A Light in the Dark

Photograph of Rodger Tsien

Roger Tsien

Paul Fetters

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Aequoria victoria, the luminescent jellyfish that lives in the frigid waters off the Northwest Pacific coast, sparked an exciting notion that began 40 years ago with a simple question: What if one could find the molecule responsible for the creature’s glow? Next came a bigger question: What if one could pluck that protein from this marvelous animal and use it as a beacon to illuminate the inner workings of the cell? What if?

Today, the Howard Hughes Medical Institute celebrates three visionary scientists—Osamu Shimomura of the Marine Biological Laboratory, Martin Chalfie of Columbia University, and Roger Tsien, an HHMI investigator at the University of California, San Diego—who had the tenacity to follow that notion to its realization. Their perseverance in asking “what if” and extending the limits of what is visible have helped others make remarkable discoveries about how the biological world works. The three were honored in December 2008 with the Nobel Prize in Chemistry for the discovery and development of green fluorescent protein, or GFP, a research tool that has revolutionized the biological sciences.

GFP once existed only in nature’s laboratory. It remained hidden inside the gossamer “umbrella” that girds the jellyfish A. victoria. The path to GFP began in 1962 with Shimomura’s identification of the GFP protein, but it wasn’t until 1984 that Douglas Prasher, a scientist at the Woods Hole Oceanographic Institution, cloned the GFP gene. Two years later, Prasher and Chalfie demonstrated that GFP could be used as a marker for gene expression.

The Story of GFP

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The Nobel Foundation recognized Tsien for his work developing GFP markers to watch proteins in action. By manipulating genes from the glowing jellyfish and from corals, Tsien created a set of genes that produce a dazzling array of hues, including cherry, strawberry, tangerine, tomato, orange, banana, and honeydew. These genes allow scientists to tag any of the tens of thousands of proteins at work in the body to observe what they do and, by marking multiple proteins, how they interact.

Today, fluorescent proteins are so ubiquitous that scientists can order them through various catalogs. And GFP’s utility goes far beyond human biology as well; it’s been used to create bacteria that glow in the presence of arsenic, a significant problem in well water in Southeast Asia, and to identify explosives such as TNT.

As Tsien has noted with a certain degree of admiration, A. victoria is a born chemist. Its dazzling iridescent light shows are the product of feats no human chemist can match. “A single jellyfish gene directs 238 ordered condensations, plus one cyclization, plus one oxidation,” Tsien stated in his Nobel speech in Stockholm on December 10, 2008. “It’s all done in a few minutes … with only one slightly toxic byproduct and an essentially 100 percent yield of an extremely useful product that literally glows green.”

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Photo credit: Slide 1: Steven Haddock/Trevor Rivers, MBARI Slide 2: Copyright © Nobel Web AB 2008 Photo: Annalisa Andersson Slide 3: Copyright © Nobel Web AB 2008 Photo: Mia Åkermark Slide 4: Courtesy of Tsien Lab Slide 5: Jessica Vasale/Mello Lab Slide 6: Utpal Pal, Ruth R. Montgomery, Erol Fikrig Slide 7: From Science Vol 312, Issue 5771, 14 April 2006. Reprinted with permission from AAAS Slide 8: Courtesy of Roger Tsien Lab Slide 9: Livet, Sanes, Lichtman Center for Brain Science, Harvard University, Cambridge MA Slide 10: Courtesy of Roger Tsien Lab