Published online 8 October 2008 | Nature | doi:10.1038/news.2008.1159


Great glowing jellyfish! It's the Nobel Prize in Chemistry

Green fluorescent protein bags the biggest gong in science.

jellyfishAequorea victoria, source of the green fluorescent protein.G. OCHOCKI/SCIENCE PHOTO LIBRARY

The molecule responsible for a jellyfish's glow has won its discoverer and developers this year's Nobel Prize in Chemistry.

The green fluorescent protein (GFP) has revolutionized medical and biological science by providing a way to track the activity of individual proteins within a living cell, and thereby monitor how genes are expressed.

The prize is shared equally between three scientists: Osamu Shimomura, now an emeritus professor at the Marine Biological Laboratory in Woods Hole, Massachusetts, Martin Chalfie of Columbia University in New York, and Roger Tsien at the University of California, San Diego.

Shimomura started the whole thing off in the early 1960s when he investigated what made the jellyfish Aequorea victoria glow. He collected thousands of the creatures and managed to isolate a fluorescent protein he called "green protein"1.

Gene genius

Fast-forward to 1992, when Martin Chalfie learned that Douglas Prasher at the Woods Hole Oceanographic Institute, Massachusetts, had managed to isolate the gene that expresses GFP. Chalfie built on this when a graduate student called Ghia Euskirchen, now a research scientist at Yale University, joined Chalfie's lab to do a short project. Luckily, Euskirchen had experience in fluorescence microscopy and had just the expertise needed to see what Chalfie was looking for: whether the gene for GFP could be expressed in the bacterium Escherichia coli.

It could2. But the glow of the E. coli cells was almost missed: "I couldn't see it in Marty's lab," Euskirchen tells Nature. But she took the cells to her old lab in the chemical engineering department at Columbia, where a better microscope picked out the telltale fluorescence.

Chalfie's team quickly found that if an existing gene is replaced with the gene encoding GFP, the cellular mechanism to turn on the original gene actually ends up making GFP, which can be seen under blue or ultraviolet light.

An alternative approach is to insert the GFP gene next to a gene that expresses a protein of interest. When the protein is generated, it is automatically attached to GFP, allowing scientists to track its progress through a cell or even through an entire organism.

Chalfie went on to show that GFP could be used as a tag for almost any protein in any organism. It has even been used to watch the HIV virus invading a human cell in real time.

Galloping jellyfish

brainbow cellsIn 'Brainbow' transgenic mice, nerve cells randomly express fluorescent proteins of different colours.J. LIVET et al.

The technique has galloped ahead thanks to the third laureate, Roger Tsien, who looked at the molecular detail of GFP3 and tweaked the protein to produce different coloured analogues. His work has, among other things, allowed scientists to see when proteins interact — by labelling each one with a different colour.

At the time of the announcement from Stockholm, the prize committee hadn't been able to reach Chalfie on the phone to tell him the news. "We have sent an e-mail, so he will know when he turns on his computer," the Nobel representative said.

Tsien, on hearing the news, said that Prasher was an obvious omission from the list of laureates. But the prize can only go to a maximum of three people. "I'm sure the committee had a difficult decision," Tsien says.

As in many previous years, the chemistry prize has a biological theme. But this shouldn't upset chemists, says Marc Zimmer, a computational chemist at Connecticut College who works on trying to make GFP better and brighter. "Tsien is a hard-core chemist," he says, "and Shimomura is certainly a chemist — he was interested in the structure of the protein. [GFP] is applied in biology, but all the work came from chemistry."

brainbow cellsThe combination of cyan, yellow and red fluorescent proteins highlights motor neuron axons in a 'Brainbow' transgenic mouse.J. LIVET et al.

The use of GFP is ubiquitous in many fields of biochemistry and biology. "A lot of people don't even mention GFP [in their papers] any more," says Jeremy Berg, director of the National Institute of General Medical Sciences, one of the US National Institutes of Health in Bethesda, Maryland. A simple search for papers containing the words 'green fluorescent protein' brings up more than 30,000 papers, says Berg.

It is now even possible to buy glowing pets thanks to GFP. Zebra fish, genetically engineered to contain GFP, are widely available. "I have some in the office," says Zimmer, who uses the fish when visiting schools to explain his work. 

  • References

    1. Shimomura, O., Johnson, F. H. and Saiga, Y. J. Cell. Comp. Physiol. 59, 223–239 (1962).
    2. Chalfie, M. et al. Science 263, 802–805 (1994).
    3. Ormö, M. et al. Science 273, 1392–1395 (1996).
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