Nobel Discovery Gave Green Light to Biomedicine Studies

Jellyfish plays lead role in the prize for work on fluorescent protein.

Roger Tsien developed ways to alter GFP to emit different colors.

In today's laboratories, data output from all manner of advanced-imaging technologies, rich computer simulations and molecular reactions can be stunningly beautiful. The dashes of color, lines, and configurations that take shape in research measurements are surely pretty, and they give scientists unheard-of opportunities to witness the physical world in action—literally before our eyes.

Yesterday, two Americans and a Japanese living in the United States were awarded the Nobel Prize in chemistry for pioneering a dazzling visualization technique that has become one of the most-important tools in modern bioscience, the Royal Swedish Academy of Sciences said. Based on the protein that makes jellyfish glow in the dark ocean, the method allows scientists to watch processes that were once invisible, such as the development of nerve pathways in the brain or how cancer cells spread.

The prize rewards both the initial discovery of green fluorescent protein, or GFP, which lies at the heart of the technique, and later developments that led to GFP's wide use as tool to illuminate cellular movement and gene activity and chemical reactions within cells. With the genomes of so many organisms now known, scientists are at work figuring out the "proteome"—the properties and interactions of the tens of thousands of different proteins those genes encode.

GFP was first isolated by laureate Osamu Shimomura, now an emeritus professor at the Marine Biological Laboratory in Woods Hole, Mass., from baseball-size crystal jellyfish that inhabit waters off the coast of Washington State.

In 1961, barely 15 years after his studies were disrupted by the atomic bombing of Japan, Shimomura took an arduous cross-country drive from Princeton—his home campus at the time—to Washington's Friday Harbor Laboratory, to find the elusive protein in jellyfish that were plentiful there. He and fellow Princeton scientist, Frank Johnson, set up shop in a small two-room building.

"There were three other scientists in the room," Shimomura wrote in a 1995 account of the discovery, "and one of them was Dr. Dixy Lee Ray, future governor of Washington State, who was always accompanied by a dog, her wellknown trademark. The laboratory area was a sanctuary prohibited to common dogs, but she declared that the animal was her assistant, not a dog."

Eventually, Shimomura and Johnson coaxed the glowing substance from "squeezates" of the creature's outer bell and isolated the light-reactive protein, GFP. Chemical analysis revealed the relatively simple mechanism by which GFP emits fluorescent green light, which also made it remarkably easy to adapt to more complex uses.  

Without Shimomura's pioneering research, the academy said, "it is likely the GFP revolution would have been delayed by decades or even remained one of the hidden secrets of the Pacific Ocean."

But the revolution did march on. Two other laureates, Martin Chalfie and Roger Tsien, engineered ways to use GFP as a tracer molecule and made variations capable of producing a palette of eye-popping colors, which allows scientists to follow several different biochemical processes at once.

A geneticist at Columbia University, Chalfie studies a tiny but very important roundworm to understand nervous-system development. The worm's genome has been sequenced, and the lineage of each of its 959 cells from fertilization to the adult animal is known. After successfully getting GFP to light up in the bacterium E. coli, Chalfie tried it in the multi-celled worm. He attached the GFP gene to a genetic switch responsible for generating a nerve-cell protein and then watched the protein's green glow—and its nerve cells—move throughout the worm's body as it developed from a fertilized egg.   

Chalfie's experiments solidified GFP's durability and usefulness as a marker in a variety of organisms.

Meanwhile, laureate Roger Tsien, a professor at the University of California, San Diego, and a Howard Hughes Medical Institute investigator, has spent his career developing fluorescent protein probes, many of which are based on GFP.