Early in the summer of 1961, a young Japanese organic chemist named Osamu Shimomura wedged himself into a station wagon packed with lab equipment and three other passengers and drove across the United States looking for the secret of what makes certain jellyfish glow in the dark. His discovery--a luminescent protein that glows green under ultraviolet light, known as green fluorescent protein (GFP)--and its development into one of the most powerful imaging tools for molecular biology earned Shimomura and two Americans this year's Nobel Prize in chemistry.
Shimomura, who recently retired from the Marine Biological Laboratory in Woods Hole, Massachusetts, set out for the West Coast to collect samples of the jellyfish Aequorea victoria and ultimately discovered GFP. In 1994, Columbia University neurobiologist Martin Chalfie and colleagues reported in Science that they successfully cloned the gene for GFP into Escherichia coli bacteria and the Caenorhabditis elegans worm and could use its luminescence to track the expression of neighboring genes (Science, 11 February 1994, p. 802). That set off an avalanche of interest in using GFP as a marker to investigate everything from how cells develop to what makes cancer cells metastasize. Researchers led by University of California, San Diego, biochemist Roger Tsien then picked up the baton and created an extended family of proteins that fluoresce a palette of colors across the visible spectrum. These enable biologists today to simultaneously track the expression of multiple genes and other molecules inside cells.
"The fluorescent proteins have revolutionized medical research," says oncologist and imaging expert John Frangioni of Harvard Medical School in Boston. Last year, more than 12,000 papers reported using GFP and other fluorescent proteins, according to Marc Zimmer, a chemist at Connecticut College in New London and author of Glowing Genes, a book about the discovery of fluorescent proteins. Today, GFP and other fluorescent proteins "are probably as important as the development of the microscope," he says. That underscores the value of basic research: If Shimomura's pursuit of jellyfish fluorescence were funded today, says Zimmer, it would be more likely to earn scorn than anything else. "It's a great candidate for the IgNobels" (ScienceNOW, 3 October).
Zimmer and others agree that Shimomura, Chalfie, and Tsien are all deserving of the prize. Frangioni calls them "a wonderful choice." For his part, Tsien says he's been aware of the rumors in recent years of a possible Nobel for his GFP research. But the actual phone call itself that aroused him from his sleep still came as a shock. "I feel a little bit like a deer caught in the headlights," Tsien says.