Nobel Prize in chemistry commends finding and use of green fluorescent protein

Making cells glow with a protein borrowed from jellyfish is one of the brightest ideas in chemistry. At least that is what the RoyalSwedishAcademy of Sciences implied when it announced October 8 that the 2008 Nobel Prize in chemistry would be awarded to three scientists who were instrumental in discovering green fluorescent protein, commonly called GFP, and developing the protein as a powerful tool for basic biological research.

Osamu Shimomura, Martin Chalfie and Roger Tsien will equally share the $1.4 million prize.

GFP can absorb light at one energy and emit light at another. The result is that the protein glows, and glows with a specific color, when exposed to a specific wavelength of light. This function differs from that of bioluminescent proteins, which can generate their own light.

“There’s no doubt that GFP has changed the way we do biology,” says Jeff Lichtman, a neuroscientist at HarvardUniversity. “There’s a wide range of things that can be done with GFP that are just unthinkable without it.” For instance, scientists can watch the movement of proteins within a cell or track the migration of cells throughout the body.

Shimomura, of both the Marine Biological Laboratory in Woods Hole, Mass., and of BostonUniversity, first discovered the barrel-shaped protein in jellyfish called Aequorea victoria in 1962. He collected more than a million jellyfish in Friday Harbor, Wash., and extracted light-producing chemicals from the animals. While purifying a protein called aequorin, which produces blue light in response to rising calcium levels in a cell, Shimomura found another protein that absorbs the blue light from aequorin and then gives off green light.

The discovery of a fluorescent protein astounded many scientists, says Marc Zimmer, a computational chemist at ConnecticutCollege in New London. Inside GFP sits a chromophore, a structure of rings that absorbs light and then emits light of lower energy. Until GFP was discovered, all of the fluorescent molecules known in nature were either not proteins or were pairs of proteins, in which each member performed chemical surgery on the other and gave off light as a byproduct of the reaction, he says.

So it came as a shock to find that GFP could twist and turn on itself, attacking and rearranging its amino acids to form a five-sided ring and giving off water and light.

“You have here a protein that has figured out how to do surgery on its own gut,” says Tsien. “If you had asked us before GFP came along whether a protein could do this, we would have said, ‘absolutely not.’ It would be almost as if a protein could lift its wings and start flying through the air. It would be almost as ludicrous.”

Since the discovery of the jellyfish protein, at least 125 different species have been found to contain individual proteins that are fluorescent, all with a shape and a method for emitting light that is similar to GFP, Zimmer says.

Shimomura said during an Oct. 8 teleconference that he didn’t expect to win the chemistry prize for his basic research on jellyfish. He didn’t realize the practical uses of the green fluorescent protein until Chalfie’s lab succeeded in producing the protein in another organism, and retaining the protein’s ability to fluoresce, he said.

But the Japanese-born scientist “was the obvious choice” to win a Nobel for his discovery of the molecule, says Zimmer. At least four other scientists had a hand in developing the protein into a powerful research tool, but no more than three people can share a Nobel Prize. “It must have been very difficult to make the choice,” Zimmer says.

Chalfie, of ColumbiaUniversity, first heard about the protein in a seminar. He immediately realized that if he could put a fluorescent protein into the cells of the transparent roundworm Caenorhabditis elegans he could see which cells produced the light. He developed the gene that encodes the fluorescent protein as a biological tag and showed its usefulness by coloring six cells in the roundworm. Even before he published the results of his experiments in 1994, Chalfie distributed the technology for introducing GFP into living cells to researchers around the world.

Now the use of fluorescent proteins is ubiquitous in biology. “I don’t know anyone who isn’t using it,” Lichtman says. “The Green Revolution, as I call it, has become such a dominant technology, I worried that it wouldn’t get the prize because it would be taken for granted.”

Tsien, of the University of California, San Diego in La Jolla and of the Howard Hughes Medical Institute, tweaked the structure of the jellyfish protein and a red fluorescent protein found in corals to make them glow in a rainbow of colors from the deepest purples to true red. That ability enables scientists to track a number of different proteins or cells at once, allowing for a deeper understanding of biological interactions.

In 1968, at age 16, Tsien won the top prize in the Westinghouse Science Talent Search competition (now the Intel Science Talent Search). His project explored the orientation of an ion in transition-metal complexes. The competition is owned and operated by Society for Science & the Public (then Science Service), which publishes Science News.

Lichtman uses a Crayola box of fluorescent proteins —most developed by Tsien — to color neurons in mouse brains. He and his colleagues can watch the neurons grow and develop and form and break connections with each other in living animals. Such experiments only became possible with the fluorescent proteins, he says.

“I’m just very pleased,” Lichtman says. “If I have to have any qualm at all it is about the missing person,” Douglas Prasher. Prasher was the first to isolate the gene that encodes GFP, but he had difficulty making it fluoresce when produced in another organism. His discovery of the gene made Chalfie’s and Tsien’s work possible. “I’m a bit sad that he didn’t get to share in this prize, but all three deserve it,” Lichtman says.

The Nobel Prize committee announced the winners at 5:45 a.m. EST Wednesday, October 8. Laureates are informed of their selection before the announcement of the prize, but Chalfie says he slept through the congratulatory phone call from the Swedish academy because he had muted his phone a few days earlier. He woke up about 25 minutes later to a faintly ringing phone and recalled that the chemistry prize was being awarded. “I decided to find out who the schnuck was who won it this year,” he said during the October 8 teleconference. “I opened up my laptop and discovered that I was the schnuck. The other two are very good scientists,” he quipped.

SN staff writer Rachel Ehrenberg contributed to this article.

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Past Science News stories chronicling the work of this year’s Nobel Prize winners:
	“Chemical Revelations: Tattletale molecules make cells grow.” Science News, 1993 Download PDF
	“Jellies and their Twinkling Protein.” Science News, 1997 Download PDF
	“Protein’s structure lights the way.” Science News, 2000.
	Photocap. Science News, 2000.