Presentation Speech by Professor Måns Ehrenberg, Member of the Royal Swedish Academy of Sciences; Member of the Nobel Committee for Chemistry, 10 December 2008

Professor Måns Ehrenberg delivering the Presentation Speech for the 2008 Nobel Prize in Chemistry at the Stockholm Concert Hall. Copyright © The Nobel Foundation 2008 Photo: Hans Mehlin

Your Majesties, Your Royal Highnesses, Ladies and Gentlemen,

Since its very beginning, molecular biology research has focused on the genetic information embedded in the DNA sequences of chromosomes. Although the success of DNA research is impressive, DNA sequences provide but one dimension of the multidimensional and dynamic processes that define the behaviour of organisms from the movement of their molecules to their ecological patterns. The discovery and development of the green fluorescent protein (GFP) have radically changed the scientific agenda. Improved variants of GFP and GFP-like proteins in synergy with high-resolution microscopes, computational techniques and powerful theoretical approaches are currently fuelling a scientific revolution focused on quantitative analyses of complex biological systems. The gradual appearance of a world of hitherto unseen structures and dynamic principles is now impacting virtually all aspects of biological, medical and pharmaceutical research.

The story of GFP has three acts: the discovery of GFP, the expression of fluorescing GFP in key model organisms and the development of GFP-like proteins into a universal set of genetic tags.

The first act began in Japan fifty years ago, when Osamu Shimomura studied the self-luminous small crustacean ostracod Cypridina. His successful work brought him to the US, where he collaborated with Professor Frank Johnson in the study of the green self-luminescence of the jellyfish Aequorea victoria, peacefully swimming in the waters of the Pacific Ocean outside Friday Harbor, Washington State. In 1961 Shimomura made the surprising discovery that the protein aequorin, responsible for the self-luminescence of A. victoria, emits blue and not green light. Fortunately, he also discovered the green fluorescent protein now known as GFP, and was able to eventually explain that the green light from the jellyfish was due to electronic excitation of GFP by radiation-less transfer of blue self-luminescence from aequorin, followed by emission of green fluorescence from GFP. Thanks to Professor Shimomura’s discovery, GFP with its remarkable optical properties was pulled out from its hiding place in the Pacific and made available for scientific scrutiny.

In the beginning of the second act, hardly anyone believed that expression of GFP in organisms other than A. victoria would lead to a fluorescent protein. It was generally assumed that formation of its chromophore would require enzymes specific to A. victoria, but there was one GFP believer named Martin Chalfie who had a different view. His research focused on the nervous system of the small roundworm Caenorhabditis elegans. He was filled with enthusiasm for the experiments that would become possible if only one could express fluorescent GFP in C. elegans. Using a GFP clone provided by researcher Douglas Prasher, he demonstrated in 1993 and 1994 that brightly fluorescent GFP was expressed in both E. coli and C. elegans. Professor Chalfie’s results not only showed the power of experiments over scientific prejudice but also made it clear to many that GFP was destined to become a universal genetic marker.

The third act of the GFP story began in 1994, when Roger Tsien explained how the chromophore of GFP can form spontaneously in the presence of oxygen and engineered a GFP variant with blue fluorescence, demonstrating that point mutations in the primary structure of GFP can modulate its fluorescence emission spectrum. Since then, Tsien has provided many engineered variants of GFP. They fluoresce throughout the whole visible spectrum, have enhanced photostability and brightness as well as greatly reduced time for their chromophore to mature into its fluorescent state after protein folding. GFP has revolutionised the biological sciences, thanks to the creative engineering of continuously improved forms of GFP and GFP-like proteins carried out by Professor Tsien.

Professors Shimomura, Chalfie and Tsien:
You are rewarded for the discovery and characterisation of the green fluorescent protein, for first expressing GFP in fluorescent form in important model organisms and for the development of GFP and its homologues to a universal set of genetic tags for protein localisation, protein movement and protein interactions in the cells of all types of organisms.  On behalf of the Royal Swedish Academy of Sciences, I wish to convey to you our warmest congratulations, and I now ask you to step forward to receive the Nobel Prize in Chemistry from the hands of His Majesty the King.