A UC San Diego pharmacologist and two other U.S.-based scientists won the 2008 Nobel Prize in Chemistry on Wednesday for their development of a green fluorescent protein from jellyfish that has provided researchers their first new window into the workings of the cell since the development of the microscope.
Roger Y. Tsien, 56, of UC San Diego; Martin Chalfie, 61, of Columbia University; and Osamu Shimomura, 80, a Japanese-born researcher who works at the Marine Biological Laboratory in Woods Hole, Mass., will share the $1.4-million prize for developing the protein that the Nobel committee called "a guiding star for biochemists, biologists, medical scientists and other researchers."
The protein can be attached to any of the 10,000 individual molecules within a living cell, allowing researchers for the first time to trace their paths as they wind through the complex pathways of life.
It is "an essential piece of the scientific toolbox," said Jeremy M. Berg, director of the National Institute of General Medical Sciences, which has funded work by all three scientists. "It is impossible to overstate the impact of these investigators' work on scientific progress."
In a hastily arranged news conference Wednesday morning, Chalfie said he had slept through early morning phone calls from Sweden and did not know about the prize until he woke up and checked his laptop.
"It's not something out of the blue, but you never know when it's going to come or if it's going to come, so it's always a big surprise when it actually happens," he said.
Shimomura told the Japanese broadcaster NHK that he was surprised to receive the chemistry Nobel "because I was rumored as a potential candidate for the Nobel Prize in Physiology or Medicine."
In a telephone news conference, Tsien said he felt "a bit like a deer caught in the headlights. . . . Fundamentally, I'm no smarter today than I was yesterday."
The story of the fluorescent protein starts with Shimomura. In 1953, he was hired as an assistant in the Nagoya University laboratory of biologist Yoshimasa Hirata, who assigned him to discover what made the remains of a crushed mollusk glow when it was moistened with sea water.
Hirata had considered the project so difficult that he would not assign it to a graduate student for fear that its failure would prevent him from receiving his degree. But within three years, Shimomura had isolated the protein.
When Shimomura was later recruited to join Frank Johnson at Princeton University, Hirata arranged for Nagoya to award him his doctorate, even though Shimomura was not enrolled as a student.
In the summer of 1961, Shimomura and Johnson began collecting bioluminescent jellyfish in Friday Harbor in the San Juan Islands of Washington state, returning to Princeton with extracts from 10,000 of them.
From this material, they isolated a blue luminescent protein called aequorin and a green fluorescent protein, commonly called GFP. In subsequent studies, Shimomura found that GFP absorbed ultraviolet light and emitted a green glow. What was revolutionary about the protein was that -- unlike, for example, the light-emitting chemicals in the firefly -- it did not require the addition of any chemical additives.
In 1988, Chalfie heard about GFP and thought it would be useful for tracing the fate of proteins in the roundworm, Caenorhabditis elegans, which is widely used in biological studies because it is transparent, allowing researchers to study its organs under a microscope.
When Douglas Prasher of the Woods Hole Oceanographic Institution isolated the gene for GFP, Chalfie assigned graduate student Ghia Euskirchen to insert the gene into the bacterium Escherichia coli. Within a month, she had produced a bacterium that glowed green.
Next, Chalfie attached the gene to receptors in C. elegans that are involved in the sensation of touch. The cover of the journal Science in February 1994 showed a picture of the organism with the touch neurons glowing bright green.
Tsien, who at age 16 won the prestigious Westinghouse Science Talent Search for a project that examined how metals bind to organic compounds, also received a copy of the gene from Prasher. He intended to use it as a marker as well, he said, but Chalfie beat him into print.
Tsien's work with his colleague Susan Taylor required markers with two different colors, so he studied the color-producing part of GFP and devised ways to alter its gene to produce variants that glowed cyan, blue and yellow. Eventually, he and other researchers produced a family of proteins that glowed in a whole spectrum of colors, allowing researchers to follow the path of several different proteins simultaneously.
Tsien is careful to note that he did not discover GFP or use it to make any groundbreaking biological discoveries. "I'm the guy who makes the tools," he said.
One memorable experiment with the new technology tagged mouse brain proteins yellow, cyan and red, producing a mouse whose brain glowed in the colors of a rainbow -- a "brainbow," as it was tagged.
Researchers have subsequently adapted the technology so that microorganisms will glow in the presence of heavy metals, explosives such as TNT and other chemicals, allowing the microorganisms to be used as sensors to find the materials in the environment.
GFP is now used in some toys and even in art. In 2000, Chicago artist Eduardo Kac commissioned the creation of a green-glowing bunny named Alba.
All the researchers thanked their colleagues, but Tsien went one step further and thanked the jellyfish as well. "None of this would have happened without the jellyfish," he said.
But there still remains one major mystery, according to the Nobel committee: No one yet knows the purpose of the jellyfish's glow.