Presentation Speech by Professor Claes Gustafsson, Member of the Royal Swedish Academy of Sciences; Member of the Nobel Committee for Chemistry, 10 December 2015.
Your Majesties, Your Royal Highnesses, Esteemed Nobel Laureates, Ladies and Gentlemen,
A fertilised egg cell contains all the information needed to create a human being, and this information is stored in our genetic material, our DNA. The discovery of DNA is ascribed to Friedrich Miescher, who isolated a new substance from white blood cells in 1869. Miescher performed his work in the kitchen of a castle in Tübingen, using dirty bandages that he collected daily from a local hospital as his raw material. The pus that formed around infected wounds contained large quantities of white blood cells, and from these Miescher isolated nuclein, which we call DNA today. Sixty years later, Phoebus Levene demonstrated that DNA consisted of nucleotides with four different bases, and in the 1930s two Swedish scientists, Torbjörn Caspersson and Einar Hammarsten, succeeded in demonstrating that these nucleotides were linked into very long DNA chains. But at the time, it seemed unreasonable that such a simple, repeated molecule as DNA was capable of coding all the information needed to create something as complex as a human being. The first experimental evidence that DNA was actually the bearer of genetic information was not published until 1944, when Oswald T. Avery showed that DNA transferred between different strains of pneumococcus can change the traits of the recipient bacterium.
The next important step came when biochemist Erwin Chargaff, using paper chromatography, was able to show that the relative numbers of the four bases in DNA co-varied. Chargaff’s conclusion, along with the Xray crystallographic images of DNA produced by Rosalind E. Franklin and Maurice H. Wilkins, later provided the foundation for the ingenious molecular model building that enabled James D. Watson and Francis H. Crick to suggest the structure of DNA, which was published in Nature in 1953. Like magic, this now explained how the seemingly simple DNA molecule can store genetic information that can be passed on to new generations of cells. The DNA molecule consists of two complementary strands that can separate and then be used as the template for synthesis of new DNA. This is how DNA is copied each time a cell divides, and in the course of millions of years the genetic material is transferred continuously to new generations.
The discovery that genetic information is stored in DNA, and an understanding among the greatest scientific achievements of the 20th century. But how is it possible for a chemical molecule like DNA to be so stable over time? Random errors occur in all chemical processes. In addition, our genes are subjected every day to radiation and reactive molecules that we know will damage DNA.
What keeps our DNA so astonishingly intact is a host of molecular repair mechanisms. A swarm of proteins monitor our genes. Damage to our DNA is continuously being repaired, and mistakes that occur during DNA replication are corrected. This year’s Nobel Prize in Chemistry is being awarded to three scientists who have mapped these fundamental processes at a molecular level of detail. Tomas Lindahl’s work succeeded in showing that spontaneous chemical processes cause thousands of potentially devastating damages to the genome of a cell every day. He concluded that there must be molecular systems that repair all these spontaneous damages, thereby opening the way to an entirely new field of research. Through his work, he was able to identify and characterise the repair mechanism that we know today as base excision repair. Paul Modrich studied how a cell can correct the base mismatches that sometimes occur during DNA copying. Through careful studies, he was able how this information is passed down to new generations, are for so-called mismatch repair. Today we know that this system corrects 99.9% of all the errors that occur during replication of human genetic material. DNA can also be damaged by external factors, among them ultraviolet light and smoking. Damage that occurs in this way can be removed with the help of nucleotide excision repair. Our third Laureate, Aziz Sancar, has identified the components that build up this system and has explained in molecular detail how they work together to correct DNA damage.
Tomas Lindahl, Paul Modrich, and Aziz Sancar:
Your studies of DNA repair have revealed in finest molecular detail an amazing set of repair mechanisms that ensures the integrity of our genetic material. That is a truly great achievement. On behalf of the Royal Swedish Academy of Sciences I wish to convey to you our warmest congratulations. May I now ask you to step forward and receive your Nobel Prizes from the hands of His Majesty the King.