Woods Hole cell biologist wins Nobel Prize

October 8, 2008 12:13 PM Email| Comments (2)| Text size – +

Aequorea, the fluorescent jellyfish Osamu Shimonura studied. (Osamu Shimomura, Woods Hole website)

By Andrew Ryan, Globe Staff

A cell biologist from the Marine Biological Laboratory in Woods Hole won the Nobel Prize in chemistry today for the discovery of a green glowing protein in jellyfish that has helped scientists illuminate growing cancer tumors and track the development of Alzheimer’s disease in the brain.

REUTERS/Adam Hunger

Osamu Shimomura, who also works at Boston University Medical School, shared the prize with two other scientists. The 80-year-old grew up in Nagasaki, Japan, and had his education disrupted as a teenager by the devastation of the atomic bomb.

In the 1960s, Shimomura began studying bioluminescent jellyfish and discovered that a florescent green protein glowed blue under ultraviolet light. The breakthrough has helped researchers follow the processes inside individual cells, allowing scientist to understand how cancer and other diseases spread.

"This morning I got the call at 5 a.m.," said Shimomura, who lives in Falmouth, at a press conference in Woods Hole. "I was in very deep sleep. My wife answered and told me it was from Stockholm. She knew already."

Shimomura urged young people to chase their interests, even if they face a difficult path. In particular, he told new scientists not to shy away from challenging subjects.

"Don't stop. Don't give up," Shimomura said. "If you encounter difficulty, overcome that until you finish the project."

"I'm a graduate of a very, very small college," continued Shimomura, who attended the Nagasaki College of Pharmacy. "Even local college graduates can get a Nobel Prize."

Shimomura told reporters that he was not expecting to receive the award because "my accomplishment was just the discovery of a protein and it doesn't have any connection to chemistry."

"I think this is very unexpected," Shimomura said. "I'm surprised, but I'm very happy."

Shimomura shared today's prize with Martin Chalfie from Columbia University and Roger Y. Tsien from the University of California, San Diego. Thirty years after Shimomura's discovery, Chalfie used the jellyfish’s green fluorescent protein to study cells. Tsien deepened that understanding.

The florescent protein "has functioned in the past decade as a guiding star for biochemists, biologists, medical scientists and other researchers," the Royal Swedish Academy of Sciences said in its description of the award.

Here is how the academy described Shimomura's work:

The story of its discovery starts in Japan in the years after the Second World War. Osamu Shimomura’s education was disrupted by the war and the devastation caused by the atom bomb. Despite this, in 1955 he was employed as an assistant by Professor Yashimasa Hirata at Nagoya University.

Professor Hirata put him to work on a seemingly impossible project – to discover what made the remains of a crushed mollusc, Cypridina, glow when it was moistened with water. It may seem strange that Hirata gave such an inexperienced assistant such a difficult task. A leading American research group had tried for a long time to isolate this material, so Hirata decided that he did not want to give the job to a student who needed to succeed in order to get his or her doctorate.

In 1956, against all odds, Shimomura had the material in his hand. It was a protein that glowed 37,000 times more brightly than the crushed mollusc. After publishing his results, Shimomura was recruited to the prestigious University of Princeton in New Jersey, USA, by Frank Johnson.

As a farewell present, Professor Hirata saw to it that Shimomura was awarded a Ph.D. from Nagoya University – an unusual act, as he was not actually enrolled as a doctoral student. After a long journey across the Pacific Ocean and the American continent, Shimomura set about studying another naturally luminescent material. This time it was from the jellyfish Aequorea victoria, whose outer edge glows green when the jellyfish is agitated.

During the whole of the summer of 1961, Shimomura and Johnson gathered jellyfish in Friday Harbor on the west coast of North America. They cut off the edges of the jellyfish and pressed them through a filter to get what they called a "squeezate." One day when Shimomura poured some of the squeezeate into the sink, it flashed brightly. He realized that there was seawater in the sink and that it was calcium ions in the seawater that had caused the chemical reaction.

Strangely enough, the flash of light was not green like the edges of the jellyfish. It was blue. Johnson and Shimomura gathered raw material throughout that summer and took back squeezate from about 10,000 jellyfish to Princeton. It took them a few months to purify just a few milligrams of the blue luminescent material from the liquid. This protein they named aequorin.

In the 1962 scientific publication, in which Shimomura and Johnson described the process by which aequorin was obtained, they also mentioned that they had isolated a protein that was slightly greenish in sunlight, yellowish in the light from a light bulb and fluorescent green in UV light. This was the first time that anyone had described GFP. Shimomura and Johnson called it the green protein but later it was named the green fluorescent protein.

In the 1970s, Shimomura looked more closely at GFP’s fluorescence. He showed that GFP contains a special chromophore, a chemical group that absorbs and emits light. When UV light or blue light hits the GFP chromophore, it sucks up the energy in the light, it is excited.

In the next phase, the chromophore gets rid of the energy. It emits light, which is now in the green wavelength. In jellyfish, the GFP’s chromophore simply transforms the blue light from aequorin into green light. This is why the jellyfish and aequorin glow in different colors.

What is revolutionary about GFP is that the protein does not need any additives to glow, in contrast to aequorin and other bioluminescent proteins, which require a continuous supply of energy rich molecules. It is enough to radiate GFP with UV light or blue light. The light enters the cells and meets GFP, which glows green. If the researchers had needed to add a chemical, they would have had to inject it into the cell – a process which can both disturb the cell and is difficult to carry out at such microscopic scales.