The Nobel Prize in Chemistry 1962
Max F. Perutz, John C. Kendrew
Presentation Speech by Professor G. Hägg, member of the Nobel Committee for Chemistry of the Royal Swedish Academy of Sciences
Your Majesties, Your Royal Highnesses,
Ladies and Gentlemen.
In the year 1869 the Swedish chemist Christian Wilhelm Blomstrand
wrote, in his at that time remarkable book Die Chemie der
Jetztzeit (Chemistry of Today):
"It is the important task of the chemist to reproduce faithfully
in his own way the elaborate constructions which we call chemical
compounds, in the erection of which the atoms serve as building
stones, and to determine the number and relative positions of the
points of attack at which any atom attaches itself to any other;
in short, to determine the distribution of the atoms in
space."
In other words, Blomstrand gives here as his goal the knowledge
of how compounds are built up from atoms, i.e. knowledge of what
is nowadays often called their "structure". Moreover, structure
determination has been one of the biggest tasks of chemical
research, and has been approached using many different
techniques. For several reasons, the structure determination of
carbon compounds, the so-called organic compounds, experienced an
initial rapid development. At this stage the techniques were
generally those of pure chemistry. One drew conclusions from the
reactions of a compound, one studied its degradation products,
and tried to synthesize it by combining simpler compounds. The
structure thus arrived at, however, was in general rather
schematic in character; it showed which atoms were bonded to a
given atom, but gave no precise values for interatomic distances
or interbond angles. However, for an up-to-date treatment of the
chemical bond and in order to derive a correlation between
structure and properties, these values are needed, and they can
only be obtained using the techniques of physics.
The physical method which, more than any other, has contributed
to our present-day knowledge of these mutual dispositions of the
atoms is founded on the phenomenon which occurs when an X-ray
beam meets a crystal. This phenomenon, called diffraction,
results in the crystal sending out beams of X-rays in certain
directions. These beams are described as reflections. The
directions and intensities of such reflections depend on the type
and distribution of the atoms within the crystal, and can
therefore be used for structure determination. It is 50 years ago
this year since Max
von Laue discovered the diffraction of X-rays by crystals, a
discovery for which he was awarded the 1914 Nobel Prize for
Physics. This work opened up a whole new range of possibilities
for studying both the nature of X-rays and the structure of
compounds in the solid state. The initial application of
structure determination was developed first and foremost by the
two English scientists, Bragg father and son,
and as early as 1915 they were rewarded with the Nobel Prize for
Physics. The techniques have since been considerably refined, and
it has been possible to solve more and more complicated
structures. However, considerable difficulties were encountered
as soon as any other than very simple structures were considered.
There is no simple general way of progressing from experimental
data to the structure of the compound under investigation.
Moreover, the mathematical calculations are exceedingly
time-consuming. However, by about the middle of the 1940's a
point had been reached where it was becoming possible to carry
out X-ray determinations of the structures of organic compounds
which were so complicated that they defied all attempts using
classical chemical methods.
In 1937 Max Perutz performed some experiments in Cambridge to find out
whether it might be possible to determine the structure of
haemoglobin by X-ray diffraction, since no other method could be
imagined for this purpose. Sir Lawrence Bragg, who tirelessly
continued the work begun jointly with his father, in 1938 became
the head of the Cavendish Laboratory in Cambridge. When he saw
the results obtained by Perutz, he encouraged him to continue and
has ever since lent a very efficient support. Haemoglobin belongs
to the proteins which play such an enormous part in life
processes, and which are a basic material in living organisms.
Haemoglobin is a component of the red blood corpuscles. It
contains iron which can take up oxygen in the lungs and later
give it up to the body's other tissues. Haemoglobin is counted
among the globular proteins, whose molecules are nearly
spherical. It was chosen for the initial attempt, partly because
it could develop good crystals, and partly because the
haemoglobin molecule is quite small for a protein molecule. About
ten years later, John Kendrew joined Perutz' research group, and
the task allotted to him was to try to determine the structure of
myoglobin. Myoglobin is another globular protein, closely related
to haemoglobin, but with a molecule only a quarter as large. It
is found in the muscles, and enables oxygen to be stored there.
Particularly large amounts of myoglobin are found in the muscular
tissues of whales and seals, which need to be able to store large
quantities of oxygen when diving.
However, Perutz and Kendrew encountered considerable
difficulties. In spite of exceptionally comprehensive work, the
result was not forthcoming until 1953, when Perutz succeeded in
incorporating heavy atoms, namely those of mercury, into definite
positions in the haemoglobin molecule. By this means the
diffraction pattern is altered to some extent, and the changes
can be utilized in a more direct structure determination. The
method was already known in principle, but Perutz applied it in a
new way, and with great skill. Kendrew also succeeded, by an
alternative method, in incorporating heavy atoms, generally
mercury or gold, into the myoglobin molecule, and could
subsequently proceed in an analogous manner.
A necessary condition for this technique is that the addition of
the heavy atoms should not alter the positions of the other atoms
of the molecule within the crystal. In this connection it is
simply because of its enormous dimensions that the molecule
remains practically unaltered. Bragg has rather aptly said that
"the molecule takes no more notice of such an insignificant
attachment than a maharaja's elephant would of the gold star
painted on its forehead".
But even if the path was now open for a direct structure
determination of haemoglobin and myoglobin, there was still an
enormous amount of data to be processed. Myoglobin, the smaller
of the two molecules, contains about 2,600 atoms, and the
positions of most of these are now known. But for this purpose,
Kendrew had to examine 110 crystals and measure the intensities
of about 250,000 X-ray reflections. The calculations would not
have been practicable if he had not had access to a very large
electronic computer. The haemoglobin molecule is four times as
large, and its structure is known less thoroughly. In both cases,
however, Kendrew and Perutz are currently collecting and
processing an even greater number of reflections in order to
obtain a more detailed picture.
As a result of Kendrew's and Perutz' contributions it is thus
becoming possible to see the principles behind the construction
of globular proteins. The goal has been reached after twenty-five
years' labour, and initially with only modest results. We
therefore admire the two scientists not only for the ingenuity
and skill with which they have carried out their work, but also
for their patience and perseverance, which have overcome the
difficulties which initially seemed insuperable. We now know that
the structure of proteins can be determined, and it is certain
that a number of new determinations will soon be carried out,
perhaps chicfly following the lines which Perutz and Kendrew have
indicated. It is fairly certain that the knowledge which will
thus be gained of these substances which are so essential to
living organisms will mean a big step forward in the
understanding of life processes. It is thus abundantly clear that
this year's prize-winners in chemistry have fulfilled the
condition which Alfred Nobel laid down in his will, they have
conferred the greatest benefit on mankind.
Doctor Kendrew and Doctor Perutz. One of
you recently said that today's students of the living organism do
indeed stand on the threshold of a new world. You have both
contributed very efficiently to the opening of the door to this
new world and you have been among the first to obtain a glimpse
of it. Through your combined efforts there is now in view, as it
has been stated by yourself, a firm basis for an understanding of
the enormous complexities of structure, of biogenesis and of the
functions of living organisms both in health and disease.
It is with great satisfaction, therefore, that the Royal Swedish
Academy of Sciences has decided to award you this year's Nobel
Prize for Chemistry for your brilliant achievement.
On behalf of the Academy I wish to extend to you our heartiest
congratulations, and now ask you to receive from the hands of His
Majesty the King the Nobel Prize for Chemistry for the year
1962.
From Nobel Lectures, Chemistry 1942-1962, Elsevier Publishing Company, Amsterdam, 1964
Copyright © The Nobel Foundation 1962
We are currently working on the web site. Please report errors or problems.
