The Nobel Prize in Chemistry 1993
Kary B. Mullis, Michael Smith
Presentation Speech by Professor Carl-Ivar
Brändén of the Royal
Swedish Academy of Sciences
Translation from the Swedish text
Your Majesties, Your Royal Highnesses,
Ladies and Gentlemen,
Our genetic material, which gives every living organism its unique characteristics, is built up from large and complex DNA molecules, each comprising hundreds of millions of atoms. For a long time it was believed that these molecules were outside the realm of the chemical laboratory and that their manipulation could only be achieved through the complex machinery of a living cell. This year's Nobel Laureates in Chemistry, Kary B. Mullis and Michael Smith, have drastically changed this notion by providing research tools that chemists can use outside a living cell to amplify and specifically modify any given gene.
The foundations of the conceptual framework for this development were laid down by the discovery of the double-helical nature of the DNA structure for which the Nobel Prize in Physiology or Medicine was given to Francis Crick, James Watson and Maurice Wilkins in 1962. The four building blocks of the DNA molecule, the nucleotides, are arranged in a specific order along the molecule to form a genetic code for the sequence of amino acids in the corresponding protein molecules. This genetic information is present in a complementary fashion in the two strands of the DNA molecule. Hence, one strand can serve as a template for the synthesis of the second strand. Mutations occur when the sequence of nucleotides is changed. In living cells such mutations occur randomly and evolution is therefore a trial and error process. It can easily be calculated that for a given gene only a tiny fraction of all possible combinations of these nucleotides have been made and tested during the 3.5 billion years that life has been present on Earth. Consequently, there is scope for the design of novel and interesting protein molecules provided we have the knowledge and methodology to obtain and amplify existing genes and to make appropriate changes to them.
In the 1970s, Michael Smith developed a general method for producing mutations in a gene, not in a random fashion but at specific positions determined in advance from the sequence of the nucleotides in the gene. This method of site-directed mutagenesis has created completely new opportunities to study the properties of protein molecules: how they function as catalysts or as signal transmitters through membranes, which factors determine how they fold into specific three-dimensional structures and how they interact with other molecules in the cell. Such protein engineering is also of importance in modern biotechnology and drug design. Novel antibodies have been created that can kill certain cancer cells. Plants that produce proteins enriched in essential amino acids are being field tested and in the future this method might produce engineered wheat and corn flour that has the same nutritional value as meat.
Isolation and amplification of a specific gene was one of the outstanding problems in DNA technology, including site-directed mutagenesis, until 1985 when Kary Mullis presented the Polymerase Chain Reaction, now commonly known as PCR. Using this method it is possible to amplify and isolate in a test tube a specific DNA segment within a background of a complex gene pool. In this repetitive process the number of copies of the specific DNA segment doubles during each cycle. In a few hours it is possible to achieve more than 20 cycles, which produces over a million copies.
The PCR method has already had a profound influence on basic research in biology. Cloning and sequencing of genes as well as site-directed mutagenesis have been facilitated and made more efficient. Genetic and evolutionary relationships are easily studied by the PCR method even from ancient fossils containing only fragments of DNA. Biotechnology applications of PCR are numerous. In addition to being an indispensable research tool in drug design, the PCR method is now used in diagnosis of viral and bacterial infections including HIV. The method is so sensitive that it is used in forensic medicine to analyze the DNA content of a drop of blood or a strand of hair.
Dr. Kary Mullis and Professor Michael
On behalf of the Royal Swedish Academy of Sciences I wish to convey to you our warmest congratulations for your outstanding accomplishments and ask you to receive the Nobel Prize from the hands of his Majesty the King.
From Nobel Lectures, Chemistry 1991-1995, Editor Bo G. Malmström, World Scientific Publishing Co., Singapore, 1997
Copyright © The Nobel Foundation 1993