Lowly jellyfish spurs lofty recognition

OCT 08, 2008

Jason Socrates Bardi

Inside Science News Service: 2008 Nobel Prize in Chemistry goes to Three U.S. Researchers for the Discovery and Development of Green Fluorescent Protein, a Tool for Illuminating the Unseen.

“Nature’s first green is gold,” the poet Robert Frost once wrote, and this morning his words held true for three researchers at American institutions who just won the 2008 Nobel Prize in Chemistry for their discovery and development of green fluorescent proteinâmdash;a molecule found inside jellyfish that has revolutionized biology and medicine.The prize, awarded annually by the Swedish Academy and carrying a cash amount of $1.4 million, will be split evenly among the three winners: Osamu Shimomura of the Marine Biological Laboratory in Woods Hole, MA, and Boston University Medical School; Martin Chalfie of Columbia University in New York; and Roger Y. Tsien of the University of California, San Diego.

Though the prize is awarded in chemistry, the discovery is one that cuts across many fields of science. At the heart of the discovery is the green fluorescent protein (GFP), a molecule that naturally “fluoresces” or glows by absorbing light of one color and reemitting it as another color. As a research tool, the protein has revolutionized biology and medicine, says Jeremy M. Berg, the director of the director of the National Institute of General Medical Sciences, a component of the National Institutes of Health.

“GFP is part of the fabric of biomedical research,” Berg said in an interview. “It has become an essential tool for looking at gene expression in all types of organisms.

“How and where genes are expressed in the body is one of the most fundamental aspects of all human health and disease. What GFP allows scientists to do is to tag proteins—the products of genes—with the molecular equivalent of a beacon. That allows them to look through microscopes at living cells and tissues and observe which genes are acting where in the body. This sort of information sheds light on basic biology and addresses some of today’s most important medical questions.

“Green fluorescent proteins allow scientists quite literally to see the growth of cancer and study Alzheimer’s disease and other conditions that affect millions of people,” American Chemical Society President Bruce E. Bursten said in a statement today.

Connecticut College Professor Marc Zimmer, author of the book “Glowing Genes: A Revolution in Biotechnology” and an expert on the history of GFP, compared the discovery of GFP to that of the microscope, which revolutionized science in the 17th century.

“It is just as significant as the microscope,” said Zimmer, “because it allows us to see things we have never seen before.”

Shimomura first isolated the glowing protein in the jellyfish Aequorea Victorea, which drifts along currents off the west coast of North America. According to Zimmer, Shimomura caught a million of these jellyfish over the course of 20 years and from them isolated the mysterious glowing substance in 1962. Shimomura described how it absorbs light of one color and reemits a different colored light in a paper he published at the time: “a protein giving solutions that look slightly greenish in sunlight though only yellowish under tungsten lights, and exhibiting a very bright, greenish fluorescence in the ultraviolet . . .”

What Shimomura originally dubbed “green protein” was later renamed green fluorescent protein, or GFP for short, after the physical basis of the protein’s glow was better understood. GFP, like all proteins, is a string of amino acid molecules that spontaneously folds into a particular shape. The unique shape of the folded protein allows it to absorb light of one color and emits it as a separate color (the characteristic green).

Many biological molecules are capable of producing such a glow. One of the most familiar is the protein luciferase, the “phosphorescent” molecule responsible for the glow of the firefly at twilight in the summer. What is unique about GFP, however, is that unlike luciferase, which relies on a complicated chemical conversion to make light, GFP simply converts one color of light into another. What happens in the jellyfish is that a completely different protein handles the chemical conversion and feeds a blue light to GFP, which absorbs the blue and emits the green.

Because GFP is relatively small and has such an elegantly simple mechanism, researchers in the modern laboratory can attach it like a tag to almost any gene product. Then simply by shining light on a sample, they can observe where the tagged gene products are distributed, what they are interacting with, and ask some of the most fundamental questions about how biology works. For example, this basic procedure can show how genes act during embryonic development of simple organisms, it can show how the immune system interacts with pathogens, and it can even illuminate the intricate details of neurons inside a mouse’s brain.

It was co-laureate Chalfie of Columbia University who first demonstrated the value of GFP as a genetic tag that can literally illuminate various biological phenomena. In one of his first experiments, he used GFP to color and tag six individual cells in the roundworm Caenorhabditis elegans. Since this early work, GFP tagging has been adopted and applied to essentially every type of organism studied in the laboratory, from bacterial colonies to human cells.Nowadays, the technique is even more powerful thanks to the work of co-laureate Tsien of UCSD. He enhanced the technique by creating a color palette that extends beyond green. He has developed tags of numerous colors, which allows scientists to follow several different biological processes at the same time and to see how multiple types of cells and proteins interact.

The one irony of all this is that to date nobody has been able to figure out what purpose GFP serves in the jellyfish. “Is it used for hunting, for attracting partners, or something else?” asks NIGMS’s Berg. “I don’t think anyone really knows.”

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