects of
metabolism. Even the two types of nucleic acids with 4 different
nucleotides in each, when made up from 100 to 10,000 nucleotide
units in each molecule, give a fantastic number of possible
combinations. Thus it would seem as if it were too heroic an
enterprise to try to find out the procedure whereby Nature forms
such complicated substances as nucleic acids with such an
unerring accuracy in placing each building block.
A few years ago, Ochoa and Kornberg, each in his own laboratory,
started to investigate the problem. The development turned for
Ochoa's part in a direction that made him work with systems that
produced ribonucleic acids, while for Kornberg it led him to
investigate the formation of deoxyribonucleic acids. They have
both, in a series of outstanding investigations, without direct
cooperation, but nevertheless, as personal friends probably
profiting from each other's results, reached the goal at the same
time. As everyone else, they were able to make use of results
obtained by preceding research workers, among whom I can only
mention a few. It might be of interest to mention that uric acid,
the first representative of the purines (a class of nitrogenous
bases that form part of the nucleic acids) was discovered in
Sweden in 1776 simultaneously by both Carl Wilhelm Scheele and
Torbern Bergman. It is a curious parallel to the shared Nobel
Award of today, and a reminder of Sweden's great era in the
science of chemistry. The German scientist Albrecht Kossel received the Nobel Prize
in 1910 for his elucidation of the chemistry of the nitrogenous
bases of the nucleic acids, whereas the English scientist
Alexander Todd
clarified in detail the chemical properties of the nucleic acids,
and received the Nobel Prize for Chemistry in 1957. But what
really enabled Ochoa and Kornberg to succeed was their own
excellent previous work in related fields. Both have worked with
bacteria from which they have made preparations of a high degree
of purity, Ochoa from an acetic acid bacterium, and Kornberg from
the coli bacterium. Ochoa's enzyme produces ribonucleic
acids from ribonucleotides having twice the ratio of phosphoric
acid residues as that contained in ribonucleic acid. The
ribonucleic acid is formed by splitting out half of the
phosphoric acid residues, and linking the nucleotides together to
form large molecules, which, as far as we can prove today, do not
differ in any way from natural nucleic acids. Kornberg's enzyme
produces deoxyribonucleic acids in a similar, but not identical
fashion. Both have arrived at the same, principally important
result that in order to make the reaction start, it is necessary
to add in the beginning a small amount of nucleic acid to act as
a template. Otherwise the enzymes do not «know» which
kind of nucleic acid they are to produce. As soon as they get a
template to act as a guide, they start, just like a skilled
type-setter, to copy the «manuscript» they have
received. Here one recognizes life's own principle that like
creates like. Even though several research workers had earlier
suspected that such a mechanism was involved, the actual
experimental proof is of greatest importance. Furthermore,
Ochoa's enzyme has given us the possibility of enzymatically
synthesizing simplified nucleic acids of great interest.
To give an idea of where the discoveries that are being honored
today may lead to in the near future, I want to mention one
example. Other scientists, especially S. S. Cohen in the U.S.A.,
have shown that the nucleic acid of a certain bacteriophage,
T2, which is a kind of bacterial virus, contains a
somewhat chemically different nitrogenous base. If bacteria are
infected with T2 phage, this different nucleic acid is
soon produced in the bacteria. Kornberg succeeded in explaining
the mechanism in detail. T2 phage behaves like the
worst kind of usurper. Within four minutes it produces a number
of enzymes which destroy a nucleotide necessary for the
bacterium's normal production of nucleic acids, and rebuilds it
to the different nucleotide of the T2 phage, and
thereby destroys the bacteria.
We are sure to witness in the near future several important
discoveries in biochemistry, virus research, genetics, and cancer
research as a consequence of the work of Ochoa and Kornberg. They
have helped us to advance quite some distance on the road to
understanding the mechanism of life.
Professor Severo Ochoa, Professor Arthur
Kornberg, dear friends and colleagues. Some 130 years ago,
Friedrich Wöhler, in the laboratory of Berzelius,
synthesized urea from inorganic matter. This event occurred in
the heart of this city of Stockholm, less than half a mile from
where we are now standing. He thus overbridged the first gap
between living and dead material. You have now made the second
fundamental discovery on this pathway, the synthesis in test
tubes of one of the two basic principles of life.
On behalf of the Caroline Institute, I extend to you our warm
congratulations, and ask you to receive this year's Nobel Prize
for Physiology or Medicine 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 1959
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