Presentation Speech by Professor Bo G. Malmström of the Royal Academy of Sciences

Translation from the Swedish text

Your Majesties, Your Royal Highnesses, Ladies and Gentlemen,

Life is order, death is disorder. A fundamental law of Nature states that spontaneous chemical changes in the universe tend toward chaos. But life has, during milliards (American English billions) of years of evolution, seemingly contradicted this law. With the aid of energy derived from the sun it has built up the most complicated systems to be found in the universe – living organisms. Living matter is characterized by a high degree of chemical organisation on all levels, from the organs of large organisms to the smallest constituents of the cell. The beauty we experience when we enjoy the exquisite form of a flower or a bird is a reflection of a microscopic beauty in the architecture of molecules.

The chemical order of life is not maintained by some mysterious vital force. The secret of life is instead to be found in chemical properties which are the consequence of the very structural organisation of atoms and molecules. Modern structural chemistry has here provided tools for opening the door to one of the greatest mysteries of science.

The structure of chemical substances, i.e. the exact position in space of all the atoms in a molecule, can generally be determined if the substance can be obtained in the form of crystals. When X-rays are scattered from the periodic arrangement of the atoms in a crystal, a specific pattern is formed, which can be recorded photographically and translated to the original structure with the aid of a complicated mathematical analysis. The principle of this method, called X-ray diffraction, has been known since the beginning of this century, and its discovery was awarded with a Nobel Prize in physics in 1915. Almost half a century elapsed, however, before the technique had developed to a point allowing the determination of the structure of the giant molecules which are the building blocks of life. In 1962 the Nobel Prizes in chemistry as well as in medicine were awarded to scientists who had studied the molecular structure of the key substances of life, proteins and nucleic acids.

A nucleic acid, DNA, is carrier of the traits of heredity in the cell. Consequently it possesses all information necessary to direct the entire chemical machinery of the cell, and it does so by determining which proteins the cell shall manufacture. Proteins in turn determine the chemical pattern of the cell by their ability to speed up certain chemical reactions. Life can thus be regarded as the result of an interplay between nucleic acids and proteins.

Giant molecules have a tendency to aggregate, and biological function is often associated with complicated molecular aggregates. In the chromosomes of the cell nucleus, for example, the hereditary material is present in the form of chromatin, a giant aggregate between DNA and thousands of protein molecules. In viruses, which represent the border between living and dead matter, there are simpler aggregates between nucleic acids and proteins. A virus can be said to be genetic material without a cell of its own, and the structure of viruses can provide clues to the more complicated organisation of the hereditary material in higher organisms.

Large molecular aggregates can seldom be obtained in a form which allows structural determination by X-ray diffraction. The investigator who has been awarded with this year’s Nobel Prize in chemistry, Aaron Klug, has developed a method to study the structure of molecular aggregates from biological systems. His technique is based on an ingenious combination of electron microscopy with principles taken from diffraction methods. Electron microscopy has long been used to depict the structural components of the cell, but its power of resolution is after, limited by a lack of contrast in the picture. Klug has shown that even picture; seemingly lacking in contrast may contain a large amount of structural information, which can be made available by a mathematical manipulation of the picture.

With this technique, in combination with other methods of structural chemistry, Klug has inter alia investigated viruses and chromatin of the cell nucleus. His virus studies have illuminated an important biochemical principle, according to which the complicated molecular aggregates in the cell are formed spontaneously from their components. The chromatin investigations have provided clues to the structural control of the reading of the genetic message in DNA. In a long-term perspective they will undoubtedly be of crucial importance for our understanding of the nature of cancer, in which the control of the growth and division of cells by the genetic material no longer functions.

Dr. Klug,

I have tried to say – in Swedish – that with your ingenious development of crystallographic electron microscopy you have given science an important tool for determining the chemical structure of complicated components in the most refined chemical systems found in the universe – living organisms. You have applied your methods to investigations of viruses and of chromatin, the complex molecular aggregate between DNA and proteins in cell nuclei, and your structural results have clarified important biochemical principles. It is for these fundamental contributions that the Royal Academy of Sciences has decided to award this year’s Nobel Prize in Chemistry to you.

On behalf of the Academy I wish to convey to you our warmest congratulations, and I now ask you to receive your prize from the hands of His Majesty the King.