Nobel Prize in Physiology or Medicine 1965
Presentation Speech by Professor Sven Gard, member of
the Nobel Committee for Physiology or Medicine of the
Royal Caroline Institute
Your Majesties, Royal Highnesses, Ladies and Gentlemen.
The 1965 Nobel Prize in Physiology or Medicine is shared by Professors
Jacob, Lwoff and Monod for «discoveries concerning the genetic regulation
of enzyme and virus synthesis».
This particular sphere of research is by no means easy. I heard one of the
prize winners, Professor Jacob, forewarn an audience of specialists more
or less as follows: «In describing genetic mechanisms, there is a choice
between being inexact and incomprehensible». In making this presentation,
I shall try to be as inexact as conscience permits.
It has become progressively more apparent that the answer to what has hitherto
been romantically termed the secret of life must be sought in the mechanism
of action and in the structure of the hereditary material, the genes. This
central field of research has naturally been approached from the periphery
and in stages. Only in recent years has it been possible to make a serious
attack on these fundamental problems.
Several previous Nobel Prize holders: Beadle, Tatum, Crick, Watson, Wilkins, Kornberg and
have worked in this sphere of research and have formulated
certain basic proposals which have enabled the French scholars to continue
their efforts. It has been established that one of the principal functions
of genes must be to determine the nature and number of enzymes within the
cell, the chemical apparatus which controls all the reactions by which the
cellular material is formed and the energy necessary for various life processes
is released. There is thus a particular gene for each specific enzyme.
In addition, some light has been thrown on the chemical structure of genes.
In principle, they have the form of a long double chain consisting of four
different components, which can be designated by the letters a, c, g, and
t, and with the property of forming pairs with each other. An «a»
in one of the chains has to be matched by a «t» in the other, a «g»
only by a «c». However, they can be linked along the length of the chain
in any order whatsoever, so that the number of possible combinations is
virtually unlimited. A chain of genes contains from several hundreds to
many thousands of units; such structures can easily carry the specific patterns
for the million or more genes which it is estimated that a cell may have.
This model of the genes represents a coded message containing two types
of information. If the double chain of a gene is split lengthwise and each
half acquires a new partner, then the final result is two double chains
identical to the original gene. The model thus contains information relative
to the actual structure of the gene, which permits multiplication, in its
turn a condition of heredity. When a cell divides, each daughter cell receives
an exact copy of the parent gene. The structure of the double chain ensures
the stability and permanence required by hereditary material.
But the model can also be read in another way. Along the length of the chain,
the letters are grouped in threes in coded words. An alphabet of four letters
allows the formation of more than 30 different words and the sequence in
the gene of such words provides the structural information for an enzyme
or some other protein. Proteins are also chain molecules built up from twenty
or so different types of building blocks. To each of these building blocks
there corresponds a chemical code word of three letters. The gene thus contains
information on the number, nature, and order of the building blocks in a
Thus it was already clear that the hereditary blueprint contained the collective
structural information for all substances necessary for the functions of
the living cell. It was not known how the genetic information was put into
effect or transformed into chemical activity. As to the function of the
genes, it was thought that they participated in a sort of procreative act
when the new cell came into being, producing new substances necessary for
the life of the cell, but subsequently lying dormant until the next cell
division. It was presumed that the structure and formation of the chemical
apparatus determined in this way defined all the regulatory mechanisms necessary
for the cell's ability to adapt to changes in the environment and to respond
in an adequate manner to stimuli of different types.
To begin with, the group of French workers were able to demonstrate how
the structural information of the genes was used chemically. During a process
resembling gene multiplication an exact copy of the genetic code is produced,
termed a messenger. The latter is then incorporated into the chemical
«workshop» of the cell and wound like magnetic tape onto a spool.
For each word arriving
on the spool, a constructional unit is attracted, which carries a complement
to this word and attaches itself there just like a piece of jigsaw puzzle.
The building blocks of a protein are selected in this way one by one, aligned,
and joined together to form a protein with the appropriate structure.
The messenger substance is, however, short-lived. The tape lasts only for
a few recordings. The enzymes are also used up in a similar way. For the
cell to maintain its activity, it is thus necessary to have an uninterrupted
production of the messenger material, that is to say continuous activity
of the corresponding gene.
However, cells can adapt themselves to different external conditions. Thus
there must exist some mechanisms controlling the activity of the genes.
The research into the nature of these mechanisms is a remarkable achievement
which has opened the way for the possible explanation of a series of hitherto
mysterious biological phenomena. The discovery of a previously unknown class,
the operator genes, which control the structural genes, marks a major breakthrough.
There are two types of operator genes. One type releases chemical signals,
which are perceived by a second, receptor, type. The latter controls in
its turn one or more structural genes. As long as the signals are being
received the receptor remains blocked and the structural genes are inactive.
Certain substances coming from outside or formed within the cell can, however,
influence the chemical signals in a specific manner, changing their character
so that they can no longer influence the receptor. The latter is unblocked
and activates the structural genes; messenger material is produced and the
synthesis of enzymes or another protein commences.
Control of gene activity is thus of a negative nature; the structural genes
are only active if the repressor signals do not arrive. One can speak here
of chemical control circuits similar in many ways to electrical circuits,
for example in a television set. In the same way, they can be interconnected
or arranged in a series to form complicated systems.
With the aid of such control circuits, the free living monocellular organism
can produce enzymes when required, or interrupt chemical reactions if they
are likely to cause damage; an excitatory stimulus can provoke movement,
flight or attack, depending on the nature of the excitation. With such mechanisms
it is possible to direct the development of cells into more complicated
structures. It is particularly interesting to note that the activity of
viruses is controlled, in principle, in the same manner.
Bacteriophages contain a genetic control circuit complete with emitter,
receptor, and structural genes. While chemical signals are being sent and
received, the virus remains inactive. When incorporated into a cell, it
behaves like a normal component of the cell, and can confer on it new properties
which may improve its chances of survival in the struggle for existence.
However, if the signals are interrupted, the virus is activated, starts
to grow rapidly and soon kills the host cell. There is considerable evidence
for the view that certain types of tumor virus are incorporated into a
normal cell in the same way, thus transforming it into a tumour cell.
We are easily inclined to hold an exaggerated opinion of ourselves in this
era of advanced technology. Thus, we are justified in having a great admiration
for the achievements in electronics, where, for example, the attempts
at miniaturization to reduce component size, to lower the weight, and reduce
the volume of apparatus have enabled a rapid development of space science.
However, we should bear in mind that, millions of years ago, nature perfected
systems far surpassing all that the inventive genius of man has been able
to conceive hitherto. A single living cell, measuring several thousandths
of a millimetre, contains hundreds of thousands of chemical control circuits,
exactly harmonized and functioning infallibly. It is hardly possible to
improve on miniaturization further; we are dealing here with a level where
the components are single molecules. The group of French workers has opened
up a field of research which in the truest sense of the word can be described
as molecular biology.
Lwoff represents microbiology, Monod biochemistry, and Jacob cellular genetics.
Their decisive discovery would not have been possible without competence
and technical knowledge in all these fields, nor without intimate cooperation
between the three researchers. But the mystery of life is not resolved simply
with knowledge and technical skill. One must also have a gift for observation,
a logical intellect, a faculty for the synthesis of ideas, a degree of imagination,
and scientific intuition, qualities with which the three workers are liberally
Research in this field has not yet yielded results that can be used in practice.
However, the discoveries have given a strong impetus to research in all
domains of biology with far-reaching effects spreading out like ripples
in the water. Now that we know the nature of such mechanisms, we have the
possibility of learning to master them, with all the consequences which
that will surely entail for practical medicine.
François Jacob, André Lwoff, Jacques Monod. Thanks to your technically
unimpeachable experiments and your ingenious and logical deductions, you
have gained a more intimate familiarity with the nature of vital functions
than anyone before you has done. Action, coordination, adaptation, variation - these
are the most striking manifestations of living matter. By placing more emphasis
on dynamic activity and mechanisms than on structure, you have laid the
foundations for the science of molecular biology in the true sense of the
term. In the name of the Caroline Institute, I ask you to accept our admiration
and our most sincere congratulations. Finally, I invite you to come down
from the platform to receive the prize from His Majesty the King.
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