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MBL Scientist Wins Nobel Prize For Work With Bioluminescence

Posted in: Falmouth News, Top Stories
By CHRISTOPHER KAZARIAN
Oct 10, 2008 - 1:30:12 PM
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Nobel Prize winner Osamu Shimomura of Falmouth listens to a question during Wednesday’s press conference at the Marine Biological Laboratory. The longtime scientist won the prize in chemistry for his discovery of green fluorescent protein, or GFP, in 1961. His work has had direct impacts on modern medicine, helping researchers understand how nerve cells in the brain develop and how cancer cells spread. CHRISTOPHER KAZARIAN/ENTERPRISE
FALMOUTH- “God’s gift comes in strange ways,” Gary G. Borisy, director of the Marine Biological Laboratory, said. To Osamu Shimomura of Falmouth, he said, that gift came in the form of a “glowing jellyfish that had a lot to offer.”
Dr. Shimomura’s discovery of what caused jellyfish to give off that luminescence—the molecule known as green fluorescent protein (GFP)—nearly a half-century ago was “decades ahead of its time,” Dr. Borisy added and has ushered in what he termed “a revolution in cell biology.”
GFP has led to medical breakthroughs in cancer and Alzheimer’s research. And at 5 o’clock on Wednesday morning, Dr. Shimomura was thanked for his contribution to science with a call from the Royal Swedish Academy of Sciences to his Sippewissett Road home informing him that he had won the 2008 Nobel Prize in Chemistry.
When that call came, “I was in a deep sleep,” he said during a press conference six hours later at MBL’s Rowe Building. “My wife answered. She said it was someone from Stockholm. At that moment she knew already.”
As video cameras rolled and bulbs flashed in his face, Dr. Shimomura stood behind a lectern, answering questions from a media contingent that was heavily represented with those from his homeland of Japan. He told them he was taken aback by Wednesday’s announcement. “I was very, very surprised,” he said, explaining that as a biologist, “I was not expecting to receive a chemistry award... My accomplishment was just the discovery of protein.”
“This is unexpected to me, but I am happy,” he added.
Dr. Shimomura will share the prize, which includes a monetary award of $1.4 million, with Martin Chalfie of Columbia University in New York and Roger Y. Tsien of University of California-San Diego. He plans on going to Stockholm with his wife, Akemi, in December to receive his award. The couple have a son, Tsutomu, and a daughter, Sachi.
Born in Kyoto, Japan, in 1928, Dr. Shimomura had his education interrupted by the war as well as the dropping of the atomic bomb. The fallout left his homeland “in terrible shape,” he said. “You have to understand the situation in Japan after the war was a mess.”
As a result, he attributed much of his aptitude for science to self-study as opposed to what he gained from Nagasaki College of Pharmacy, where he graduated in 1951. Having received his diploma from such a small school, he said, is proof that Nobel Prize winners can come from anywhere.
Following his undergraduate work, the Nobel Foundation reported, Dr. Shimomura worked as a research student for Professor Yashimasa Hirata at Nagoya University, from 1955 to 1958, where he was given the task of discovering what made the remains of Cypridina, a crushed mollusk, glow when it was moistened with water.
After discovering that material, which happened to be a protein, and publishing the results of that study, Dr. Shimomura was recruited by Dr. Frank H. Johnson from Princeton University to assist in research on the luminescence of another sea creature, the jellyfish Aequorea victoria.
Before he left for the United States in 1960, Professor Hirata awarded Dr. Shimomura with a PhD from Nagoya University, although he was not enrolled as a doctoral student.
In an article he wrote in 1995, titled “A Short Story of Aequorin,” Dr. Shimomura explained why he accepted Dr. Johnson’s offer to aid in his research. “He asked me if I would be interested in studying the bioluminescence of this jellyfish,” he wrote. “The powder did not emit any light when moistened. But 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’.”
Together, in the summer of 1961, they traveled to Friday Harbor and began collecting jellyfish, cutting off the edges of the creatures with scissors and pressing them through a filter to obtain a liquid called “squeezate.”
The goal, he wrote, was to extract the luminescent substance from the squeezate, which failed initially. It was a painstaking process, he continued, in which he and Dr. Johnson butted heads regarding the manner in which this should be done.
“I spent the next several days soul-searching, trying to imagine the reaction that occurs in luminescing  jellyfish and searching for a way to extract the luminescent principle,” he wrote. “I often meditated on a drifting rowboat under the clear summer sky.”
It is there where Dr. Shimomura conceived that another enzyme, or protein, was most likely involved in the ability of jellyfish to emit light. He was successful in extracting the luminescent substance of jellyfish by mixing a small portion of the squeezate with acidified water, but the actual breakthrough, he wrote, came when he added seawater to the solution.
At that moment, he realized that calcium ions in the seawater caused a chemical reaction, emitting a flash of light that was blue, and thus, different from the green found on the edges of jellyfish.
Bringing back the jellyfish extract from roughly 10,000 specimens to Princeton, the pair were able to isolate the blue luminescent material from the liquid, naming the protein aequorin, after the genus name of the jellyfish.
In their publication on this process, the pair also mentioned they had isolated a protein that was slightly green in sunlight and fluorescent green in ultraviolet light. This was the first description of GFP.
Using his own work as an example, Dr. Shimomura urged young scientists to study something they are passionate about. And even if they face difficulties, he said, they should always make every effort to finish their project. “Don’t give up,” he said.
Dr. Shimomura continued his research on GFP until 1979, he said, and left Princeton University two years later. He arrived at MBL the following year, where he was a senior scientist until 2001. During that same time, his wife was employed as his research assistant.
Since 1988, Dr. Shimomura has been a member of the MBL Corporation and is a senior scientist emeritus at MBL, as well as a professor emeritus at Boston University Medical School.
It was not until 1994, he said, when he fully realized how important his discovery of GFP was.
It was the basis for both Dr. Chalfie’s and Dr. Tien’s research. In 1988, Dr. Chalfie heard about GFP for the first time at a seminar related to bioluminescent organisms at Columbia University. He was able to insert GFP into a roundworm, making it glow green, and thus, proved successful in using the protein as a genetic tag.
Dr. Tien was able to extend GFP beyond green, giving various proteins and cells different colors that has allowed scientists to follow several different biological processes at once. 
“So today, 46 years after Shimomura first wrote about the green fluorescent protein, there is a kaleidoscope of GFP-like proteins which shine with all the colours of the rainbow,” the Royal Swedish Academy of Sciences wrote in a press release.
Dr. Shimomura’s discovery gave scientists the ability to produce yellow, cyan, and red in the nerve cells of the brains in mice, resulting in an experiment called “the brainbow,” allowing researchers to follow nerve fibers in individual cells.
His work, Dr. Borisy said, “is fundamental biology.... Previously, we had no way of identifying individual molecules in living cells. That is why this is important.”
In a phone interview yesterday afternoon, Dr. John W. Rowe, chairman of the board for the MBL and a professor at Columbia University, said that this year’s prize “is a striking example of the capacity of basic research on marine organisms to yield important information regarding human disease.”
This award, he said, makes the work being done at MBL relevant to the casual observer. “It demonstrates the potential for basic biological discoveries, whether looking at marine organisms or not, to yield insights and tools that can be productively applied to the study of disease,” he said.
In addition, he said, Dr. Shimomura’s research is proof that research does not need expensive machinery or million dollar grants to be significant. “His was amazingly fundamental and basic,” he said. “It lets young people know they have a chance.”
While Dr. Shimomura is the latest Nobel Prize winner, he is by no means the first for the MBL. The Woods Hole institution has had 56 Nobel scientists, some more transient and others long-term staff, pass through its halls since its founding in 1888.
Since 1901, the Nobel Prize for Chemistry has been awarded to 153 individuals. The Nobel Foundation also distributes prizes in literature, physics, medicine, economics, and peace.