Former University researcher wins chemistry Nobel

Shimomura will share the 10 million krona ($1.4 million) prize with Columbia University biology professor Martin Chalfie and University of California-San Diego pharmacology professor Roger Tsien.

While Shimomura is credited with first discovering GFP, Chalfie and Tsien helped develop a method for using GFP and genes as biological markers or tagging mechanisms.

In a press conference Wednesday, Gary Borisy, the director of the Marine Biological Laboratory at Woods Hole, with which Shimomura is currently affiliated, called GFP “God’s gift to molecular [and] cell biologists” because it “allowed people to visualize” an enormous variety of biological processes.

Shimomura learned that he had been selected for the Nobel Prize at 5 a.m. Wednesday when he received a phone call at his home in Falmouth, Mass.

“My wife answered first, and she told me it was from Stockholm. I think she knew already,” he said in at the press conference. “I had not expected [to win] ... because mine was just the discovery of the protein. I didn’t think this had [a direct connection] to chemistry. I think this was very unexpected ... but I am very happy.”

A remarkable journey

Born in Kyoto in 1928, Shimomura, the son of a Japanese army colonel, lived just 10 kilometers from Nagasaki when it was devastated by the atomic bomb in 1944. He was partially blinded by the explosion.

“I thought I was looking at ghosts, in broad daylight,” Shimomura told Vincent Pieribone and David Gruber, who wrote a book about the history of research on biofluorescence in 2005.

“My heart was frozen, my brain became unfeeling and the sound of cicadas stopped. That quiet scene was imprinted in my memory much stronger than any other bloody or gruesome scene I had ever seen,” Shimomura said.

“There was no choice in our future,” he told Pieribone and Gruber. “We just had to live.”

Even before the atom bomb, however, Shimomura’s high school education was disrupted by the war, and as a result, he took his education into his own hands.

He said Wednesday morning that “most of my knowledge came by self study” but did not mention how the war affected him as a teenager.

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Shimomura eventually received his Ph.D. in organic chemistry from Nagoya University in Japan. In early fall 1960, he arrived at Princeton Junction, where, according to Pieribone and Gruber, he was met by biology professor Frank Johnson ’30, who a year earlier had invited the promising young Japanese scientist to come to Princeton and offered to pay for his trip. Shimomura, however, applied for and received a Fulbright scholarship instead.

Upon arriving on campus, Pieribone and Gruber wrote, Johnson promptly took Shimomura to a laboratory room in Guyot Hall.

In a 1995 essay, Shimomura explained how he and Johnson embarked on the unlikely project of studying jellyfish.

“He asked me if I would be interested in studying the bioluminescence of this jellyfish,” Shimomura wrote. “I was quite impressed by Dr. Johnson’s description of the brilliant luminescence of live jellyfish and the great abundance of specimens around Friday Harbor, Washington. So my response was a definite ‘yes.’ ”

In 1961, Shimomura’s work with Johnson led them to Friday Harbor, where they tried throughout the summer to isolate or extract the luminescent substance in the jellyfish.

The unusual task attracted a lot of attention, Shimomura said in his 1995 account, explaining that he regularly had to stop his work to explain to passersby that the creatures were being used for research.

“I cannot forget a funny exchange that took place one early morning,” he wrote. “An old lady poked her head out from the window of a small boat, looked at the jellyfish on my net, and asked me, ‘How do you cook them?’ I answered, ‘We don’t cook those jellyfish.’ She gazed at me distastefully, ‘Do you eat them raw?’ and her head disappeared. ‘No! We don’t eat them!’ But my reply was too late.”

Their efforts met with little success until midway through the summer, when Shimomura made the surprising discovery that seawater triggered the luminescence.

By the time they returned to Princeton, they had extracted the luminescent substance from about 10,000 jellyfish and packed it in dry ice.

Delayed gratification

In 1962, Shimomura managed to isolate GFP and another luminescent protein, aequorin, from the jellyfish. But the significance of his discovery did not come to light until many years later.

“In the 1960s, when the Japanese scientist Osamu Shimomura began to study the bioluminescent jellyfish Aequorea Victoria, he had no idea what a scientific revolution it would lead to,” according to a statement from the Nobel Foundation.

Indeed, Shimomura said at the press conference that he did not know the importance of his discovery until 1994.

Shimomura’s discovery, combined with Chalfie and Tsien’s innovations 30 years later, has critically transformed contemporary biological and medical research. Because it is luminescent and immediately visible to the naked eye, GFP has played an important role in the field of biological tagging and helped scientists tremendously in their studies of gene expression.

According to the Nobel statement, GFP has been used to “illuminate growing cancer tumours; show the development of Alzheimer’s disease in the brain or the growth of pathogenic bacteria.”

President Tilghman, who joined the Princeton faculty as a biology professor four years after Shimomura left Princeton in 1982, said that she used the GFP protein in her own work.

“I found it to be a very valuable tool to study the dynamic patterns of gene expression during development,” she said in an e-mail.

“It is often the case that science is moved ahead by the development of technology at least as much if not more than by the introduction of new ideas,” she added. “GFP is an example of a discovery of a protein that was turned into a tremendously useful tool for biologists.”

In the press conference, Shimomura encouraged young scientists to relentlessly pursue any subjects that interest them, regardless of how unlikely or unsuccessful the work may seem.

“Don’t stop, don’t give up. If you find difficulty, just overcome that,” he said.